pdfMRC NIMR Annual Report - The Francis Crick Institute
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pdfMRC NIMR Annual Report - The Francis Crick Institute
2012/2013 Annual Report and Prospectus MRC National Institute for Medical Research Science for health Edited by:Victor Tybulewicz Designed by: Joe Brock Photography by: Neal Cramphorn & James Brock Production: Christina McGuire & Frank Norman Editorial Assistant: Eileen Clark © MRC National Institute for Medical Research Enquiries about this report should be addressed to: %WWMWXERX(MVIGXSV´W3J½GI +44 (0)20 8816 2281 [email protected] Further information is available on our website at: http://www.nimr.mrc.ac.uk Copies obtainable from the Librarian at NIMR ISBN-13: 978-0-9572625-1-5 MRC National Institute for Medical Research 2012/2013 Annual Report and Prospectus Contents Director’s foreword The Francis Crick Institute Science overview 7GMIRXM½G,MKLPMKLXW 2-16LMWXSV]ERHQMPIWXSRIW Careers : PhD students Sandwich students and work experience 4SWXHSGXSVEPWGMIRXMWXW 4VSKVEQQI0IEHIVW Research support %RMQEP8IGLRMGMERW 8VERWPEXMSREPVIWIEVGL 7YTTSVXJSVXVERWPEXMSR 'SQQIVGMEPXVERWPEXMSR 'PMRMGEPXVERWPEXMSR 4YFPMGSYXVIEGL 6IWIEVGLKVSYTW Infections and Immunity /EXI&MWLST6IXVSZMVEPMRJIGXMSRERHVITPMGEXMSR 1MOI&PEGOQER 1EPEVMETEVEWMXIIKVIWWERHMRZEWMSR 0YM^4IHVSHI'EVZEPLS1XFW]WXIQWERHGLIQMGEPFMSPSK] .SLR(SSVFEV ,YQERTETMPPSQEZMVYW (IPQMVS*IVRERHI^6I]IW'LMPHLSSHWIZIVIQEPEVME )ZE*VMGOIP %RXMToxoplasma gondii immunity 1E\+YXMIVVI^ 'IPPFMSPSK]SJ1XFMRJIGXMSR 8SR],SPHIV1EPEVMETEVEWMXIWERHVIHFPSSHGIPPW +ISVKI/EWWMSXMW %RXMZMVEPMQQYRMX] .IER0ERKLSVRI -QQYRMX]MRQEPEVMEMRJIGXMSRW 7XIZI0I]6IKYPEXMSRSJMQQYRIVIWTSRWIW .SLR1G'EYPI] ,SWXWTIGM½GMX]SJMR¾YIR^EZMVYWIW %RRI3´+EVVE6IKYPEXMSRSJXLIMQQYRIVIWTSRWI :IRM^IPSW4ETE]ERRSTSYPSW2IYXVSTLMPQIHMEXIHMQQYRIHIJIRWI &IRIHMGX7IHHSR6IKYPEXMSRSJ8GIPPLSQISWXEWMW +MXXE7XSGOMRKIV 8GIPPGSQTEVXQIRXW .SREXLER7XS]I 6IXVSZMVYWLSWXMRXIVEGXMSRW 4EZIP8SPEV%GXMZEXMSRSJMQQYRIVIGITXSVW :MGXSV8]FYPI[MG^ 0]QTLSG]XIWMKREPXVERWHYGXMSR %RHVIEW;EGO -QQYRIVIWTSRWIXSMR¾YIR^E 6SFIVX;MPOMRWSR ,-:EWWSGMEXIHXYFIVGYPSWMW 1EVO;MPWSR6IKYPEXMSRSJ8LGIPPW (SYKPEW=SYRK 1]GSFEGXIVMEPTEXLSKIRIWMW ;,3'SPPEFSVEXMRK'IRXVIJSV6IJIVIRGIERH6IWIEVGLSR-R¾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artin Webb Mechanisms of motor proteins Neurosciences (MQMXVMSW%REWXEWMSY'ERGIVQIXEFSPMWQ 7MI[0ER%RK2IYVSREPWYFX]TIWTIGM½GEXMSR 2 MRC National Institute for Medical Research 4 6 8 10 14 16 19 31 34 35 36 38 39 40 41 43 44 45 46 48 49 50 51 53 54 55 56 58 59 60 61 63 64 65 66 68 69 (IRMW&YVHEOSZ &VEMRERHQIXEFSPMGSVGLIWXVEXMSR %PI\+SYPH6IKYPEXMSRSJKVS[XLERHQIXEFSPMWQ *VERpSMW+YMPPIQSX %REP]WMWSJRIYVSKIRIWMW 8VS]1EVKVMI7IRWSV]TVSGIWWMRKMRWMRKPIGIPPW :EWWMPMW4EGLRMW (IZIPSTQIRXSJXLIRIVZSYWW]WXIQ -VMW7EPIGOIVDrosophilaZMWYEPGMVGYMXEWWIQFP] (EZMH;MPOMRWSR &SYRHEV]JSVQEXMSRERHRIYVSKIRIWMW +IRIXMGWERH(IZIPSTQIRX James Briscoe Pattern formation in the CNS 4EYP&YVKS]RI =GLVSQSWSQIERHMRJIVXMPMX] +VIK)PKEV 6IKYPEXMSRSJIEVP]HIZIPSTQIRX 1MOI+MPGLVMWX +IRIVIKYPEXSV]RIX[SVOW 1EPGSPQ0SKER0MQFHIZIPSTQIRX 6SFMR0SZIPP&EHKI7I\WXIQGIPPWERHGIPPJEXI 8MQ1SLYR,IEVXHIZIPSTQIRXMRZIVXIFVEXIW %RHVI[3EXIW)QFV]STEXXIVRMRK )POI3FIV0MZIVHIZIPSTQIRXMR^IFVE½WL Jim Smith Mesoderm formation 4IXIV8LSVTI7]WXIQWQMGVSWGST]SJGIPPJEXI James Turner X chromosome inactivation .IER4EYP:MRGIRX4EXXIVRMRKERHLSQISWXEWMW 0]PI>MQQIVQER *VSKKIRIXMGW 6IWIEVGLJEGMPMXMIW &MSPSKMGEPERH4VSGIHYVEP7IVZMGIW 16'&MSQIHMGEP216'IRXVI <VE]GV]WXEPPSKVETL] Mass spectrometry 4VSXIMRWIUYIRGIEREP]WMWERHWXVYGXYVIQSHIPPMRK %REP]XMGEPYPXVEGIRXVMJYKEXMSR 'SRJSGEPMQEKMRKERHEREP]WMW ,MWXSPSK] )PIGXVSRQMGVSWGST] 348ERH,6)1MQEKMRK 7MRKPIQSPIGYPIXIGLRMUYIW )PIGXVSRGV]SQMGVSWGST] Bioresources Genomics *PS[G]XSQIXV] 0IZIPLMKLGSRXEMRQIRXZMVYWPEFSVEXSV] Insectary )PIGXVSRMGMRWXVYQIRXTVSXSX]TMRKERHWYTTSVX 1IGLERMGEP)RKMRIIVMRK *EGMPMXMIWERH-RJVEWXVYGXYVI7IVZMGIW PhotoGraphics 'SQTYXMRKERH8IPIGSQQYRMGEXMSRW 0MFVEV]MRJSVQEXMSR GSQQYRMGEXMSRW Web Team +IRIVEPWIVZMGIW -RWXMXYXIQEREKIQIRX 2SFIP0EYVIEXIW *MZIJEQSYWEPYQRM In memoriam 7GMIRXM½GWIQMREVW 7XEJJLSRSYVW PhD theses awarded MRC centenary award winners 'YVVIRXJYRHMRKWSYVGIW &MFPMSKVETL] 2-163(WSGMEPGPYF Research themes index Index 1ETPSGEXMSRERHXVEZIP 80 81 83 84 85 86 88 89 90 91 93 94 95 96 98 99 101 104 105 106 108 109 110 111 113 114 115 116 118 119 130 133 134 139 140 143 144 145 146 160 164 inside back cover MRC National Institute for Medical Research 3 Director’s foreword -XLEWFIIRERSXLIVZIV]FYW]]IEV[MXL]IXQSVIKVIEXWGMIRGIWII7GMIRXM½G,MKLPMKLXWSRTEKIWERHMRVIWTSRWIXSSYV VIGIRXUYMRUYIRRMEPVIZMI[[ILEZIVIGVYMXIHERYQFIVSJI\GIPPIRXWGMIRXMWXWXSIWXEFPMWLRI[VIWIEVGLTVSKVEQQIW :IRM4ETE]ERRSTSYPSW[SVOIHMR%VXYVS>]GLPMRWO]´WPEFEXXLI1E\4PERGO -RWXMXYXIJSV-RJIGXMSR&MSPSK]MR&IVPMR[LIVILIWXYHMIHXLIJSVQEXMSRSJ RIYXVSTLMPI\XVEGIPPYPEVXVETW2)8W%X2-16LIMWWXVMZMRKXSYRHIVWXERHXLI QSPIGYPEVQIGLERMWQWXLEXHVMZI2)8VIPIEWIERHJYRGXMSRHYVMRKMRJIGXMSR ERHHMWIEWIYWMRKLYQERRIYXVSTLMPWERHQSYWIQSHIPW1E\+YXMIVVI^WTIRX XLVII]IEVW[SVOMRKSRQ]GSFEGXIVMEPTLEKSWSQIH]REQMGWMR+EVIXL+VMJ½XLW´ PEFEX)1&0,IMHIPFIVKXLIRPIHEKVSYT[SVOMRKMRTLEKSWSQIFMSPSK]EXXLI ,IPQLSPX^'IRXVIJSV-RJIGXMSR6IWIEVGLMR&VEYRWGL[IMK+IVQER],MWRI[PEFEX 2-16[MPPTVSZMHIMRWMKLXWMRXSXLIQSPIGYPEVQIGLERMWQWF][LMGLM. tuberculosis QERMTYPEXIWXLITLEKSWSQEPIRZMVSRQIRXERHEZSMHWOMPPMRKF]TLEKSG]XIWERH LS[LSWXTLEKSG]XIWIPMQMREXIQ]GSFEGXIVME Veni Papayannopoulos (left) and Max Gutierrez (right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enis Burdakov Dimitris Anastasiou Andy Oates -[EWTPIEWIHXLEX8VS]1EVKVMI[EWGSR½VQIHEW,IEHSJXLI(MZMWMSRSJ2IYVSTL]WMSPSK]ERHXLEXLI[MPPLIPTHVMZISYV IJJSVXWXSI\TERHRIYVSWGMIRGI[MXLMR2-16;I[IVIEPWSHIPMKLXIHXLEX.EQIW&VMWGSIERH:MGXSV8]FYPI[MG^[IVIFSXL KVERXIH;IPPGSQI8VYWX7IRMSV-RZIWXMKEXSV%[EVHWJSVXLIMV[SVOVIWTIGXMZIP]SRXLIHIZIPSTQIRXSJXLIWTMREPGSVHERHSR (S[RW]RHVSQI:MGXSV´W[SVOSR(S[RW]RHVSQIMWEPWSVIGIMZMRKWYTTSVXJVSQE;IPPGSQI8VYWX7XVEXIKMG%[EVHXLVSYKL XLI0SR(S[RW'SRWSVXMYQ%RHMREHHMXMSRXSQER]SXLIVKVERXW2-16[EWEFPIXSWYTTSVXEPEVKIRYQFIVSJMXWIEVP]GEVIIV VIWIEVGLIVWYRHIVXLI16''IRXIREV])EVP]'EVIIV%[EVHWWGLIQI-WLSYPHTEVXMGYPEVP]PMOIXSGSRKVEXYPEXI4IXIV8LSVTI 4VSKVEQQI0IEHIV8VEGO0EWWI7XEGL4SWXHSG/EX'SPPMRWERH,EVEPH,EVX[IKIV4L(WXYHIRXWERH'PEVI(EZ]8VEMRMRKERH 8VEZIP%[EVH 4 MRC National Institute for Medical Research (top row) Peter Thorpe, Lasse Stach and Kat Collins (bottom row) Harald Hartwegger and Clare Davy 2-16´WMRXIVHMWGMTPMREV]ETTVSEGLXSFMSQIHMGEPWGMIRGI[EWWXVIRKXLIRIHF]XLIJSVQEXMSRSJE5YERXMXEXMZI&MSPSK]-RXIVIWX +VSYT6YRF]1MGLEIP'SLIRXLMWFVMRKWXSKIXLIVVIWIEVGLIVWYWMRKUYERXMXEXMZIXIGLRMUYIWERHGSQTYXEXMSREPQIXLSHWXS WSPZIFMSPSKMGEPTVSFPIQW8LI-RWXMXYXI´W,MKL8LVSYKLTYX)\TIVMQIRXEP8IGLRMUYI-RXIVIWX+VSYTVYRF]%FHYP7IWE]LEWFIIR [MHIRIHXSMRGPYHIWGMIRXMWXWJVSQ'69/´W0SRHSR6IWIEVGL-RWXMXYXIERHJVSQSXLIVTEVXRIVWMRXLI*VERGMW'VMGO-RWXMXYXI %PXLSYKL2-16[MPPFIQSZMRKXSXLI*VERGMW'VMGO-RWXMXYXIMREJI[]IEVWSYVVIWIEVGLVIQEMRWEXXLILMKLIWXPIZIP%W[IPPEW VIGVYMXMRKRI[VIWIEVGLIVWFY]MRKRI[IUYMTQIRXJSVXLIQERHVIJYVFMWLMRKXLIMVPEFWTEGI[ILEZIFYMPXERI[MRWIGXEV]EW TEVXSJ.IER0ERKLSVRI´WPEFSVEXSV]MRXLI(MZMWMSRSJ4EVEWMXSPSK]8LMW[MPPJEGMPMXEXIXLIFVIIHMRKSJQSWUYMXSIWXSI\TPSMXVSHIRX QSHIPWJSVXLIEREP]WMWSJQEPEVMEMRLYQERW;ILEZIEPWSGVIEXIHERI[WIQMREVVSSQJVSQWTEGIVIPIEWIHF]XLI0MFVEV]ERH XLIQEMR0MFVEV]VIEHMRKVSSQLEWFIIRVIGSR½KYVIHXSTVSZMHIEHHMXMSREPMRJSVQEPQIIXMRKERHGSPPEFSVEXMSREVIEW 7IZIVEPQIQFIVWSJWXEJJPIJXHYVMRK6MXE'LEMWGSRXMRYMRKLIV[SVOSRIYOEV]SXMGGLVSQSWSQIQIXEFSPMWQMR7YWWI\ ERH)H,YPQILEWVIXMVIHEJXIVVYRRMRKEKVSYTEX2-16JSV]IEVW)H´WTMSRIIVMRK[SVOSRXLIWXVYGXYVIERHJYRGXMSRSJ+ TVSXIMRGSYTPIHVIGITXSVWLEWFIIRZIV]MR¾YIRXMEPERHMX[EWETPIEWYVIXSLIEVLMWVIGIRX1MPP,MPP0IGXYVI[LMGLWYQQEVMWIH 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%RSXLIVMRXIVHMWGMTPMREV]GSPPEFSVEXMSRWE[%PI\+SYPH[SVOMRK [MXL'PEYHI0IGLIRIJVSQ,EVZEVH1IHMGEP7GLSSPXSETTP] QYPXMMWSXSTIMQEKMRKQEWWWTIGXVSQIXV]1-17XSXLIEREP]WMW SJPMTMHQIXEFSPMWQ8LI]HIZIPSTIHEQIXLSHXLEXEPPS[IH XLIQXSZMWYEPMWIERHUYERXMXEXIWIZIVEPHMJJIVIRXEWTIGXWSJ QIXEFSPMWQ[MXLERMQTVIWWMZIPIZIPSJWTEXMEPVIWSPYXMSR° I\GIIHMRKXLEXSJXLIPMKLXQMGVSWGSTI8LIQIXLSHQEOIWMX TSWWMFPIXSEHHVIWWMQTSVXERXFMSPSKMGEPERHQIHMGEPUYIWXMSRW EXXLIMRXIVJEGIFIX[IIRQIXEFSPMWQERHGIPPFMSPSK] Rapid lipid turnover in Drosophila intestinal cells after a13C-palmitate pulse-chase. 1EMRXEMRMRKXLIMRXIVHMWGMTPMREV]XLIQI.EQIW 8YVRIV[SVOIH[MXL+VIK)PKEV1MOI+MPGLVMWXERH ;MPPMI8E]PSVXSMHIRXMJ]XLIKIRIVIWTSRWMFPIJSV <GLVSQSWSQIMREGXMZEXMSRMRXLIWIGSRHPEVKIWX GPEWWSJQEQQEPWXLIQIXEXLIVMERWQEVWYTMEPW< GLVSQSWSQIMREGXMZEXMSRSGGYVWMRQSWXQEQQEPW ERHMWMQTSVXERXXSSYVYRHIVWXERHMRKSJQER] HMJJIVIRXHMWIEWIW*SVI\EQTPIEFRSVQEPMXMIWMR< chromosome inactivation have been associated with FSXLQIRXEPVIXEVHEXMSRERHGERGIV Discovery of a candidate X-inactivating RNA in the opossum. MRC National Institute for Medical Research 11 7GMIRXM½GLMKLPMKLXW 8[SSXLIVTMIGIWSJVIWIEVGL[MXLVIPIZERGI XSGERGIVGEQIJVSQSYVWXVYGXYVEPFMSPSKMWXW %RHVIW6EQSW[SVOMRK[MXLXLI16' &MSQIHMGEP216'IRXVIERHGSPPIEKYIWEX XLI-XEPMER'ERGIV-RWXMXYXIMR+IRSEHMWWIGXIH XLIQSPIGYPEVTEXL[E]XLEXVIKYPEXIWPIXE QMGVS62%XLEXEGXWEWEXYQSVWYTTVIWWSV-R TEVXMGYPEVXLI]HI½RIHXLI[E]MR[LMGLXLI MRHMZMHYEP/,HSQEMRWSJXLITVSXIMR/764E TSWMXMZIVIKYPEXSVSJPIXFMSKIRIWMWMRXIVEGX [MXLXLIPIXQM62%TVIGYVWSV 7XIZI7QIVHSRMRGSPPEFSVEXMSR[MXL*YQMOS )WEWLMMR3\JSVHLEWVIZIEPIHRI[PMROW FIX[IIR(2%HSYFPIWXVERHIHFVIEOVITEMV ERHXLIGIPPG]GPIQEGLMRIV]8LI]WLS[IH XLEX4SPSPMOIOMREWI4PO[LMGLMWVIUYMVIH JSVGIPPTVSPMJIVEXMSRERHMWJVIUYIRXP]YT VIKYPEXIHMRGERGIVGIPPWTLSWTLSV]PEXIW 6EHVIGSQFMREWIHYVMRKXLIGIPPG]GPIERH MRVIWTSRWIXS(2%HEQEKI8LI½RHMRKW VITVIWIRXEWMKRM½GERXWXITXS[EVHE GSQTVILIRWMZIYRHIVWXERHMRKSJXLIGSRXVSP SJLSQSPSKSYWVIGSQFMREXMSRF]GIPPG]GPI VIKYPEXSVW4IVLETWQSWXMQTSVXERXMWXLI MQTPMGEXMSRXLEXMRLMFMXSVWSJ4POEPVIEH] E[IPPZEPMHEXIHERXMGERGIVXEVKIXQE]EGX W]RIVKMWXMGEPP]XSTVSZMHIMRGVIEWIHIJ½GEG] EKEMRWXFVIEWXERHSZEVMERGERGIVERHTIVLETW 12 MRC National Institute for Medical Research In KH3 recognition of the miRNA precursor the RNA G4 makes Watson-Crick-like contacts with the protein backbone and side chains (Andres Ramos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½VWXGPMRMGEPMRZIWXMKEXMSR MRXSXLIMQQYRSQSHYPEXSV]EGXMSRWSJin vivo ZMXEQMR(WYTTPIQIRXEXMSRHYVMRKXVIEXQIRX SJERMRJIGXMSYWHMWIEWI*MREPP]%RRI3´+EVVE [SVOIH[MXL.IER0ERKLSVRIERHLIVKVSYTXS ½RHXLIWSYVGISJEGVMXMGEPQSPIGYPIXLEXLIPTW GSRXVSPMQQYRIQIHMEXIHTEXLSPSK]MRQEPEVME 8LIWI½RHMRKWEVISJVIEPMQTSVXERGIJSVXLI QEPEVME½IPHEWXLI]HI½RIXLIGVMXMGEPGIPPYPEV WSYVGISJTVSXIGXMZI-0ERHXLITEXL[E]W PIEHMRKXSMXWTVSHYGXMSR8LMWORS[PIHKIQMKLX FIMQTSVXERXJSVXLIIWXEFPMWLQIRXSJTVSXSGSPW JSVQERMTYPEXMSRSJXLIWITEXL[E]WMRSVHIVXS TVIZIRXWIZIVIQEPEVMEMRLYQERW A model for Rad51 recruitment mediated through sequential phosphorylation by Plk1 and casein kinase 2 (CK2).(Steve Smerdon) References %RKIPSIXEPNature 488,¯ 0STIWIXEPPNAS 109 &EPEWOEWIXEPCell, 148 7XIMRLEYWIVIXEPNature481,¯ +VERXIXEPNature 487¯ 2MGEWXVSIXEPNature Structural & Molecular Biology 19,¯ =EXEIXEPMolecular Cell 45¯ =SYRKIXEPNature 491,¯ 'SYWWIRWIXEPPNAS 109 *VIMXEHS6SWEVMSIXEPJournal of Immunology, 188 MRC National Institute for Medical Research 13 NIMR history and milestones 1933 Discovery of flu virus Christopher Andrewes, Patrick Laidlaw and Wilson Smith first isolated the human influenza virus. 1957 Interferon 1951 Steroid biosynthesis John Cornforth 1940 1950 1952 Gas chromatography After receiving the Nobel Prize in 1950 for his earlier discovery of partition chromatography, Archer Martin joined NIMR and with A.T James he developed gas chromatography, a technique now widely used in laboratories and the chemical industry. 1936 The role of acetylcholine as a neurotransmitter Henry Dale established the chemical basis of neurotransmission and the role of acetylcholine as a neurotransmitter, receiving the Nobel Prize for this work in 1936. 14 MRC National Institute for Medical Research John Skehel revealed the structure of influenza virus proteins involved in the infection of cells, for which he was awarded the Louis-Jeantet Prize for Medicine in 1988. This work opened new perspectives for the design of antiviral drugs. 1960s Cryobiology Audrey Smith discovered how to store biological material at low temperature, pioneering techniques for the freezing of sperm, blood, bone marrow, corneas and many other tissues. completed the first total synthesis of the non-aromatic steroids and identified the chemical structure of cholesterol. He received the Nobel Prize in 1975. 1930 1981 Structure of influenza haemagglutinin Alick Isaacs discovered interferon, a factor that can transfer a virus-resistant state to cells that had not been infected, and is now used to treat many infections and cancers. 1960 1970 1986 Globin locus control region Frank Grosveld discovered regulatory sequences that govern expression of the globin gene cluster, and that confer a copy number dependent level of transgenic gene expression. He was awarded the Louis-Jeantet Prize for Medicine in 1991. 1980 1973 Long-term potentiation Tim Bliss and Terje Lømo discovered the phenomenon of synaptic long-term potentiation, one of the main mechanisms by which the brain learns and remembers. 1958 Immunoglobulin structure Rodney Porter was given the Nobel Prize in 1972 for the discovery of the structure of immunoglobulins. The work increased understanding of the immune system and led to novel approaches to diagnosis and therapy. 1989 Hox gene colinearity Robb Krumlauf showed that the linear relationship between the organisation of Hox genes along the chromosome and their expression along the head-to-tail axis is conserved in vertebrates. 1993 Mesoderm-inducing factor 2005 Mouse model of Down syndrome Jim Smith discovered that activin is a mesoderm-inducing factor, opening up understanding of how signalling factors control the formation of tissues during embryo development. Victor Tybulewicz created a genetically manipulated mouse that carries almost all of human chromosome 21. The resulting strain of mice has become a valuable tool in research on Down syndrome. 2010 Transcriptome signature in human tuberculosis Anne O’Garra discovered a novel transcriptomic signature that provides insights into fundamental pathogenesis of tuberculosis and has application to the development of improved diagnostic tools. 1996 Discovery of the anterior organising centre 2007 AMP-activated protein kinase (AMPK) structure Rosa Beddington discovered a novel signalling centre in the mouse embryo required for correct formation of the head-to-tail axis during embryonic development. Steve Gamblin determined the structure of the enzyme that regulates cellular energy levels, AMPK. The discovery paves the way for better treatments of Type 2 diabetes. 1990 2000 2010 1999 Eph receptors mediate cell segregation 2007 Malaria release mechanism David Wilkinson uncovered a new mechanism that maintains the correct organisation of tissues, mediated by signalling through Eph receptors and ephrins. Mike Blackman identified an enzyme that triggers release of the malaria parasite from infected red blood cells thereby enabling it to invade new cells. The enzyme is a new target for improved anti-malarial drug design. 1991 The sex determining gene Robin Lovell-Badge showed that the presence of the Sry gene on the Y chromosome is sufficient to cause the embryonic gonad to develop as testis rather than ovary. He received the Louis-Jeantet Prize for Medicine in 1995. 2006 Discovery of Th17 subset Gitta Stockinger defined the developmental steps that lead to the Th17 immune response. Th17 cells are important in the pathogenesis of many autoimmune diseases. MRC National Institute for Medical Research 15 CAREERS PhD students 8LIXVEMRMRKSJWXYHIRXWSJEPPPIZIPWMWMRXIKVEPXS2-16ERHXLVSYKLXLITVSKVEQQIW[ISJJIV[IWXVMZIXSXVEMRFMSQIHMGEP PIEHIVWSJXLIJYXYVI PhD Programme 8LI2-16JSYV]IEV4L(TVSKVEQQILEWFIIRHIWMKRIHXSIUYMTSYVWXYHIRXW [MXLXLIWGMIRXM½GERHXVERWJIVEFPIWOMPPWVIUYMVIHXSQEOIXLIQGSQTIXMXMZIEXXLI LMKLIWXPIZIPFSXLREXMSREPP]ERHMRXIVREXMSREPP]*YPP]MRXIKVEXIHMRXSXLI2-164L( TVSKVEQQIEVIQIHMGEPYRHIVKVEHYEXI1&&7WXYHIRXW[LSNSMRYWMR.ERYEV] IEGL]IEVZMEXLI9'01&4L(TVSKVEQQI%PPSJSYVWXYHIRXWFIRI½XJVSQEGGIWW XSXLIWXEXISJXLIEVXJEGMPMXMIWERHI\XIRWMZII\TIVXMWIEZEMPEFPIEGVSWWXLI-RWXMXYXI ;IIRGSYVEKIMRRSZEXMSRMRXIVHMWGMTPMREVMX]ERHGSPPEFSVEXMSRERHMRHIIHQER] SJSYV4L(WXYHIRXWLEZITVSNIGXW[LMGLWTERQYPXMTPIVIWIEVGLXLIQIWTVSZMHMRK XLIQ[MXLERI\GIPPIRXSTTSVXYRMX]XSFVSEHIRXLIMVKIRIVEPYRHIVWXERHMRK SJWGMIRGIERHTVEGXMGEPI\TIVXMWI%WEVIWYPXSJXLMWSYVSVWSWXYHIRXW WMKRM½GERXP]GSRXVMFYXIXSXLIVIWIEVGLSYXTYXSJ2-16 3REVVMZEPEX2-16WXYHIRXW[SVOGPSWIP][MXLXLIMVWYTIVZMWSVWXSHIZIPSTXLIMV TVSNIGXTVSTSWEPXLI]EPWSGLSSWIEXLIWMWGSQQMXXIIQIQFIVWSJ[LMGLLEZI I\TIVXMWIMREVERKISJWGMIRXM½GEVIEW[LS[MPPEHZMWIXLIWXYHIRXJSVXLIHYVEXMSR SJXLI4L(8SWYTTSVXXLIHIZIPSTQIRXSJSYVWXYHIRXW[ISJJIVE[MHIVERKISJ MRXIVREPXVEMRMRKGSYVWIWVERKMRKJVSQFMSMRJSVQEXMGWWXEXMWXMGWERHQMGVSWGST]XS IXLMGWVITSVXTVITEVEXMSRERHTVIWIRXEXMSRWOMPPW;IEPWSVYREWIVMIWSJGEVIIVW WIQMREVWERHERERRYEPGEVIIVWVSYRHXEFPIIZIRX[LMGLVI¾IGXXLIFVSEHVERKISJ GEVIIVWEZEMPEFPIXS4L(W Donna Brown Director of Studies ;IIRGSYVEKIEKSSH[SVOPMJIFEPERGIERH]SY´PP½RHEVERKISJWSGMEPEGXMZMXMIW LIVIMRGPYHMRKJSSXFEPP½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½XJVSQSYVGPSWI VIPEXMSRWLMT[MXLSYV'VMGOTEVXRIVWIWTIGMEPP]XLI'69/0SRHSR6IWIEVGL-RWXMXYXI 16 MRC National Institute for Medical Research CAREERS The 2012 intake of PhD students Student representatives 8LIWXYHIRXVITVIWIRXEXMZIWJSVQMRXIKVEPPMROWFIX[IIRXLI student body and various parts of the Institute and the wider GSQQYRMX]8LI]TVMQEVMP]WIVZIXLIWXYHIRXWF]QEOMRKWXYHIRX opinions heard on a number of key committees within the -RWXMXYXIMRGPYHMRKXLI)XLMGEP8VEHI9RMSRERH'SQQYRMGEXMSR GSQQMXXIIWXSREQIFYXEJI[%HHMXMSREPP]VITVIWIRXEXMZIW EMQXSMRWTMVIEWIRWISJGSQQYRMX]EQSRKWXXLIWXYHIRXWF] SVKERMWMRKVIKYPEVQIIXMRKWERHWSGMEPEGXMZMXMIW;IIOP]WXYHIRX WIQMREVWI\TSWIWXYHIRXWXSXSTMGWSYXWMHISJXLIMVTVMQEV]½IPH SJMRXIVIWXERHEPPS[WXYHIRXWXSVIGIMZIMRJSVQEPJIIHFEGOSR XLIMVTVIWIRXEXMSRWXSEWOUYIWXMSRWERHXSIWXEFPMWLTSXIRXMEP GSPPEFSVEXMSRW[MXLSXLIV(MZMWMSRW3RISJXLIGLMIJEMQWSJXLMW ]IEV´WGSQQMXXII[MPPFIXSIEWIMRXIKVEXMSRSJWXYHIRXWJVSQ SXLIVGSRWXMXYIRXMRWXMXYXIWSJXLI'VMGOF]GSSVKERMWMRKWSGMEP IZIRXWERHMQTSVXERXP]EREPPWXYHIRXW]QTSWMYQ[LMGL[MPPEPPS[ WXYHIRXWXLISTTSVXYRMX]XSTVIWIRXXLIMV[SVOMREJSVQEPTIIV IRZMVSRQIRX The 2012 student representatives: Martin Carkett, Jimena Anderson, Andy Howe, Alex Eve 2012 Travel Prize )EGL]IEV2-16E[EVHWE8VEZIP4VM^IJSVXLIFIWX YTKVEHIVITSVXERHEVYRRIVYTTVM^ISJE%QE^SRZSYGLIV 8LITVM^IW[IVITVIWIRXIHF]7XIZI+EQFPMR(MVIGXSV SJ6IWIEVGLXSXLI[MRRIV0YG]4EPQIV(IZIPSTQIRXEP &MSPSK]ERHXLIVYRRIVYT7IER'SRWXEFPI(IZIPSTQIRXEP 2IYVSFMSPSK] MRC National Institute for Medical Research 17 CAREERS PhD students – in their own words Lucy Palmer “I have been a PhD student at NIMR for two years, working in the lab of JeanPaul Vincent in the Division of Developmental Biology. I am developing novel in vivo methods to determine the secretory route that Wingless (the main Drosophila Wnt) takes out of the cell in order to move into the extracellular space and signal at a distance from its source. Proteins in the Wnt family are often misregulated in cancers, therefore insights into the movement of these proteins during normal development are essential to better understand the mechanisms involved in tumourigenesis. I was drawn to NIMR due to the world-renowned research and incredible facilities that the Institute is able to offer. Of particular relevance to my project is the Confocal Imaging and Analysis Laboratory (CIAL) that has provided invaluable assistance and advice. The atmosphere at NIMR is highly interactive FSXLWGMIRXM½GEPP]FIX[IIRZEVMSYWPEFSVEXSVMIWERH(MZMWMSRWERHMRWSGMEP situations such as the bar and the 8-a-side football league. This creates a highly supportive and exciting environment for students to undertake their PhD. “ Matteo Villa “I’ve just started my second year of PhD in the Division of Molecular Immunology, funded by a Boehringer Ingelheim Fonds PhD Fellowship. My project aims at investigating the role of the transcription factor Aryl Hydrocarbon Receptor in B cell-mediated immunity. The reasons why I chose NIMR for my PhD is the outstanding quality of research performed and the VITYXEXMSRSJXLI-RWXMXYXI%JXIVSRI]IEVEX2-16-GERHI½RMXIP]WE]XLEXRSX SRP]XLIWGMIRXM½GZEPYIFYXEW[IPPXLIGSPPEFSVEXMZIERHJVMIRHP]IRZMVSRQIRX at the Institute makes the difference. Moreover the training programme for the PhD students and the daily lectures and seminars are strongly contributing to HIZIPSTQ]WGMIRXM½GWOMPPW%PPXLIWIXLMRKWQEOI2-16ERI\GIPPIRXTPEGIJSV 4L(XVEMRMRKFSXLMRXIVQWSJWGMIRXM½GERHTIVWSREPI\TIVMIRGI² 18 MRC National Institute for Medical Research CAREERS Sandwich students and work experience Sandwich placements 2S[QSVIWSXLERIZIVFIJSVILEZMRKTVEGXMGEPVIWIEVGL I\TIVMIRGIMWIWWIRXMEPJSVEWGMIRXM½GGEVIIVEXER]PIZIP 3YVWERH[MGLTPEGIQIRXWTVSZMHIWXYHIRXW[MXLXLI STTSVXYRMX]XSJYPP]MQQIVWIXLIQWIPZIWMREVIWIEVGL PEFJSVQSRXLWERH[SVOSRERMRHITIRHIRXVIWIEVGL TVSNIGX7ERH[MGLWXYHIRXWEPWSLEZIEGGIWWXSE[MHI VERKISJPIGXYVIWWIQMREVERHXVEMRMRKERHXLYWJYPP] FIRI½XJVSQEPPXLEX2-16LEWXSSJJIV1ER]SJSYV WERH[MGLWXYHIRXWKSSRXSHSE4L(EX2-16ERHSXLIV PIEHMRKVIWIEVGLMRWXMXYXMSRW Work experience The 2012 intake of Sandwich students ;IIRGSYVEKIWXYHIRXWJVSQERIEVP]EKIXSXEOIERMRXIVIWXMRWGMIRGI)EGL]IEVPSGEPWGLSSPWXYHIRXW[SVOEPSRKWMHISYV VIWIEVGLIVWUYMXISJXIR4L(WXYHIRXWJSVTIVMSHWSJYTXSWM\[IIOWEPWSWII6IWIEVGL7YQQIV7GLSSPSRTEKI1ER]SJ XLIWIWXYHIRXWGSQIFEGOEWYRHIVKVEHYEXI7YQQIVSV7ERH[MGLWXYHIRXW Alice Mitchell “My Sandwich placement at NIMR offered me a fantastic opportunity to experience lab life – not only the experimental part, but also the interactions within the lab, and it showed me how much fun lab life can be! I chose to do my placement at NIMR as it offered me a chance to carry out research that was really interesting and in a very friendly environment, as well as having the EHZERXEKISJFIMRKMR0SRHSR-PIEVRXPSXWSJWOMPPWVERKMRKJVSQWI\MRK¾MIWXS(2%GPSRMRKJSV Q]TVSNIGXSRVIQSZMRKWTIGM½GKIRIWERHVITPEGMRKXLIQ[MXL¾YSVIWGIRXTVSXIMRWKMZMRKQI MRZEPYEFPII\TIVMIRGIJSVQ]½REP]IEVEXYRMZIVWMX]ERHFVMRKMRKQIXSQ]HIGMWMSRXSETTP]JSVE 4L(3ZIVEPP-LEHEFVMPPMERXI\TIVMIRGIEX2-16ERHEQZIV]KPEH-HMHQ]7ERH[MGL]IEVLIVI² Ben Golland “It can be rare when doing work experience that you really get out of it what you were originally looking for. University courses only give you a small amount of time in the lab and I wanted to feel more comfortable when undertaking experiments. Working in Mike Blackman’s lab over the WYQQIVFVSYKLXQIGSR½HIRGIMRQ]PEFWOMPPW[LMGL-[SYPHSXLIV[MWILEZIRSXLEH%W-´ZINYWX started a year placement for GlaxoSmithKline, the head start has meant I understand the work I’m HSMRKFIXXIVERHEQQYGLQSVIXMQIIJ½GMIRX The work being done on malaria is important and interesting and the practical nature of lab work makes the days go by very quickly – a sure sign I was enjoying myself! Most importantly, I felt like I contributed something meaningful even in my short time at the Institute, which is more than I could have wished for prior to my placement.“ MRC National Institute for Medical Research 19 CAREERS Postdoctoral scientists -REHHMXMSRXSMXWVSPIMRXLIXVEMRMRKSJ4L(WXYHIRXW2-16MWEQENSVGIRXVIJSVJYVXLIVVIWIEVGLXVEMRMRKERHGEVIIV HIZIPSTQIRX-XEXXVEGXWVIWIEVGLIVWJVSQXLI9/ERHEGVSWWXLI[SVPHHYIXSXLIFVIEHXLERHUYEPMX]SJXLIVIWIEVGLERHXLI IQTLEWMWSRMRXIVEGXMSRWERHGVSWWHMWGMTPMREV]GSPPEFSVEXMSRW6IWIEVGLIVWEXEPPWXEKIWSJXLIMVGEVIIVFIRI½XJVSQXLIZIV]EGXMZI TVSKVEQQISJWIQMREVWERHMRXIVREPVIWIEVGLQIIXMRKWERHXLIEZEMPEFMPMX]SJGSYVWIWXSEGUYMVIOI]WGMIRXM½GERHGSQTPIQIRXEV] QEREKIVMEPWOMPPW 2-16LSWXWETTVS\MQEXIP]TSWXHSGXSVEPVIWIEVGLIVWWYTTSVXIHIMXLIVF]16'GSVIJYRHMRKSVI\XIVREPP]JYRHIHJIPPS[WLMTW 8LIGSVIJYRHMRKTVSQSXIWGEVIIVWEXXLITSWXHSGXSVEPPIZIPXLVSYKLXLVII]IEVTSWMXMSRW-REHHMXMSRXSXLIXVEMRMRKERHWYTTSVX SJJIVIHXSTSWXHSGXSVEPVIWIEVGLIVWF]2-16XLI4SWXHSG'SQQMXXIIMWZIV]EGXMZIEVVERKMRKWIQMREVWVIXVIEXWERHGEVIIVW WIWWMSRWEW[IPPEWWIZIVEPWSGMEPIZIRXWXLVSYKLSYXXLI]IEV-R8LI7GMIRXMWXVEROIH2-16XLMVHMRXLI9/EQSRK±&IWX 4PEGIWXS;SVOJSV4SWXHSGW² 2-16EPWSLEWEZMXEPVSPIMRTVSZMHMRKVIWIEVGLXVEMRMRKJSVGPMRMGEPWGMIRXMWXWERHXLMWMWERMQTSVXERXJEGMPMXEXSVSJXVERWPEXMSREP TVSNIGXWERHREXMSREPERHMRXIVREXMSREPGSPPEFSVEXMSRW2-16LSWXWQER]ZMWMXMRKTSWXHSGXSVEPGPMRMGEPWGMIRXMWXWJVSQXLI9/ERH EFVSEHGEVV]MRKSYXVIWIEVGLSRJSVI\EQTPIMRJIGXMSYWHMWIEWIWERHKIRIXMGHMWSVHIVW The Postdoc Committee 8LI4SWXHSG'SQQMXXIIMWGSQTSWIHSJTSWXHSGW[SVOMRKEX2-16MRHMJJIVIRX½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½VWXXMQIPEWX]IEVEX/MRK´W'SPPIKI0SRHSR[MXLXLIEMQSJIRGSYVEKMRK RIX[SVOMRKERHGSPPEFSVEXMSRFIX[IIRTSWXHSGWEXFSXLMRWXMXYXIW-RXLIGSQMRK]IEVXLI'SQQMXXIIEMQWXSGSRXMRYI[MXL GYVVIRXEGXMZMXMIWERHMRGVIEWIGSQQYRMGEXMSRWFIX[IIRTSWXHSGWEX2-16ERHXLSWIEXMRWXMXYXMSRWXLEX[MPPEPWSQSZIMRXSXLI 'VMGO The 2012 Postdoc committee: Robert Blassberg, Alexander Langley, Patricia Garcez, David Schwefel, Rohini Rana, Gerald Larrouy-Maumus 20 MRC National Institute for Medical Research CAREERS Postdoctoral scientists – in their own words Gerald Larrouy-Maumus, (MZMWMSRSJ1]GSFEGXIVMEP6IWIEVGL “My background lies in structural biochemistry. Since November 2011, the aim of my postdoctoral research in Luiz de Carvalho’s group consists of identifying new enzymes and unexpected metabolic pathways that can serve as new drug targets against the M. tuberculosis bacilli, the aetiologic agent of tuberculosis. This work is based on the use of high-resolution liquid chromatography-mass spectrometry. In this context, I believe NIMR is the place to be to work on such challenging project, as there is a considerable amount of expertise and a large variety of facilities available in the Institute. Due to the Institute’s commitment to excellence and the motivating working atmosphere, I see NIMR as a bridge to a future position as a group leader in another institute or university or equivalent position in industry or biotech. Moreover, at NIMR, postdoctoral fellows have close interactions both within and outside of the Institute. This is encouraged and facilitated by the postdoc committee. We expect similar and more exciting interactions and collaborations at the future Francis Crick Institute. Altogether these characteristics QEOI2-16ERMHIEPTPEGIJSVWGMIRXM½GJYP½PQIRXJSVETSWXHSGXSVEPJIPPS[² Patricia Garcez,(MZMWMSRSJ1SPIGYPEV2IYVSFMSPSK] “After completing a Biology degree in Brazil followed by a sandwich Ph.D. in Germany, I joined NIMR for a postdoctoral training position in Francois Guillemot’s group. My motivation to join NIMR was the possibility to learn new molecular neurobiology WOMPPWWTIGM½GEPP][MXLXLMWI\GIPPIRXVIWIEVGLKVSYT8LIWYVTVMWI[EWXLEXRSXSRP] is Guillemot’s group very committed to excellence but also the whole Institute has great support facilities and services. Our work focuses on understanding the role of a proneural factor in cell proliferation and also neuronal differentiation during brain development. Being a postdoc at NIMR is a great opportunity for my career. What I like best about working here is the people and also the generosity of colleagues, sharing their knowledge, always helping when there are experimental problems, or new protocols and reagents is needed. It is an honour to collaborate and learn with NIMR professionals. The interaction with the competent staff is in my opinion what makes XLMWTPEGIERHQ]S[RI\TIVMIRGILIVIGSQTPIXIERHYRMUYI² MRC National Institute for Medical Research 21 CAREERS Programme Leaders 1SWX4VSKVEQQI0IEHIVWEX2-16EVIMRMXMEPP]VIGVYMXIHSR4VSKVEQQI0IEHIV8VEGOTSWMXMSRW8LMWTVSZMHIWGSVIWYTTSVX JSVE½ZI]IEVTIVMSH[LMGLJSPPS[MRKI\XIVREPVIZMI[GERPIEHXSTVSQSXMSRXSERSTIRIRHIH16'4VSKVEQQI0IEHIV ETTSMRXQIRX8LMWPEXXIVTSWMXMSRTVSZMHIWPSRKXIVQGSVIWYTTSVXWYFNIGXXSVIKYPEVWGMIRXM½GVIZMI[XLEXIREFPIWEQFMXMSYW VIWIEVGLXSFIGEVVMIHSYX%RYQFIVSJWGMIRXMWXW[LSLEZIIWXEFPMWLIHXLIMVVITYXEXMSREX2-16LEZIKSRISRXSLIEHMRWXMXYXIW SVYRMZIVWMX]HITEVXQIRXWEVSYRHXLI[SVPH Luiz Pedro de Carvalho, (MZMWMSRSJ1]GSFEGXIVMEP6IWIEVGLNSMRIH2-16MR “I obtained my PhD from Albert Einstein College of Medicine in 2006, working on enzymology and inhibition studies. After that I spent nearly 5 years at Weill Cornell Medical College learning mycobacteriology, antibacterial drug discovery and metabolomics. The QEMRVIEWSR-PSSOIHEX2-16EWXLITPEGIXSWXEVXQ]VIWIEVGLKVSYT[EWWGMIRXM½G excellence. One of the professors at my old department in Cornell called me and asked if I was willing to apply for a position abroad. I replied “yes, depending on the place SJGSYVWI²3RGIWLIXSPHQIXLEXMX[EW2-16ERHEXXLI(MZMWMSRSJ1]GSFEGXIVMEP Research headed by Douglas Young, I got very excited and started working on the application immediately. I knew that NIMR had very strong programmes on areas such as structural biology and infectious diseases, which could synergize with the biochemistry and metabolomics I was planning on pursuing. I was familiar with the work of several group PIEHIVWERH-XLSYKLX-GSYPH½XMR[IPP Coming here to establish my group has been a fabulous experience. People are very JVMIRHP]ERHGSQQMXXIHXSLIPTIEGLSXLIV7YTTSVXMWEP[E]WEZEMPEFPI[LIRRIIHIHERHEKEMRWGMIRXM½GI\GIPPIRGIMWXLIGIRXVEP SFNIGXMZI-EQZIV]JSVXYREXIXSFIEFPIXSWXEVXQ]MRHITIRHIRXGEVIIVEXETPEGIWYGLEW2-16² Mike Gilchrist, (MZMWMSRSJ7]WXIQW&MSPSK]¯NSMRIH2-16MR ±1]WGMIRXM½GGEVIIVWXEVXIH[MXLE4L(MR1EXIVMEPW7GMIRGIEX'EQFVMHKIFYX hydrometallurgical electrochemistry was not for me. I took some time out to re-calibrate and began to travel with my cameras, exploring my interest in landscape imagery and visual art. )\LMFMXMSRWJSPPS[IHWSQITMGXYVIWWSPH-[EWFVMI¾]EREVXMWXMRVIWMHIRGI©&YXWGMIRGI[EW to reel me back in. Chance encounters brought molecular biologists into my circle of friends, and their willingness to talk about their work laid the foundations for Plan B – biology looked interesting. How could I get into it? So 1992 - I thought about doing another PhD, but sensed that computing would soon become a vital part of biology. Evening classes taught me programming languages, and a PYGO]FVIEOKSXQIENSFMRXLI½RERGIMRHYWXV]8[SFMSXIGLRSPSK]WXEVXYTWWLMJXIHXLIJSGYW ERH½REPP]VYRRMRKGSVIFMSMRJSVQEXMGWEXXLI+YVHSR-RWXMXYXIMR'EQFVMHKIGSQTPIXIHXLI transformation into something resembling a computational biologist. The decision to take the Systems Biology position I was offered at NIMR was easy – an STTSVXYRMX]XSWIIMJQ]S[RMHIEW[MPP¾]ERHLSTIJYPP]GSRXVMFYXIXSXLMWMRGVIEWMRKP] complex science. Being at NIMR has comfortably exceeded my expectations. The support from MRC is fantastic. The collaborative environment in the Institute brings new ideas into the frame all the time; and for me personally, there has been unexpected encouragement to take SRXLIGLEPPIRKISJI\TIVMQIRXEP[SVO8LMWLEWEHHIHE[LSPIRI[VERKISJTSWWMFMPMXMIW² 22 MRC National Institute for Medical Research CAREERS Gitta Stockinger, (MZMWMSRSJ1SPIGYPEV-QQYRSPSK] NSMRIH2-16MR “I came to NIMR after a 6-year period at the Basel Institute for Immunology, widely considered as a haven for immunological research. The unusual features at this place were the complete absence of hierarchy and a degree of independence for young researchers that was unparalleled elsewhere on the continent. Thus, when looking for a follow-on position I was acutely aware that I did not want to hand back my independence and integrate into a hierarchical system towards the bottom of the career ladder. -EP[E]WEHQMVIHXLI[E]WGMIRGI[EWGSRHYGXIHMRXLI9/-HMHQ]½VWX postdoc in the UK) and therefore when contacted by Dimitris Kioussis about the possibility to join a new Division of Molecular Immunology I did not hesitate. I have had a wonderful 21 years at NIMR since, where my science developed YRHIVXLIMR¾YIRGISJXLIVIWIEVGLIRZMVSRQIRX½VWXMRGSVTSVEXMRKQSPIGYPEV biology approaches through interaction with Dimitris Kioussis, Rose Zamoyska and Andy Mellor, my colleagues in the new Division. The fantastic animal facilities at NIMR and the support by Biological Services were another factor that promoted my research and I am E[EVIXLEXXLIOMRHSJQSYWIQSHIPW[I[IVIEFPIXSHIZIPSTLIVI[SYPHFIHMJ½GYPXXSWYWXEMREXER]SXLIVMRWXMXYXMSR[MXLMRXLI9/ Last but not least it is the open, collegial and interactive spirit at NIMR that continuously challenged and shaped my research questions ERHETTVSEGLIW² James Turner, (MZMWMSRSJ7XIQ'IPP&MSPSK]ERH(IZIPSTQIRXEP+IRIXMGWNSMRIH2-16WXEJJMR?4L(WXYHIRXA ±-½VWXLIEVHEFSYX2-16EWERYRHIVKVEHYEXIMRXIVIWXIHMRMRXIVGEPEXMRKE PhD into my medical degree. I was encouraged to apply, but was warned that because the standard of science and the expectations were very high, it would FIEFETXMWQSJ½VI-XGIVXEMRP][EW-EGGITXIHETSWMXMSRMR4EYP&YVKS]RI´W lab, which was carrying out paradigm-shifting work on sex chromosomes, but the genetics involved were complex and the intellectual leap was huge. During that period, it became clear to me that NIMR was unique. Here was a place where not just one, but every Division housed internationally renowned scientists, and where fundamental questions in science and medicine were tackled with unconventional, inspired approaches. Having completed my UCL medical degree, I returned to NIMR as a postdoc, spending a short period at Mount Sinai School of Medicine and the Whitehead Institute in the USA. My time away taught me a great deal, but what struck me was how similar the science experience in the USA is to that at NIMR. In 2007, I was promoted to a Programme Leader Track position and in 2012 was awarded tenure. For me, the secret to NIMR’s success is the fearless approach used XSXEGOPIWGMIRXM½GTVSFPIQWERHXLIYRYWYEPPIZIPSJMRXIKVEXMSRFIX[IIRWGMIRXM½GERHWYTTSVXWXEJJ[LMGLEGGIPIVEXIWWGMIRXM½GTVSKVIWW IRSVQSYWP]² MRC National Institute for Medical Research 23 CAREERS Research support 2-16SJJIVWGEVIIVSTTSVXYRMXMIWXLEXGERFIFVSEHP]XIVQIHVIWIEVGLWYTTSVXGSZIVMRKQER]HMJJIVIRXX]TIWSJNSFW6IWIEVGL 8IGLRMGMERWEVIPSGEXIH[MXLMRWTIGM½GTVSKVEQQIWERHEVIHMVIGXP]MRZSPZIHMRVIWIEVGL0EFSVEXSV]1EREKIVWPSSOEJXIVEPP XLIPEFWERHIUYMTQIRXSJSRISVQSVI(MZMWMSRWIRWYVMRKXLEXXLIWGMIRGIVYRWWQSSXLP]1ER]MRHMZMHYEPWEVIMRZSPZIHMRXLI VYRRMRKSJ2-16´WI\XIRWMZIJEGMPMXMIW8LIFMKKIWXSJXLIWI&MSPSKMGEP7IVZMGIWTVSZMHIWEJYPP]MRXIKVEXIHPEFSVEXSV]ERMQEPERH XIGLRMGEPVIWSYVGIXSXLI-RWXMXYXI*MREPP]XLI-RWXMXYXIIQTPS]WMRHMZMHYEPWMREVERKISJRSRWGMIRXM½GEGXMZMXMIWMRGPYHMRK(MZMWMSREP %HQMRMWXVEXSVW4IVWSREP%WWMWXERXW,YQER6IWSYVGIW%GGSYRXW4VSGYVIQIRX7XSVIWERH7IGYVMX] Rachel Chung, 0EFSVEXSV]1EREKIV ±*SV]IEVW-LEZIFIIREPEFVIWIEVGLXIGLRMGMER1]½VWXNSF[EWEXXLI&MS Products Laboratory in Elstree as a Research Assistant, working with blood products like plasma, IgG and Factor VIII. My role in the R&D department was to help develop RI[HMEKRSWXMGWERHMQTVSZITVSHYGXMSRQIXLSHW%JXIV½ZI]IEVW-XSSOYTETEVX XMQITSWMXMSREX7X8LSQEW´,SWTMXEPEJXIVQ]½VWXHEYKLXIV[EWFSVR;LIRQ] second daughter was born I decided to go back to full-time work and joined NIMR. %X½VWX-[SVOIHMRX[SHMJJIVIRXPEFWMRXLI(MZMWMSRSJ:MVSPSK][SVOMRK[MXL,-:ERH HPV and later moved to Developmental Neurobiology. In July 2012 I successfully applied for a Lab Manager position, seeing this as my best chance for career progression. %WE0EF1EREKIV-TVSZMHITVMQEVMP]XIGLRMGEPERH½RERGMEPQEREKIQIRXWYTTSVX Lab Managers at NIMR are ‘jacks of all trades’ who are ready to deal with dayto-day issues – anything that affects the research of our scientists, from resolving a blocked sink to making sure an important payment was completed. The work is IRHPIWWFYXZEVMIHGLEPPIRKMRKERHVI[EVHMRK-IRNS]XLI¾I\MFMPMX]-LEZIMRWIXXMRKQ] own schedules, and the busy nature of the role: there are rarely any boring moments. I also act as safety and radiation advisor to the Divisions I serve and advise on safety in containment labs. Above all, I enjoy the interaction with people who help to resolve our HEMP]TVSFPIQWXLI]EVILIPTJYPERHIJ½GMIRXERHEJXIVEPPXLIWI]IEVW2-16MWWXMPP XLIJVMIRHPMIWXTPEGI-LEZIIZIV[SVOIH² Sim Tung, 6IWIEVGL8IGLRMGMER(MZMWMSRSJ-QQYRI'IPP&MSPSK] “After graduating from university, I started working as a Lab Demonstrator. I enjoyed XLMWWGMIRXM½GXIEGLMRKVSPIFYXMXPEGOIHXLILERHWSRI\TIVMQIRXEP[SVO-WXVMZIHJSV- applied to work at NIMR since they have a reputation for excellent research facilities and a highly collaborative environment. Indeed there is a very positive attitude to GSPPEFSVEXMSRWEGVSWW(MZMWMSRW-XMWIEW]XS½RHEOMRHGSPPIEKYIXSWLS[]SYLS[XSYWI equipment and to share their protocols and knowledge. My role is as a Research Technician in Immune Cell Biology where I have worked for the past four and a half years. My job mainly involves the genotyping and maintenance of breeding mouse lines, ensuring the smooth running of the lab on a daily basis and providing technical assistance for colleagues’ experimental work. Through the years, I have acquired a diverse range of research techniques. The job is overall very varied with opportunities to carry out your own research projects and make contributions to TYFPMGEXMSRW-XMWSJXIRGLEPPIRKMRKFYXZIV]VI[EVHMRKERHIRNS]EFPI² 24 MRC National Institute for Medical Research CAREERS Abdul Karim Sesay, +IRSQMGW*EGMPMX]1EREKIV “My laboratory career started when I did my industrial placement as part of a sandwich undergraduate degree at the Middlesex Hospital Medical School in Central London (now part of University College Hospital). I went back to the same lab to work and do a PhD as a part-time student. In 1991 I came to NIMR to work as a postdoc in Tony Lai’s lab in the Division of Physical Biochemistry. The lab then moved into the division of Neurophysiology and Neuropharmacology (NN). Following Tony’s departure I became part of Tim Bliss’s group in 1996. I worked with Tim until he retired in 2009. -GSQTPIXIHE&MSMRJSVQEXMGW1EWXIVWHIKVIIHYVMRKQ]½REP]IEVMR22- was asked by the present Director to establish and run the new core Genomics *EGMPMX]-LEZIFIIRI\XVIQIP]PYGO][MXLQ]WGMIRXM½GPMJIMRXLI-RWXMXYXI I have had great supervisors who have been supportive of my career and have given me the opportunities to professionally develop myself and learn new skills. All this has led directly to my present position, which has been like walking into my dream job without having to leave home and the family unit of NIMR. I have also been involved in the social aspect of NIMR by playing an active part in NIMROD, our staff EWWSGMEXMSRMRQSWXSJQ]XMQILIVI2-16LEWFIIREKVIEXERHWYGGIWWJYPTEVXSJQ]WGMIRXM½GPMJIERH-EQKVEXIJYPXSQ]TEWXERH TVIWIRXWYTIVZMWSVWERHGSPPIEKYIW² Anna Gibson, 4VSGYVIQIRX1EREKIV “Surprisingly, as a child I did not dream about working in Finance and Procurement, I wanted to be an astronaut. Later in life, studying neuroscience and during my PhD in Developmental Neurobiology at UCL, I only envisaged EWGMIRXM½GGEVIIV-LEHEWLSVXTSWXHSGTSWMXMSRXLIREWLSVXWTIPPEWE0EF Manager, and I decided that I valued the security of a career in research support more than the academic freedom of original research. I joined NIMR over four years ago as a Laboratory Manager. There is something very special about NIMR, the wonderful community we comprise, a place where people matter, friendships are built and most importantly great science happens. I feel proud that I can still contribute to science, even in an indirect way. NIMR has allowed me to realise my strengths, to believe in myself and to build a career. Recently, I moved into Procurement where I am responsible for capital equipment purchases, the asset database, and service and maintenance contracts. In addition, I am involved in the preparation for transition to the Crick. Thanks to NIMR, I am in the process of obtaining a diploma in Purchasing and Supply and am hoping to be EGXMZIP]MRZSPZIHMRWLETMRKSYVJYXYVIEXXLI'VMGOERHIRWYVMRKXLEXWGMIRXMWXWGERGSRGIRXVEXISRWGMIRGIERHVIWIEVGL² MRC National Institute for Medical Research 25 CAREERS Animal Technicians 2-16MWGSQQMXXIHXSIRWYVMRKELMKLWXERHEVHSJXVEMRMRKERHIHYGEXMSRJSV%RMQEP8IGLRMGMERWERHWYTTSVXWXEJJEXEPPWXEKIWSJ XLIMVGEVIIVW'SRXMRYSYW4VSJIWWMSREP(IZIPSTQIRX'4(JSV%RMQEP8IGLRMGMERWEX2-16MRGPYHIWJSVQEPERHMRJSVQEPPIEVRMRK XVEMRMRKERHI\TIVMIRGIW'SQTIXIRG]FEWIHUYEPM½GEXMSRWEPPS[XVEMRMRKWTIGM½GXSXLIMRHMZMHYEPERHXLIMV[SVO[LMPI3TIR 9RMZIVWMX]ERH-RWXMXYXISJ%RMQEP8IGLRSPSK]UYEPM½GEXMSRWHIPMZIVE[MHIORS[PIHKISJPEFSVEXSV]ERMQEPWGMIRGIXLI6WERHE KSSHFEGOKVSYRHMRFMSPSKMGEPWGMIRGIW8IGLRMGMERWEVIIRGSYVEKIHXSWTIRHXMQIMR2-16VIWIEVGLPEFWMRSVHIVXSKEMRLERHW SRI\TIVMIRGISJI\TIVMQIRXEPTVSGIHYVIWERHEXXIRH[SVOWLSTWERHWIQMREVWLIPHSREVIKYPEVFEWMWSRWYFNIGXWVIPEXIHXS PEFSVEXSV]ERMQEPWGMIRGI:MWMXWXSSXLIVWGMIRXM½GIWXEFPMWLQIRXWW]QTSWMEERHMRXIVREXMSREPQIIXMRKWEVIEPWSSVKERMWIH[LMGL IREFPIXIGLRMGMERWXSKEMRI\TIVMIRGIMRQSVIZEVMIHEWTIGXWSJPEFSVEXSV]ERMQEPLYWFERHV]ERHWGMIRGIIRWYVMRKXLI6WEVI IQFIHHIHMREPP[SVOMRZSPZMRKERMQEPWEXXLI-RWXMXYXI Gabriel Wills, %RMQEP8IGLRMGMER “I initially joined NIMR as a support team member in 2010. My training started from the very beginning in different areas such as sterilisation, maintaining FEVVMIVWERHQSVIKIRIVEPP]LS[XSHIPMZIVE½VWXGPEWWWIVZMGIXSWYTTSVXXLI science. Since then I started to attend different workshops and seminars that are held on a regular basis. Moreover, I decided to look beyond this job and explore work related to animal care. I had the opportunity to visit different animal units and gained some knowledge about animal care, animal handling and general animal husbandry. By the beginning of 2012 I had decided I wanted to become an animal technician, and was promoted to this job by the end of 2012. With this promotion I had the opportunity to complete the CPD (Continuous Professional Development) Level 2 in Animal Technology. Taking this course has been very YWIJYPFIGEYWIMXLIPTIHQIXSVI½RIXLIORS[PIHKI-LEHTVIZMSYWP]KEMRIHERHEPWSXSYRHIVWXERHMRHIXEMPXLIPIKEPERHIXLMGEP EWTIGXWSJERMQEP[IPJEVIERHERMQEPVIWIEVGL;MXLSYXHSYFXXLI'4(0IZIPGSYVWILEWKMZIRQIXLIGSR½HIRGIERHWOMPPWRIIHIHXS GEVV]SYXQ]HYXMIWXSELMKLWXERHEVH² Joanna Butt, 7IRMSV%RMQEP8IGLRMGMER “I joined NIMR 21 years ago as a Junior Animal Technician. After in-house training I attended a day-release course and gained the IAT Animal Technology 'IVXM½GEXI7MRGIXLIR-LEZIEXXIRHIHWIZIVEPWIQMREVWERHGSYVWIWXSIRLERGI my knowledge not only of my job but also the science based at the Institute. After becoming a Senior Technician in 2009 I completed the NVQ Level 3 in Animal Technology. This both enhanced my knowledge and taught me more about other units and species used within NIMR. For this course I had to go out and research the topics myself, giving me more contact with other staff around the Institute. Some of my main duties are animal husbandry and welfare, overseeing colony management, co-ordinating staff within the unit, corresponding with scientists about their orders and delivering the service and support required for their research, aiding in the general running of the unit/ordering supplies. I also train WXEJJERHIRWYVIXLEXQ]XIEQQIQFIVWLEZIXLIWOMPPWRIGIWWEV]XSSJJIVE½VWXGPEWWWIVZMGI-RXLIIZIVGLERKMRK[SVPHSJWGMIRGIXLIVI is always a need to adapt and change techniques in both husbandry and procedures, so staff are encouraged to expand their knowledge, KEMRRI[WOMPPWERHEMQJSVXLILMKLIWXWXERHEVHSJERMQEPLYWFERHV]ERH[IPJEVI² 26 MRC National Institute for Medical Research TRANSLATIONAL RESEARCH Support for translation Eileen Clark 0EFSVEXSV]FEWIHWXYHMIWEX2-16YRHIVTMRXLI16'´W QMWWMSRXSMQTVSZILYQERLIEPXLXLVSYKLVIWIEVGL (MWGSZIVMIWSJLS[QSPIGYPIWGIPPWERHSVKERWEVIJSVQIH VIKYPEXIHERHJYRGXMSRTVSZMHIXLIORS[PIHKIXLEXGERPIEH XSRI[XLIVETMIWERHHMEKRSWXMGW8LMW³MRXIPPIGXYEPTVSTIVX]´ ERHMXWXVERWPEXMSRMRXSTVSHYGXWWYGLEWYWIJYPRSZIPHVYKW SVZEGGMRIWJIIHWMRXSGSQQIVGMEPTVSNIGXWXLEXGERFYMPH SRXLMW³ORS[LS[´ERH8IGLRSPSK]8VERWJIVJEGMPMXEXIWXLMW I\TPSMXEXMSR 7SQIWXYHMIWEVIGPSWIP]EPMKRIHXSWTIGM½GLYQERHMWIEWIW ERHXLMWVIWIEVGLFIRI½XWJVSQGPSWIMRXIVEGXMSRW[MXL GPMRMGMERW4VSHYGXMZII\GLERKIFIX[IIRFEWMGWGMIRXMWXWERH GPMRMGMERWEPPS[WQSHIPW]WXIQWXSFIYWIHXSXLIMVKVIEXIWX EHZERXEKIMRWGMIRXM½GHMWGSZIV]ERHTVSZMHIWMRWMKLXW MRXSXLIHMWIEWITVSGIWWMRTEXMIRXWEW[IPPEWTSXIRXMEP XVIEXQIRXWERHMQTVSZIHGPMRMGEPGEVI Technology Transfer 2-16WGMIRXMWXWEVIWYTTSVXIHF]EPSGEP8IGLRSPSK]8VERWJIV3J½GI[LMGLTVSZMHIWQIGLERMWQWERHWXVYGXYVIXSEPPS[FEWMG XIGLRSPSK]XVERWJIVEGXMZMXMIWWYGLEWQEXIVMEPXVERWJIVEKVIIQIRXWGSPPEFSVEXMSREKVIIQIRXWERHGSR½HIRXMEPMX]EKVIIQIRXWXSFI HIEPX[MXLPSGEPP]ERHWTIIHMP]8LI3J½GIMWEPWSVIWTSRWMFPIJSVVEMWMRKE[EVIRIWWSJMRXIPPIGXYEPTVSTIVX]MWWYIWERHIRGSYVEKMRK WGMIRXMWXWXSFIEPIVXXSTSXIRXMEPI\TPSMXEXMSRSTTSVXYRMXMIW 16'8IGLRSPSK]16'8MWXLII\GPYWMZIXIGLRSPSK]XVERWJIVEKIRXJSVXLI1IHMGEP 6IWIEVGL'SYRGMPERHMWVIWTSRWMFPIJSVXVERWPEXMRKGYXXMRKIHKIWGMIRXM½GHMWGSZIVMIW MRXSGSQQIVGMEPTVSHYGXW-REHHMXMSRXLI]LEZIWQEPPQSPIGYPIHVYKHMWGSZIV]ERH XLIVETIYXMGERXMFSH]JEGMPMXMIWTVSZMHMRKPIEHWXEKIXLIVETIYXMGEWWIXWXSTLEVQEGIYXMGEP ERHFMSXIGLRSPSK]GSQTERMIW16'8IGLRSPSK]EHHWZEPYIXSGYXXMRKIHKIWGMIRXM½G HMWGSZIVMIWXLVSYKLWXVEXIKMGTEXIRXTVSXIGXMSRERHGVIEXMZIPMGIRWMRKSJMRXIPPIGXYEP TVSTIVX]-4SVXLVSYKLTEVXRIVIHVIWIEVGL[MXLMRHYWXV])\EQTPIWSJPMGIRWIH XIGLRSPSK]MRGPYHIXVERWKIRMGQMGIERHGV]WXEPWXVYGXYVIW2-16WGMIRXMWXWLEZIEZEVMIX] SJMRHYWXVMEPGSPPEFSVEXMSRWERHEPWSEGXEWGSRWYPXERXWXSEVERKISJGSQTERMIW %XVERWPEXMSRGPYFJSV2-16WGMIRXMWXWTVSQSXIWGSPPEFSVEXMSRWRIX[SVOW[MXL16'8XLITLEVQEGIYXMGEPMRHYWXV]GPMRMGMER WGMIRXMWXWERHIRKMRIIVW-XEMQWXSEGLMIZIFIXXIVXVERWPEXMSREPI\TPSMXEXMSRSJ2-16WGMIRXMWXW´½RHMRKWVIEKIRXWQIXLSHSPSKMIW ERHIUYMTQIRX-XQIIXWX[SSVXLVIIXMQIWE]IEVERHMREHHMXMSRXS2-16WGMIRXMWXWMRZSPZIWVITVIWIRXEXMZIWJVSQOI]TEVXRIVW MRGPYHMRK16'8ERH9RMZIVWMX]'SPPIKI0SRHSR,SWTMXEPXSHMWGYWWRI[STTSVXYRMXMIWJSVXVERWPEXMSRERHXSVEMWIXLISZIVEPP E[EVIRIWWSJTSXIRXMEPMRXIVIWXMRKSTTSVXYRMXMIW-REHHMXMSRXLIGPYFEMQWXSFVMRKMREGVSWWWIGXMSRSJI\TIVXWJVSQTSXIRXMEP TEVXRIVWEWKYIWXWTIEOIVWSRERad hocFEWMWXSSTIRYTRI[MHIEWERH[E]WSJXLMROMRK'EWIWXYHMIWSJTVIZMSYW2-16 WYGGIWWIWMRXVERWPEXMSRLEZIFIIRTVIWIRXIHXS4VSKVEQQI0IEHIVWEXXLI-RWXMXYXI8LIGPYFEMQWXSIWXEFPMWLERMRJSVQEP RIX[SVOSJGSRXEGXWXLEXMWVIEHMP]EGGIWWMFPIXS2-16WGMIRXMWXWMRSVHIVXSLIPTI\TPSMXXLIMV½RHMRKW MRC National Institute for Medical Research 27 TRANSLATIONAL RESEARCH Commercial translation Phosphate biosensor %FEWMGVIWIEVGLTVSKVEQQISRQSXMPMX]TVSXIMRWVIUYMVIH EVETMHERHWIRWMXMZI[E]XSQIEWYVIMRSVKERMGTLSWTLEXI SRITVSHYGXSJ%84L]HVSP]WMW8LMWPIHXSERSZIPETTVSEGL E¾YSVIWGIRXVIEKIRXPIWWFMSWIRWSV8LIGSRGITXMW WXVEMKLXJSV[EVH%TVSXIMRMWYWIHEWXLIFMSWIRWSVJVEQI[SVO XSMRXIVEGX[MXLXLIXEVKIXQSPIGYPIMRXLMWGEWITLSWTLEXI ERHMWQSHM½IHF]EXXEGLQIRXSJE¾YSVIWGIRXVITSVXIV &MRHMRKSJPMKERHWSJXIRVIWYPXWMRVETMHGSRJSVQEXMSREP GLERKIWERHXLIWIGERFIVIEHSYXF]GLERKIWMRXLI ¾YSVIWGIRXVITSVXIV%TLSWTLEXIFMRHMRKTVSXIMR[EWGLSWIR ERHE¾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¾YSVSTLSVIMR red, inorganic phosphate in blue). (Martin Webb) Mouse House 2-16%RMQEP8IGLRMGMERWPIHXLI[SVOXSHIZIPSTETVSZIR IRVMGLQIRXHIZMGIXLEXLEWWMKRM½GERXP]IRLERGIHXLI[IPJEVI SJPEFSVEXSV]QMGIXLI1SYWI,SYWI[LMGL[EWTEXIRXIH F]XLI16'ERHMWRS[QEVOIXIHF]8IGLRMTPEWX9/3ZIV 1SYWI,SYWIWLEZIFIIRWSPH[SVPH[MHI8LI XVERWTEVIRXVIHMWSJEWTIGM½G[EZIPIRKXLXLEXXLIQMGIWII EWHEVOKVI]8LYW[LIRMRWMHIXLI1SYWI,SYWIQMGIJIIP WIGYVI[LMPI8IGLRMGMERWGERWXMPPWIIMRXSGEVV]SYXVSYXMRI GLIGOWERHLYWFERHV]7XYHMIWLEZIWLS[RXLEXXLIQSYWI LSYWILIPTWXSVIHYGIEKKVIWWMSRERHMQTVSZIWFVIIHMRK TIVJSVQERGI[LMGLMWIWTIGMEPP]MQTSVXERXMRXVERWKIRMG QSYWIWXVEMRW8LIHIWMKRIVWSJXLI1SYWI,SYWI[IVI E[EVHIHXLI³%RMQEP;IPJEVI%[EVH´F]XLI7[MWW 7SGMIX]JSV0EFSVEXSV]%RMQEP7GMIRGIXLI½VWXRSREGEHIQMG VIGMTMIRXWSJXLMWTVIWXMKMSYWE[EVH The Mouse House. 28 MRC National Institute for Medical Research TRANSLATIONAL RESEARCH Clinical translation 4EXLSKIRWGSRXMRYIXSFPMKLXLYQERLIEPXLERHSYVVIWIEVGLSRMRJIGXMSYWHMWIEWIWWYGLEWMR¾YIR^EQEPEVMEERHXYFIVGYPSWMW 8&FIRI½XWJVSQERHMRJSVQWGPMRMGEPTVEGXMGI[SVPH[MHI0EFSVEXSV]VIWIEVGLERHERMQEPQSHIPWJSVLYQERHMWIEWIWTVSZMHI TVEGXMGEPMRWMKLXWXLEXGERXVERWPEXIMRXSGPMRMGEPFIRI½X -R¾YIR^E 8LI2-16;,3'SPPEFSVEXMRK'IRXVIJSV6IJIVIRGIERH6IWIEVGLSR-R¾YIR^EWIITEKIMWTEVXSJXLIKPSFEPWYVZIMPPERGI W]WXIQERHMWSRISJWM\GSPPEFSVEXMRKGIRXVIWXLEXEWWIWWXLIERXMKIRMGERHKIRIXMGGLEVEGXIVMWXMGWSJMR¾YIR^EZMVYWIWJVSQEVSYRH XLI[SVPH8LIWIGIRXVIWEHZMWIXLI;,3ERHJSVQYPEXIXLIX[MGI]IEVP]VIGSQQIRHEXMSRWJSVXLIGSQTSWMXMSRSJWIEWSREP MR¾YIR^EZEGGMRIW8LIGIRXVIWEPWSEHZMWIXLI;,3SRXLIIQIVKIRGISJHVYKVIWMWXERXZMVYWIWERHSRXLILYQERTERHIQMG TSXIRXMEPSJERMQEPMR¾YIR^EZMVYWIW Malaria 8LI'LMPHLSSH1EPEVME6IWIEVGL+VSYTMWETEVXRIVWLMTFIX[IIRXLI(MZMWMSR SJ4EVEWMXSPSK](IPQMVS*IVRERHI^6I]IWERH8SR],SPHIVERHXLI'SPPIKI SJ1IHMGMRI9RMZIVWMX]SJ-FEHER9RMZIVWMX]'SPPIKI,SWTMXEPMR-FEHER2MKIVME 8LMWGSPPEFSVEXMSRFVMRKWXSKIXLIVXLIQSPIGYPEVI\TIVXMWISJ2-16ERHXLI GPMRMGEPWOMPPWERHLSWTMXEPMRJVEWXVYGXYVIJSVXLIQEREKIQIRXSJWIZIVIQEPEVME MR-FEHER[LIVIQEPEVMEMWSRISJXLIQSWXGSQQSRGEYWIWSJHIEXLMR]SYRK GLMPHVIR6IWIEVGLSRXLIQSPIGYPEVFEWMWSJWIZIVIQEPEVMEFIRI½XWJVSQXLI GPSWIEPMKRQIRX[MXLGPMRMGEPWTIGMEPMWXWERHTVSZMHIWEPEFSVEXSV]VIWIEVGL GETEFMPMX]GPSWIXSTEXMIRXTSMRXSJGEVI&MSQEVOIVWXLEXTVIHMGXHMWIEWIWIZIVMX] LEZIFIIRHI½RIHERHLEZIXLITSXIRXMEPJSVHIZIPSTQIRXMRXSXSSPWJSVHMWIEWI TVSKRSWMWERHGPMRMGEPQEREKIQIRX6IGIRX[SVOSRLITGMHMRWYKKIWXWXLEXMVSR WYTTPIQIRXEXMSRQMKLXRSXFIRIGIWWEV]MRXLIQEREKIQIRXSJWIZIVIGLMPHLSSH QEPEVME Tuberculosis and HIV-TB coinfection Waiting at the Children’s Outpatient Clinic, University College Hospital, Ibadan, Nigeria. &EGXIVMEPVIWTMVEXSV]MRJIGXMSRWVIQEMREQENSVKPSFEPGEYWISJHIEXLHIWTMXIXLI EZEMPEFMPMX]SJERXMFMSXMGW0EXIRXXYFIVGYPSWMWMRJIGXMSREJJIGXWSRIXLMVHSJXLI[SVPH´WTSTYPEXMSRERH XLIVIEVIQMPPMSRRI[ EGXMZIXYFIVGYPSWMWGEWIWERHQMPPMSRHIEXLWERRYEPP]HYIXSTEXLSPSKMGEPMR¾EQQEXSV]VIWTSRWIW-RXLITVIERXMFMSXMGIVE ZMXEQMR([EWYWIHXSXVIEXXYFIVGYPSWMW:MXEQMR(MRHYGIWMRREXIERXMQMGVSFMEPVIWTSRWIWERHWYTTVIWWIWTVSMR¾EQQEXSV] cytokine responses in vitroFYXXLIIJJIGXWSJZMXEQMR(WYTTPIQIRXEXMSRSRMQQYRIVIWTSRWIWMRLYQERW[EWYRORS[R-REXVMEP JYRHIHF]XLI&VMXMWL0YRK*SYRHEXMSRERHEGSPPEFSVEXMSRFIX[IIREKVSYTSJ0SRHSRLSWTMXEPWERH6SFIVX;MPOMRWSR´WKVSYT XLIMR¾YIRGISJLMKLHSWIZMXEQMR(SRFEGXIVMEPGPIEVERGIMRTEXMIRXWVIGIMZMRKERXMFMSXMGXVIEXQIRXJSVTYPQSREV]XYFIVGYPSWMW [EWIZEPYEXIH-X[EWJSYRHXLEXLMKLHSWIZMXEQMR(KMZIR[MXLERXMFMSXMGXVIEXQIRXEGGIPIVEXIWXLIVIWSPYXMSRSJMR¾EQQEXSV] VIWTSRWIWERHLIPTWXLITEXMIRXWXSVIGSZIVQSVIUYMGOP]8LMWGERPIEHXSTEXMIRXWFIMRKMRJIGXMSYWJSVEWLSVXIVTIVMSHSJXMQI ERHWYJJIVMRKPIWWPYRKHEQEKI MRC National Institute for Medical Research 29 TRANSLATIONAL RESEARCH Clinical translation 'PSWIXMIWMR7SYXL%JVMGEXLI;MPOMRWSRKVSYTEXXLI9RMZIVWMX]SJ'ETI8S[RERH0SRHSRLEZIEPPS[IHEXIEQSJFEWMG VIWIEVGLIVWGPMRMGMERWERHFMSMRJSVQEXMGMERWPIHF]%RRI3´+EVVEXSMHIRXMJ]EXVERWGVMTXMSREPWMKREXYVIMRXLIFPSSHSJEGXMZI8& TEXMIRXWERHEFWIRXMRXLIQENSVMX]SJEW]QTXSQEXMGPEXIRXERHLIEPXL]MRHMZMHYEPW8LMWWMKREXYVISJEGXMZIXYFIVGYPSWMWGSVVIPEXIW [MXLXLII\XIRXSJPYRKHMWIEWIERHMWHMQMRMWLIHYTSRXVIEXQIRXXLYWSJJIVMRKTSXIRXMEPFMSQEVOIVWJSVHMEKRSWMWERHXVIEXQIRX QSRMXSVMRK)JJIGXMZIIEVP]XVIEXQIRXMWIWWIRXMEPXSTVIZIRX[SVWIRMRKHMWIEWIHMWIEWIXVERWQMWWMSRERHHVYKVIWMWXERGI-RE JSPPS[YTWXYH]SJEGXMZI8&WMKRM½GERXGLERKIWMRXVERWGVMTXMSREPTVS½PIW[IVIHIXIGXEFPIX[S[IIOWEJXIVXLIWXEVXSJXVIEXQIRX TVSZMHMRKWYVVSKEXIFMSQEVOIVWSJEWYGGIWWJYPXVIEXQIRXVIWTSRWI -REGSPPEFSVEXMSRFIX[IIR(IPQMVS*IVRERHI^6I]IWEX2-16ERHKVSYTWJVSQ-QTIVMEP'SPPIKIXLI97%ERH4IVYMX[EWWLS[R XLEXTEXMIRXW[MXLEGXMZI8&GEREPWSFIHMWXMRKYMWLIHJVSQXLSWI[MXLPEXIRXMRJIGXMSRERHJVSQRSR8&TEXMIRXW[MXLSZIVPETTMRK GPMRMGEPfeatures YWMRKTPEWQETVSXISQITVS½PMRK8LMWGSR½VQWXLEXTVSXISQMGTEXXIVRWGEREPWSFIYWIHEWEHMEKRSWXMGETTVSEGL XSMHIRXMJ]EGXMZI8& 8VERWPEXMSRSJFMSQEVOIVWMRXSEWYMXEFPITSMRXSJGEVIJSVQEX[MPPLEZIWMKRM½GERXMQTPMGEXMSRWJSVVIGSKRMXMSRERHGSRXVSPSJEGXMZI 8&MRLMKLTVIZEPIRGIWIXXMRKW A new animal model for Sudden Infant Death Syndrome 7YHHIR-RJERX(IEXL7]RHVSQI7-(7SV³GSXHIEXL´MWEWYFWXERXMEPQIHMGEPTVSFPIQ6EXIWSJEVSYRHSRIHIEXLMRIZIV] ETTEVIRXP]LIEPXL]MRJERXWQEOI7-(7XLIPIEHMRKGEYWISJHIEXLMRXLI½VWX]IEVSJPMJIEJXIVXLIRISREXEPTIVMSH8LITEXLSPSK] SJ7-(7XLIYRHIVP]MRKGEYWIWERHXLIQIGLERMWQSJHIEXLEVITSSVP]YRHIVWXSSH8LIQENSVMX]SJVMWOJEGXSVWJSV7-(7EVI EWWSGMEXIH[MXLPS[PIZIPWSJS\]KIRMRXLIRI[FSVRFYXXLIWMKRM½GERGISJXLMWMWGSRXVSZIVWMEP6SWW&VIGOIRVMHKIERH1EVMERRI 2IEV]MR8MQ1SLYR´WKVSYTLEZIHIZIPSTIHERI[QSYWIQSHIP[MXLEKIRIXMGEPP]EPXIVIHGIPPYPEVS\]KIRWIRWMRKW]WXIQ8LI GIPPWMRXLILIEVXWSJXLIWIQMGIJYRGXMSREWMJXLI]EVIMRPS[S\]KIRGSRHMXMSRWERHXLIWIQMGILEZIXLI)'+EFRSVQEPMXMIWXLEX EVIEWWSGMEXIH[MXLMRJERXWEXVMWOSJ7-(78LIVIWIEVGLIVWTVSTSWIEQSHIPXLEXPMROWRISREXEPL]TS\ME[MXLWYHHIRHIEXLF] GEVHMEGEVVL]XLQMEF]QMWVIKYPEXMSRSJGEVHMEG'\ERHMSRGLERRIPW8LIWXYH]WYKKIWXWJSVXLI½VWXXMQIXLEXXLIVIMWEHMVIGX IJJIGXSJS\]KIRPIZIPWSRXLIQ]SGEVHMYQSJMRJERXW8LMW[SVOWLSYPHEPPS[MRWMKLXWMRXSXLIQIGLERMWQSJ7-(7ERHJYVXLIV [SVOSRTVIZIRXEXMZIXVIEXQIRXW Mycobacterium tuberculosis (Mtb) in a macrophage. Green =Mtb; Blue = macrophage nucleus 30 MRC National Institute for Medical Research Analysis of the SIDS mouse model which is engineered to upregulate hypoxia signalling in the heart at normal levels of oxygen, PUBLIC OUTREACH Public engagement Human Biology Essay Competition 8LIERRYEP2-16,YQER&MSPSK])WWE]'SQTIXMXMSREMQWXSJSWXIVERMRXIVIWXMRGSQQYRMGEXMRKWGMIRXM½GMRJSVQEXMSRXSE KIRIVEPEYHMIRGIERHXSKMZIWGLSSPWXYHIRXWWSQITVEGXMGIMRIWWE][VMXMRK8LIXIRXL)WWE]'SQTIXMXMSR[EW[SRF](EZMRE7YM %RR'LESSJ7X4EYP´W+MVPW´7GLSSP[LS[VSXISR±%VI[IXSSGPIERJSVSYVS[RKSSH#²%PPXLIIRXVERXWVIGIMZIETVM^ISJXLI GYVVIRXZSPYQISJ1MPP,MPP)WWE]W[LMPIXLI[MRRIVERHX[SVYRRIVWYTVIGIMZIE½RERGMEPTVM^IERHWTIRHEHE]EX2-16WIIMRK ZMWYEPP]ETTIEPMRKTVSNIGXW Research Summer School -RWYQQIV2-16TPE]IHLSWXXSXIRWXYHIRXWHVE[RJVSQXIRPSGEPWGLSSPW8LI7YQQIV7GLSSPMW½RERGIHF]XLI2YJ½IPH *SYRHEXMSR[LMGLE[EVHWFYVWEVMIWXSIEGLWXYHIRX8LIWXYHIRXWYRHIVXEOITVSNIGXWHIZMWIHERHWYTIVZMWIHF]2-16WXEJJYWMRK XLIGSVIXIGLRMUYIWSJQSHIVRQSPIGYPEVFMSPSK]ERHFMSGLIQMWXV]8LIGSYVWIWXEVXW[MXLELEPJHE]MRHYGXMSRMRQSPIGYPEV FMSPSK]PEFWOMPPWWEJIX]ERHVIGSVHOIITMRK7XYHIRXWTVSHYGII\GIPPIRXTSWXIVWERHVITSVXWSJXLIMV[SVOXSFIWLS[REXIZIRXW SVKERMWIHF]XLI2YJ½IPH*SYRHEXMSR8IEGLIVWXIPPYWXLEXFYVWEV]LSPHIVWEVIEZMZMHEHZIVXMWIQIRXJSVXLI7YQQIV7GLSSPERH XLI]MRWTMVIXLIRI\XKIRIVEXMSRSJWGMIRGIWXYHIRXWXSJSPPS[XLIWEQIVSYXI7SQISJSYVIEVPMIVGSLSVXWSJWXYHIRXWEVIRS[ VIWIEVGLIVWLEZMRKIQIVKIHJVSQYRMZIVWMX][MXL½VWXGPEWWHIKVIIW Annual Schools Days 7XYHIRXWMR=IEVEVIMRZMXIHXSERIZIRXHIWMKRIHXSIRVMGLXLIMVI\TIVMIRGISJXLIPMJIWGMIRGIW8LIXLIQIJSVXLMW]IEV´WIZIRX [EW³&MKXSWQEPP´[MXLXEPOWSRIQFV]SPSK]GSRRIGXSQMGWERHLMKLXLVSYKLTYXWIUYIRGMRK7SVVIP&MGOPI]KEZIEPMZIP]EGGSYRXSJ XLIIQFV]SPSKMGEPSVMKMRWERHFMSPSKMGEPWMKRM½GERGISJXLIWXIVRYQMPPYQMREXIH[MXLPSXWSJREXYVEPLMWXSV]ERHMRXIVIWXMRKMRWMKLXW MRXSIZSPYXMSREV]FMSPSK])HI6ERG^QEHIMQEKMREXMZIYWISJ*EGIFSSOEWEQIXETLSVJSVXLIMRXIVEGXMSRWSJRIYVSRWMPPYWXVEXMRK MX[MXLEVVIWXMRKMQEKIW%FHYP7IWE]MRXVSHYGIHXLIZMWMXSVWXSXLI[SVPHSJLMKLXLVSYKLTYXWIUYIRGMRKGSRZI]MRKXLIGIRXVEP TPEGIXLEXXLMWXIGLRSPSK]LEWMRQSHIVRFMSQIHMGEPWGMIRGI 8LIVI[EWEGETEGMX]EYHMIRGISJZMWMXSVWSZIVX[SHE]WHVE[RJVSQPSGEPWGLSSPW8LIVI[EWEPWSEWIVMIWSJ[SVOWLSTW ERHHIQSRWXVEXMSRWWLS[MRKXLIMRXVMGEXITVSGIHYVIWIQTPS]IHMRYRHIVWXERHMRKXLIIEVP]HIZIPSTQIRXSJJVSKERH½WL IQFV]SWERHXLITVIGMWIXLMROMRKERHSFWIVZEXMSRVIUYMVIHXSWXYH]¾]KIRIXMGW4SWXIVTVIWIRXEXMSRWWLS[IHLMKLUYEPMX]MQEKIW JVSQGYVVIRX[SVOXSMRXVSHYGIXLIWXYHIRXWXSRI[WYFNIGXWERHXLIJEWXMHMSYWTVIWIRXEXMSRWXERHEVHWXLEXI\MWXMRWGMIRGIXSHE] MRC National Institute for Medical Research 31 PUBLIC OUTREACH Public engagement Professional development for teachers -R.YRI[ILIPHEQIIXMRKJSVPSGEPXIEGLIVWMR[LMGL[IJSGYWWIHSRXLVIIMHIEW[MXLEWTIGMEPTPEGIMRQSHIVRFMSQIHMGEP XLMROMRKXLIWMKRM½GERGISJTVSXIMRKVS[XLJEGXSVWMRWLETMRKGIPPJEXIXLIMQTSVXERGISJWXVYGXYVEPWXYHMIWSJTVSXIMRWERHLS[[I GSRGITXYEPMWIXLITVSGIWWIWF][LMGLXLIRIVZSYWW]WXIQTIVJSVQWMXWQMVEGYPSYWJYRGXMSRW 8LIXEPOW[IVI ;LEXHVMZIWJSVQEXMSRSJXLIRIVZSYWW]WXIQSJXLIKYX#8MJJER],IERYI ,S[TL]WMGEPQIXLSHWLIPTYWYRHIVWXERHLS[TVSXIMRWIRKMRIIVTVSKVEQQIHGIPPHIEXLERHSXLIVI\XVESVHMREV] FMSPSKMGEPEGXMZMXMIW8.6EKER *EGIFSSOEQIXETLSVJSVXLIQEQQEPMERRIVZSYWW]WXIQ)HI6ERG^ 8LIWTIEOIVWJSYRHI\EGXP]XLIVMKLXPIZIP[MXLWYJ½GMIRXRSZIPQEXIVMEPXSMRXIVIWXXIEGLIVWFYXRSXXSSJEVVIQSZIHJVSQXLI GYVVMGYPYQ8LIPMZIP]HMWGYWWMSRERH[VMXXIRVIWTSRWIWEJXIV[EVHWWYKKIWXXLIIZIRX[EWEKVIEXWYGGIWW'PSWIXSXIEGLIVW VIKMWXIVIHJSVXLIIZIRXGSQMRKJVSQHMJJIVIRXWGLSSPW Direct involvement in schools 2-16WXEJJTEVXMGMTEXIHMVIGXP]MRWGMIRGIIHYGEXMSRMRXLI7GMIRGI%QFEWWEHSVWWGLIQITVSZMHMRKEHMWXMRGXMZIIRVMGLQIRXXS GSQTPIQIRXXLIRSVQEPWGLSSPGYVVMGYPYQ7XEJJEVIEWOIHXSKMZIXEPOWEFSYXXLIMVVIWIEVGLSVSXLIVXSTMGWXS=IEVGPEWWIW JVSQXMQIXSXMQI7XEJJEVIEPWSMRZSPZIHMRI\XIRHIHTVSNIGXWVIUYMVIHJSVWSQI%PIZIPGSYVWIWEXX[SI\GIPPIRXPSGEPWGLSSPW ;ILEZIWIXYTTVSKVEQQIW[LIVI2-16WXEJJERW[IVUYIWXMSRWERHTYXWXYHIRXWSRXLIVMKLXXVEGO The University of the Third Age (U3A) at NIMR -R2SZIQFIV2-16LSWXIHXLIXIRXLREXMSREPQIIXMRKSJXLIWGMIRGIWIGXMSRSJXLI9%EWIPJQEREKIHSVKERMWEXMSR JSVVIXMVIHTISTPI[LSIRNS]PIEVRMRKEFSYXWGMIRGI1ER]XVEZIPUYMXIPSRKHMWXERGIWXSEXXIRH8LMW]IEVXLIXLIQI[EWJIXEP HIZIPSTQIRX[MXLXEPOWF]%PI\+SYPHSRFVEMRWTEVMRKERH1EPGSPQ0SKERSRPMQFHIZIPSTQIRX8LIVI[EWEGETEGMX]GVS[H SJRIEVP]IRXLYWMEWXW 32 MRC National Institute for Medical Research PUBLIC OUTREACH NIMRart a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´W0SRK0SER7GLIQIEPPS[MRKSTTSVXYRMXMIWXSI\LMFMX[SVOWF]JEQSYWERH IWXEFPMWLIHEVXMWXWMRSYVGSQQSRTYFPMGEVIEW8LMWGSQTPIQIRXWXLII\EQTPIWSFXEMRIHJVSQXLI2-16EVXTVSKVEQQIERHSYV S[RVSPPMRKI\LMFMXMSRHMWTPE]IHMRXLIGSVVMHSVWERHWXEMV[IPPWSJMQEKIWXEOIRJVSQGYVVIRXWGMIRXM½GTVSNIGXW Recent loans from the Arts Council Collection include (left to right) Eduardo Paolozzi, Caprese, bronze 1975, Basil Beattie, Cause and Effect V, acrylic on paper 1975, Colin Hall, Sunbather, cotton, gesso and acrylic 1978. Mill Hill Essays 7MRGI2-16LEWTVSHYGIHERERRYEPFSSOPIXSJIWWE]WXSMRGVIEWITYFPMGE[EVIRIWWSJXSTMGEPWGMIRXM½GMWWYIW;VMXXIRF] QIQFIVWSJWXEJJIEGLFSSOPIXMRGPYHIWEVERKISJXSTMGWVERKMRKJVSQIQIVKMRKMRJIGXMSRWXSWXIQGIPPWERHGPSRMRK8LI]EVI KMZIRXSZMWMXSVWERHHMWXVMFYXIHXSPSGEPWGLSSPWERHSXLIVSVKERMWEXMSRW PDF versions of all the published Mill Hill Essays can be accessed at: http://www.nimr.mrc.ac.uk/mill-hill-essays nimr i mrc ac uk/mill k/ hill essays MRC National Institute for Medical Research 33 Infections and Immunity Immune Cell Biology Immunoregulation Molecular Immunology Mycobacterial Research Parasitology Virology 34 MRC National Institute for Medical Research Victor Tybulewicz (Head of Division) Steve Ley Benedict Seddon Pavel Tolar Anne O’Garra (Head of Division) George Kassiotis Andreas Wack Gitta Stockinger (Head of Division) Venizelos Papayannopoulos Mark Wilson Douglas Young (Head of Division) Luiz Pedro de Carvalho Max Gutierrez Robert Wilkinson Tony Holder (Head of Division) Michael Blackman Delmiro Fernandez-Reyes Eva Frickel Jean Langhorne Jonathan Stoye (Head of Division) Kate Bishop John Doorbar John McCauley ;,3'SPPEFSVEXMRK'IRXVIJSV6IJIVIRGIERH6IWIEVGLSR-R¾YIR^E;-' INFECTIONS AND IMMUNITY Virology Kate Bishop Infection and replication of retroviruses 0EFQIQFIVW:MVKMRMI&SYGLIVMX3TLIPMI'SWRIJVS],EVVMIX+VSSQ(EVVIR;MKLX 6IXVSZMVYWIWGEYWIWIZIVIHMWIEWIWMRGPYHMRKMQQYRSHI½GMIRG] ERHGERGIV8LILYQERMQQYRSHI½GMIRG]ZMVYW,-:MWXLI QSWX[MHIP]ORS[RVIXVSZMVYWHYIXSMXWMQTEGXSRLYQER LIEPXL8LIPEXIWX½KYVIWVITSVXXLEXQMPPMSRTISTPIKPSFEPP] EVIPMZMRK[MXL,-:%-(7%FIXXIVYRHIVWXERHMRKSJXLI TSSVP]HI½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½IHTERHWLS[RXLEXMXHSIWRSXWIPJEWWSGMEXI MRWSPYXMSR;IEVIRS[YWMRKEZEVMIX]SJFMSGLIQMGEPERH ZMVSPSKMGEPXIGLRMUYIWXSMHIRXMJ]TMRXIVEGXMRKJEGXSVWERH GLEVEGXIVMWIXLIQIGLERMWQSJTJYRGXMSR-REHHMXMSR[I EVIYWMRKQMGVSWGST]XSZMWYEPMWITPSGEPMWEXMSRHYVMRKZMVEP VITPMGEXMSR Publications ;MKLX(.&SYGLIVMX:'2EHIV1%PPIR(.8E]PSV-%ERH&MWLST/2 The gammaretroviral p12 protein has multiple domains that function during the early stages of replication. Retrovirology 9:83 +VSSQ,'8ERH&MWLST/2 The tale of xenotropic murine leukemia virus-related virus. Journal of General Virology 93 +VSSQ,'8=ET1;+EPnS642IMP7.(ERH&MWLST/2 Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors. Proceedings of the National Academy of Sciences of the United States of America 107 Model for the function of p12 during the early stages of MLV replication. (A) Normally, infection results in integration of viral DNA into host chromatin. (B) Defects in the N-terminal domain of p12, E-A, affect the stability of the viral core and abort infection very early in the replication pathway. (C) Alterations to the C-terminal domain of p12, E-B, prevent p12 from tethering the pre-integration complex to host chromatin, inhibiting integration. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 35 INFECTIONS AND IMMUNITY Parasitology Mike Blackman Proteases in host cell exit and invasion by the malaria parasite 0EFQIQFIVW'LVMWXMRI'SPPMRW7YNEER(EW*MSRE,EGOIXX6SFIVX1SSR1EVME4IR^S6SFIVX7XEPPQEGL1EPGSPQ7XVEXL 'EXLIVMRI7YEVI^'LVMWPEMRI;MXLIVW1EVXMRI^'LVMWXMEERZER3SMN 1EPEVMEGEYWIWMQQIRWIWYJJIVMRKOMPPMRKEXPIEWXSRIQMPPMSRTISTPIIEGL]IEVERHMW EQENSVGSRXVMFYXSVXSTSZIVX]8LIHMWIEWIMWGEYWIHF]EWMRKPIGIPPIHTEVEWMXIERH MWWTVIEHF]QSWUYMXSIW8LIVIMWRSQEPEVMEZEGGMRIERHVIWMWXERGIEKEMRWXQEMRWXE] ERXMQEPEVMEPHVYKWMW[MHIWTVIEH8LIVIMWERIIHXS½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ublications 1SSR6;,EPP.6ERKOYXM*,S=7%PQSRH2 1MXGLIPP+,4EMR%,SPHIV%%ERH&PEGOQER1. Adaption of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes. Proceedings of the National Academy of Sciences 110: 6YIGOIV%7LIE1,EGOIXX*7YEVI^',MVWX)1% 1MPYXMRSZMG/;MXLIVW1EVXMRI^'ERH&PEGOQER1. Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte. Journal of Biological Chemistry 287 3PMZMIVM%'SPPMRW'6,EGOIXX*;MXLIVW1EVXMRI^' 1EVWLEPP.*P]RR,67OILIP.1ERH&PEGOQER1. Juxtamembrane shedding of Plasmodium falciparum AMA1 is sequence independent and essential, and helps evade invasion-inhibitory antibodies. PLoS Pathogens 7I Molecular model of the active site of PfSUB1, a subtilisin-like protease involved in malaria parasite release from its red cell. A peptide substrate is shown docked into the active site cleft. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 36 MRC National Institute for Medical Research -QQYRS¾YSVIWGIRGIMQEKIWLS[MRKMRXVEGIPPYPEV malaria merozoites covered with an invasion-related protein called AMA1 (green). Another important protein called EBA175 (red) is still within merozoite secretory organelles called micronemes. Parasite nuclei are stained blue. INFECTIONS AND IMMUNITY Mycobacterial Research Luiz Pedro de Carvalho Mycobacterium tuberculosis systems and chemical biology 0EFQIQFIVW8MQSXL]/IRGL,ERME/LSYV]+qVEPH0EVVSY]1EYQYW-IZE4EPYFIGOEMXI+EVIXL4VSWWIV The recent dissemination of strains of Mycobacterium tuberculosis1XFVIWMWXERXXSQYPXMTPIHVYKWGSRWXMXYXIW EQENSVLIEPXLXLVIEX1EROMRHQMKLXWSSRJEGIXLI½VWX ITMHIQMGSJYRXVIEXEFPIXYFIVGYPSWMW1YPXMHVYKVIWMWXERGI EVMWIWERHMWWIPIGXIHJSVFIGEYWISJXLIGSQTPI\KVS[XL TEXXIVRSJ1XFMXWI\XVIQIEHETXEXMSRXSXLILSWXERH FIGEYWII\MWXMRKXLIVETMIWEVI¾E[IH4EWXQ]GSFEGXIVMEP ERHERXMQ]GSFEGXIVMEPVIWIEVGLTVSKVEQQIWLEZIGPIEVP] RSXFIIRWYJ½GMIRXP]IJJIGXMZIEXTVSZMHMRKRSZIPXLIVETMIW XLEXGSYPHVIZIVWIXLMWXVIRH2SZIPETTVSEGLIWERH XIGLRSPSKMIWEVIYVKIRXP]RIIHIHXSEZSMHEKPSFEPLIEPXL GEXEWXVSTLI Our work has demonstrated that biochemistry and FMSEREP]XMGEPGLIQMWXV]GERPIEHXSFIXXIVYRHIVWXERHMRK SJTLIRSX]TIWERHXEVKIXWERHXLIVEXMSREPHIWMKRERH WXYH]SJRSZIPERXMFEGXIVMEPEKIRXW;ILEZIGSQTPIXIH EXLSVSYKLGLEVEGXIVM^EXMSRSJXLIEPPSWXIVMGMRLMFMXMSR QIGLERMWQSJ1XF%84TLSWTLSVMFSW]PXVERWJIVEWIWII ½KYVIERIWWIRXMEPIR^]QIMR0LMWXMHMRIFMSW]RXLIWMW %PPSWXIVMGMRLMFMXSVWERHEGXMZEXSVWEVIGYVVIRXP]FIMRK GLEVEGXIVMWIH;ILEZIEPWSVIGIRXP]ETTPMIHEGXMZMX] FEWIHQIXEFSPSQMGTVS½PMRKXSMHIRXMJ]XLI½VWXKP]GIVSP TLSWTLEXITLSWTLEXEWIJVSQ1XF8LMWIR^]QIETTIEVW XSFIMRZSPZIHMRPMTMHTSPEVLIEHQIXEFSPMWQERIWWIRXMEP GSQTSRIRXSJTPEWQEQIQFVERIFMSW]RXLIWMWERH VIQSHIPPMRK Publications 1ES'7LYOPE10EVVSY]1EYQYW+(M\*0/IPPI]0%7XIVRFIVK1.7SFVEP&;HI 'EVZEPLS04 Functional assignment of Mycobacterium tuberculosis proteome revealed by genome-scale fold-recognition. Tuberculosis 93: 4IHVIyS74MWGS.40EVVSY]1EYQYW+/IPP]+ERHHI'EVZEPLS047 Mechanism of feedback allosteric inhibition of ATP phosphoribosyltransferase. Biochemistry 51¯ HI'EVZEPLS047>LES,(MGOMRWSR')%VERKS210MQE'(*MWGLIV713YIVJIPPM3 2EXLER'ERH6LII/= %GXMZMX]FEWIHQIXEFSPSQMGTVS½PMRKSJIR^]QEXMGJYRGXMSRMHIRXM½GEXMSRSJ6ZG as a mycobacterial 2-hydroxy-3-oxoadipate synthase. Chemistry & Biology 17 Characterisation of the mechanism of allosteric inhibition of Mycobacterium tuberculosis ATP phosphoribosyltransferase. Combination of X-ray crystallography, steady-state and pre-steady state kinetics, pH studies and saturation transfer NMR spectroscopy. 7IIVIJIVIRGIERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 37 INFECTIONS AND IMMUNITY Virology John Doorbar Human papillomavirus biology and disease 0EFQIQFIVW'PEVI(EZ],IEXLIV+VMJ½R1MGLEIP-SERRSY(IFSVEL.EGOWSR4EYPMRI1G-RXSWL)QMPMS4EKPMEVYPS=EWQMRE7SRINM 'LVMWXMRE9RXIVWTIVKIV5MER;ERK>LSRKPMR;Y ,YQERTETMPPSQEZMVYWIW,4:GEYWIEVERKISJWMKRM½GERX LYQERHMWIEWIWMRGPYHMRKPEV]RKIEPTETMPPSQEXSWMWKIRMXEP[EVXW ERHGIVZMGEPRISTPEWME'IVXEMR,4:X]TIWORS[REWLMKL VMWOX]TIWGEYWIGIVZMGEPPIWMSRWXLEXGERTVSKVIWWXSGERGIV 'IVZMGEPGERGIVMWEQENSVJIQEPIGERGIV[SVPH[MHIERHMW EPQSWXEP[E]WGEYWIHF],4:8LIWIZMVYWIWGEREPWSGEYWI EWMKRM½GERXTVSTSVXMSRSJLIEHERHRIGOXYQSYVWERHLEZI FIIRMQTPMGEXIHMRXLIHIZIPSTQIRXSJWSQIRSRQIPERSQE WOMRGERGIVW,S[XLIFSH]GSRXVSPWMRJIGXMSRMWTSSVP] YRHIVWXSSHERHGYVVIRXP]XLIVIMWRSERXMZMVEPXLIVET]XLEXGER VIPMEFP]GPIEVMRJIGXMSR Publications -WEEGWSR;IGLWPIV);ERK56SFIVXW-4EKPMEVYPS) .EGOWSR(9RXIVWTIVKIV''SPIQER2+VMJ½R,ERH (SSVFEV. Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/ E7 deregulation and the loss of contact inhibition in neoplastic progression. Journal of Virology 86 /LER.(EZ]')1G-RXSWL4&.EGOWSR(.,MR^7;ERK5 ERH(SSVFEV. The role of calpain in the formation of HPV16 E1^E4 EQ]PSMH½FIVWERHVISVKERM^EXMSRSJXLIOIVEXMRRIX[SVO Journal of Virology 85¯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ersistence of viral DNA in the epithelial basal layer suggests a model for papillomavirus latency following immune regression Virology 414 7IIVIJIVIRGIWERH MRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYT MR 38 MRC National Institute for Medical Research Working model of HPV Latency as outlined in Maglennon at al (2011) Virology 414 p153-163. Lesion GPIEVERGIMRZSPZIWXLIWLYXSJJSJZMVEPKIRII\TVIWWMSREWP]QTLSG]XIWMR½PXVEXI INFECTIONS AND IMMUNITY Parasitology Delmiro Fernandez-Reyes Pathogenesis of childhood severe malaria 0EFQIQFIVW7EQYIP%FEL(MQMXVMSW%XLEREWEOMW*PSVIRGI&YVXI-ERMRE'SRXI&EVV])P].YLS6SYWY3PYKFIQMVS7SHIMRHI ,EPJSJXLI[SVPHTSTYPEXMSRMWEXVMWOSJQEPEVME,YQER QEPEVMEGEYWIHF]Plasmodium falciparumVITVIWIRXWEKPSFEP HMWIEWIFYVHIR[MXLERIWXMQEXIHQMPPMSRGPMRMGEPITMWSHIW TIV]IEVPIEHMRKXSEVSYRHSRIQMPPMSRHIEXLW'IVIFVEPQEPEVME ERHWIZIVIQEPEVMEPEREIQMEEVIFSXLQENSVGSQTPMGEXMSRW [MXLWMKRM½GERXQSVXEPMX]ERHQSVFMHMX]MRGLMPHVIRYRHIV ½ZI]IEVWSJEKIMR7YF7ELEVER%JVMGE;IEVIJSGYWIHSR XLIWXYH]SJWIZIVIQEPEVMEW]RHVSQIWMRGLMPHVIREXXIRHMRK XIVXMEV]LSWTMXEPWMRHIRWIP]TSTYPEXIHLSPSIRHIQMGQEPEVME EVIEW1EPEVMETEXLSKIRIWMWGEYWIHF]XLITEVEWMXI´WEWI\YEP IV]XLVSG]XMGG]GPIPEVKIP]SGGYVWMRXLIZEWGYPEVGSQTEVXQIRX ;IEVIMRXIVIWXIHMRFSXLXLIVSPISJIRHSXLIPMEPGIPPEGXMZEXMSR ERHXLITPEWQETVSXISQIGLERKIWXLEXSGGYVHYVMRKHMWXMRGX WIZIVIQEPEVMETVIWIRXEXMSRW ;IGEVVMIHSYXEPEVKIGEWIGSRXVSPTPEWQETVSXISQI WXYH]SJGLMPHLSSHWIZIVIQEPEVMEMRGPYHMRKHMWGSZIV]ERH ZEPMHEXMSRGSLSVXWEXXLIQEMRXIVXMEV]LSWTMXEPSJXLIGMX]SJ -FEHER2MKIVMEYRHIVXLIEYWTMGIWSJXLI'LMPHLSSH1EPEVME 6IWIEVGL+VSYT3YVGPMRMGEPTVSXISQMGWWXYH]WLS[WXLEX TPEWQETVSXISQITVS½PIWEGGYVEXIP]HMWGVMQMREXIWIZIVI GLMPHLSSHQEPEVMEJVSQYRGSQTPMGEXIHGEWIWEW[IPPEWJVSQ MPPERHLIEPXL]QEPEVMERIKEXMZIGLMPHVIR8LIHI½RIHTPEWQE TVSXISQITEXXIVRWEVIGSQTSWIHSJEGSQFMREXMSRSJWIZIVEP HMJJIVIRXMEPP]I\TVIWWIHTVSXIMRWXLEXEGXEWFMSQEVOIVWSJXLI WIZIVIQEPEVMEHMWIEWITVSGIWW Publications %NIXYRQSFM;%3VMQEHIKYR%)&VS[R&.%JSPEFM2/3PEFM]M*%%RIXSV.-3QSOLSHMSR 73WMRYWM/%OMRFEQM*37LSOYRFM;7SHIMRHI3ERH*IVRERHI^6I]IW( Haemoglobinuria among children with severe malaria attending tertiary care in Ibadan, Nigeria. Malaria Journal 11:336 7ERHLY+&EXXEKPME*)P]&/%XLEREWEOMW(1SRXS]E6:EPIRGME8+MPQER6,)ZERW'% *VMIHPERH.7*IVRERHI^6I]IW(ERH%KVERSJJ(( Discriminating active from latent tuberculosis in patients presenting to community clinics. PLOS ONE 7:e38080 Scatter plot of mean age-group parasite density vs. mean age-group prevalence in urban west Africa, 2004-2011. 1EPEVMETEVEWMXITVIZEPIRGIVMWIW[MXLEKIMRXLIYRHIV½ZIWHVSTWMR early childhood but remains high in older children. The high prevalence ½KYVIWEGVSWWEPPEKIKVSYTWEVIELIEZ]FYVHIRSRGLMPHLIEPXL 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR MRC National Institute for Medical Research 39 INFECTIONS AND IMMUNITY Parasitology Eva Frickel A new perspective on anti-Toxoplasma gondii immunity 0EFQIQFIVW&EVFEVE'PSYKL'PIQIRGI*SPX^%WLPIMKL.SLRWXSR1MGLEIP0YOYQFY^]E%RRE7ERIGOE(YMR 8LITVSXS^SERTEVEWMXI Toxoplasma gondii MRJIGXWEFVSEHVERKISJLSWXW[MXLE WIVSTVIZEPIRGIMRQERSJEFSYXToxoplasmaQEMRXEMRWERMRXVMGEXIFEPERGI FIX[IIRMXWS[RWYVZMZEPERHLSWXHIJIRGIXSEGLMIZIGLVSRMGMX]-*2aXLIQEMR G]XSOMRIVIWTSRWMFPIJSVMXWGSRXVSPEGXMZEXIWGIPPWXSVIWXVMGXMRXVEGIPPYPEVTEVEWMXI VITPMGEXMSRSVXSOMPPMRXVEGIPPYPEVToxoplasma'IPPQIHMEXIHMQQYRMX]HVMZIRQSWXP]F] '(8GIPPWGSRJIVWVIWMWXERGIXSXLIGLVSRMGTLEWISJXLITEVEWMXI8LISYXGSQISJER infection with ToxoplasmaMWHIXIVQMRIHRSXSRP]F]XLILSWX´WMQQYRIWXEXYWFYXEPWS F]XLIKIRSX]TISJXLIMRJIGXMRKWXVEMRToxoplasmaTEXLSKIRIWMWVIWYPXWJVSQTEVEWMXI FYVHIRGSRGYVVIRX[MXLERSZIVWXMQYPEXMSRSJXLIMQQYRIW]WXIQMRXLIJSVQSJLMKL PIZIPWSJ8LIPTIVGIPPX]TIG]XSOMRIW 3YVPSRKXIVQKSEPMWXSMHIRXMJ]RSZIPTEXL[E]WERHQIGLERMWQWSJLSWXVIWMWXERGI to Toxoplasma;IEVIWXYH]MRKLS[XLITEVEWMXSTLSVSYWZEGYSPI4:MWVIQSHIPPIH [MXLMRLSWXGIPPWXSPMQMXTEVEWMXIVITPMGEXMSREW[IPPEWLS[ToxoplasmaQERMTYPEXIW XLIMQQYRIW]WXIQXSQSYRXERIJ½GMIRXFYXRSXHIXVMQIRXEP'(8GIPPVIWTSRWI ;IEVIWTIGM½GEPP]MRXIVIWXIHMRXLIJYRGXMSREPGSRWIUYIRGIWSJZEGYSPEVVIGSKRMXMSR by IFNaYTVIKYPEXIHT+84EWIW+&4WE]IXYRHIVWXYHMIHGPEWWSJVIKYPEXSV] TVSXIMRW%HHMXMSREPP][IEVIHI½RMRKXLIVIUYMVIQIRXWJSVVIGSKRMXMSRERHJYRGXMSREP consequences of ToxoplasmaERXMKIRWTIGM½G'(8GIPPWMRXLIGLVSRMGTLEWISJ MRJIGXMSRMRXLIFVEMR Publications ;MRXIV7:2MIHIPQER;.IRWIR/(6SWS[WOM)).YPMIR0 7TSSRIV)'EVEHSRRE/&YVPIMKL&%7EIMN.4.4PSIKL,0 ERH*VMGOIP)1 Determinants of GBP recruitment to Toxoplasma gondii vacuoles and the parasitic factors that control it. PLoS ONE 6I /MVEO3*VMGOIP)1+VSXIRFVIK+17YL,.EIRMWGL6ERH 4PSIKL,0 8VERWRYGPIEVQMGI[MXLTVIHI½RIH8GIPPVIGITXSV WTIGM½GMXMIWEKEMRWXToxoplasma gondii obtained via SCNT. Science 328 *VMGOIP)17ELSS2,STT.+YFFIPW1.'VEZIV14./RSPP 0.4PSIKL,0ERH+VSXIRFVIK+1 4EVEWMXIWXEKIWTIGM½GVIGSKRMXMSRSJIRHSKIRSYW Toxoplasma gondii-derived CD8+ T cell epitopes. Journal of Infectious Diseases 198 7IIVIJIVIRGIMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSR JVSQXLMWKVSYTMR 40 MRC National Institute for Medical Research T cell receptor (TCR) sequences of three distinct lines of mice that recognise the same peptide-MHC complex. With these, we are investigating how MHC-TCR interactions dictate memory CD8 phenotypes. Toxoplasma enters nucleated cells via active invasion. It is unclear how the host restricts the parasitophorous vacuole to limit parasite replication and facilitate antigen presentation to CD8 T cells. INFECTIONS AND IMMUNITY Mycobacterial Research Max Gutierrez Cell biology of M. tuberculosis infection 0EFQIQFIVW8LSQEW0IVRIV0EYVE7GLRIXXKIV 8SPMZI[MXLMRIYOEV]SXMGGIPPWM. tuberculosisLEWHIZIPSTIH XLVSYKLIZSPYXMSRERMQTVIWWMZIWIXSJQSPIGYPEVXSSPW1ER] GPMRMGEPQERMJIWXEXMSRWERHTVSFPIQWHYVMRKXVIEXQIRXSJ XYFIVGYPSWMWEVIEHMVIGXGSRWIUYIRGISJETSTYPEXMSRSJ MRXVEGIPPYPEVFEGMPPM%PXLSYKLin vitro and in vivo studies have WLIHPMKLXSRWSQIEWTIGXWSJXYFIVGYPSWMWTEXLSKIRIWMW [IWXMPPHSRSXGSQTPIXIP]YRHIVWXERHLS[M. tuberculosis QEREKIWXSWYVZMZIMRIYOEV]SXMGGIPPW;IFIPMIZIXLEXE HIXEMPIHYRHIVWXERHMRKSJLSWXQ]GSFEGXIVMEMRXIVEGXMSRW[MPP TVSZMHIMRWMKLXWRSXSRP]MRXSXLIQIGLERMWQWYWYVTIHF] Q]GSFEGXIVMEXSWYVZMZIFYXEPWSMRXSFEWMGEWTIGXWSJGIPPYPEV JYRGXMSRWERHMRXLIMRREXIMQQYRIW]WXIQ 6IWIEVGLMRSYVKVSYTJSGYWIWSRXLIQIGLERMWQW[LIVIF] M. tuberculosisEVVIWXWTLEKSWSQIQEXYVEXMSRERHEZSMHW OMPPMRKF]QEGVSTLEKIWERHRSRTLEKSG]XMGGIPPW8S[EVHWXLMW KSEP[IWXYH]XLIMRXVEGIPPYPEVXVERWTSVXSJM. tuberculosis MRQEGVSTLEKIWITMXLIPMEPERHIRHSXLIPMEPGIPPW;ILEZI MHIRXM½IHRSZIPJEGXSVWMRZSPZIHMRZIWMGYPEVXVEJ½GOMRKERH TVSXIMRWSVXMRKTEVXMGYPEVP]TLEKSP]WSWSQIJYWMSRHYVMRK MRJIGXMSR8LIWITVSXIMRWEVITVSQMWMRKGERHMHEXIWJSVFIMRK MRZSPZIHMRXLIP]WSWSQEPQIHMEXIHOMPPMRKSJM. tuberculosis, EW[IPPEWMRXLIQSPIGYPEVIZIRXWPMROMRKMRREXIERHEHETXMZI MQQYRIVIWTSRWIW;IEVIGYVVIRXP]GLEVEGXIVMWMRKXLIVSPI TPE]IHF]XLIWITVSXIMRWHYVMRKXLIHIZIPSTQIRXSJMRREXIERH EHETXMZIMQQYRIVIWTSRWIW Publications 4IM+&VSRMIX^OM1ERH+YXMIVVI^1+ Immune regulation of Rab proteins expression and intracellular transport. Journal of Leukocyte Biology 92 HI7SY^E'EVZEPLS'/EWQETSYV&+VSRS[%6SLHI16EFMRSZMXGL1ERH+YXMIVVI^1+ Internalization, phagolysosomal biogenesis and killing of mycobacteria in enucleated epithelial cells. Cellular Microbiology 13 Endothelial cells infected with mycobacteria expressing GFP. Bacteria are shown in green, actin cytoskeleton (rhodamine-phalloidin staining) in red and nuclei (DAPI staining) in blue. /EWQETSYV&+VSRS[%&PIGO'/),SRK;ERH+YXMIVVI^1+ Size-dependent mechanism of cargo sorting during lysosome-phagosome fusion is controlled by Rab34. Proceedings of the National Academy of Sciences of the United States of America 109 MRC National Institute for Medical Research 41 INFECTIONS AND IMMUNITY Parasitology Tony Holder Malaria parasites and red blood cells 0EFQIQFIVW7YVE]E(ME^1YRM+VEMRKIV.YHMXL+VIIR'PEMVI,EWXMRKW1EHLY/EHIOSTTEPE)PPIR/RYITJIV6SFIVX1SSR7SPE 3KYR/EZIVM6ERKEGLEVM7LMKILEVY7EXS=YOMXE7EXS2SSV%^MER=YWYJ 1EPEVMEMWGEYWIHF]ETEVEWMXMGTVSXS^SERXLEXMRZEHIW VIHFPSSHGIPPW[LIVIMXHIZIPSTWERHQYPXMTPMIWFIJSVI FYVWXMRKSYXERHMRZEHMRKJVIWLVIHGIPPW8LMWG]GPIMW VIWTSRWMFPIJSVXLIHMWIEWI9RHIVWXERHMRKXLIMRXIVEGXMSR between the parasite and the host immune system GSRXVMFYXIWXSXLIHIZIPSTQIRXSJEQEPEVMEZEGGMRI8LI MHIRXM½GEXMSRSJRI[XEVKIXWJSVHVYKWXSOMPPXLITEVEWMXI ERHMRXIVVYTXXLIG]GPISJQYPXMTPMGEXMSRSJJIVWXLITSXIRXMEP SJRI[XLIVETIYXMGMRXIVZIRXMSRW -RSRIEVIESJVIWIEVGL[ILEZIJSGYWIHSRXLITVSXIMRW JSYRHSRXLIWYVJEGISJXLIQIVS^SMXIJSVQSJXLITEVEWMXI XLEXMWVIPIEWIHJVSQXLIMRJIGXIHVIHFPSSHGIPP8LIWI TVSXIMRWQE]FIVIWMHIRXSVTIVMTLIVEPQIQFVERITVSXIMRW ERHWSQIEVIWIGVIXIHSYXJVSQMRXIVREPSVKERIPPIWNYWX FIJSVIFMRHMRKERHMRZEWMSRSJERI[VIHFPSSHGIPP8LI] JSVQPEVKIQYPXMGSQTSRIRXGSQTPI\IW[LMGLEVIEPWS JYVXLIVQSHM½IHF]TSWXXVERWPEXMSREPQSHM½GEXMSRWYGL EWTVSGIWWMRKF]TVSXIEWIW7SQISJXLITVSXIMRWQIHMEXI FMRHMRKXSLSWXPMKERHWETVSGIWW[LMGLMWIWWIRXMEPJSV VIHGIPPVIGSKRMXMSRERHMRZEWMSR8LIWIMRXIVEGXMSRWQE] FIHMWVYTXIHF]LSWXERXMFSH]ERHXLITEVEWMXIXEVKIXWSJ XLIWIERXMFSHMIWEVIGERHMHEXIWJSVZEGGMRIHIZIPSTQIRX Publications &IPP%71MPPW.);MPPMEQW+4&VERRMKER.%;MPOMRWSR%. 4EVOMRWSR80IEXLIVFEVVS[6.8EXI);,SPHIV%%ERH 7QMXL(* Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs. PLoS Neglected Tropical Diseases 6I +YXXIV](74SYPMR&*IVKYWSR(.47^SSV&;MGOWXIEH &'EVVSPP406EQEOVMWLRER'&VEH](4EX^I[MX^)1 7XVEWGLMP97SP]EOSZ0+VIIR.07MRHIR6)8SFMR%& ,SPHIV%%ERH8I[EVM6 A unique protein phosphatase with kelch-like domains (PPKL) in Plasmodium modulates ookinete differentiation, motility and invasion. PLoS Pathogens 8I 1SWW(/6IQEVUYI).*EFIV&;'EZEREKL(6%VRSX ()8LSQEW%;ERH,SPHIV%% Plasmodium falciparum 19-kilodalton merozoite surface TVSXIMR174WTIGM½GERXMFSHMIWXLEXMRXIVJIVI with parasite growth in vitro can inhibit MSP1 processing, merozoite invasion and intracellular parasite development. Infection and Immunity 80 7IIVIJIVIRGIW ERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR 42 MRC National Institute for Medical Research Parasite antigens recognised by antibodies from children and adults living in a malaria endemic area. Immune adults have antibodies reacting with a larger spectrum of proteins compared with the non-immune children. Merozoites are among the smallest eukaryotic cells and invade red blood cells. The apical rhoptry and microneme organelles facilitate invasion driven by an actomyosin motor located on the inner membrane complex. INFECTIONS AND IMMUNITY Immunoregulation George Kassiotis Antiviral immunity 0EFQIQFIVW9VW^YPE)OWQSRH1MGSP*IVVS7XITLIR0EQ&IXXMRE1EZVSQQEXMW.YPME1IVOIRWGLPEKIV+ISVKMRE8LSVFSVR +ISVKI=SYRK -RJIGXMSYWHMWIEWIWGEYWIEUYEVXIVSJEPPHIEXLW[SVPH[MHIERHMRGERGIVW 'IVXEMRZMVYWIWGEYWIEGYXIMRJIGXMSRWMRLYQERW[LMGLGERFIVETMHP]JEXEP[MXLMR HE]WJSVI\EQTPIMR¾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½GMIRG]EPPS[WXLIIWXEFPMWLQIRXSJJYPP]MRJIGXMSYWZMVYWIW[LMGLYPXMQEXIP]GEYWI GERGIVMRQMGI8LIWITEXLSKIRMGZMVYWIWEVIXLIVIWYPXSJVIGSQFMREXMSRFIX[IIR )6:TVIGYVWSVW *YPPKIRSQIWIUYIRGIGSQTEVMWSRFIX[IIRMRJIGXMSYWVIXVSZMVYWIWJSYRHMRMQQYRIHI½GMIRXQMGI and their endogenous precursors. Publications (YPI]%/4PSUYMR1.=)OWQSRH9%QQERR'+1IWWIV6. 1]IVW0,EWIROVYK/.ERH/EWWMSXMW+ Negative impact of IFN-a on early host immune responses to retroviral infection. Journal of Immunology 189 =SYRK+6)OWQSRH97EPGIHS6%PI\STSYPSY07XS]I.4ERH /EWWMSXMW+ Resurrection of endogenous retroviruses in antibodyHI½GMIRXQMGI Nature 491 =SYRK+64PSUYMR1.)OWQSRH9;EH[E17XS]I.4ERH /EWWMSXMW+ Negative selection by an endogenous retrovirus promotes a higher-avidity CD4+ T cell response to retroviral infection. PLoS Pathogens 8I Numerous retroviral particles (pseudocoloured) in the extracellular spaces of a lymphoma resected JVSQEP]QTLSG]XIHI½GMIRX6EK-/- mouse. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 43 INFECTIONS AND IMMUNITY Parasitology Jean Langhorne Immunity and immunopathogenesis in malaria infections 0EFQIQFIVW8LMFEYX&VYKEX(IMVHVI'YRRMRKLEQ;MPPMEQ.EVVE7EVEL/IPPIV1G0EYKLPMR:MGXSV/SYEWWM6EGLIP0E[VIRGI4VMWGE 0IZ];MIFOI2ELVIRHSVJ(EQMER4IVI^1E^PMEL7STLMI6SIX]RGO.ER7SHIROEQT4LMPMT7TIRGI-VIRI8YQ[MRI ;IWXYH]XLIMQQYRIVIWTSRWIXSXLIQEPEVMETEVEWMXIERH XLIVSPIMXTPE]WMRXLIHIZIPSTQIRXSJWIZIVIQEPEVMEHMWIEWI 8LMWMRZSPZIWMHIRXM½GEXMSRSJXLIOI]GSQTSRIRXWSJMRREXI ERHEHETXMZIMQQYRMX]XLEXGSRXVSPERHIPMQMREXITEVEWMXIW ERHVIKYPEXIMQQYRSTEXLSPSK]%WIGSRHEWTIGXSJSYV[SVO MWXSMHIRXMJ]TEVEWMXIQSPIGYPIWSRXLIWYVJEGISJXLIMRJIGXIH IV]XLVSG]XIWXLEXQE]FIVIWTSRWMFPIJSVERXMKIRMGZEVMEXMSR ERHJSVFMRHMRKSJXLITEVEWMXIXSLSWXIRHSXLIPMYQERHMRXLMW [E]GSRXVMFYXIXSTEXLSPSK] %FEPERGIFIX[IIRTVSERHERXMMR¾EQQEXSV]VIWTSRWIW MWGVMXMGEPJSVGSRXVSPPMRKQEPEVMETEVEWMXIWERHLSWXWYVZMZEP -0EOI]VIKYPEXSV]G]XSOMRITVSHYGIHF]QER]MQQYRI GIPPWTVSXIGXWQMGIEKEMRWXTEXLSPSK]HYVMRKEGYXIPlasmodium chabaudMQEPEVME;ILEZIWLS[RXLEX8GIPPHIVMZIH-0 MWRIGIWWEV]XSGSRXVSPQEPEVMETEXLSPSK]QMGIGEVV]MRK EHIPIXMSRSJXLIIL10KIRIMR8GIPPWWLS[[IMKLXPSWW L]TSXLIVQMEERHMRGVIEWIHQSVXEPMX]%PXLSYKL*S\T VIKYPEXSV]'(8GIPPWTVSHYGI-0HYVMRKMRJIGXMSRLMKLP] EGXMZEXIH-*2a8LGIPPWEVIXLIGVMXMGEPWSYVGISJTVSXIGXMZI -08LIKIRIVEXMSRSJXLIWITVSXIGXMZI-08LGIPPWMW HITIRHIRXSR-0 Publications *VIMXEWHS6SWjVMS%4 0EQF8 7TIRGI4 7XITLIRW6 0ERK% 6SIVW% 1YPPIV; 3´+EVVE%ERH 0ERKLSVRI. IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. Journal of Immunology 188 1EWXIPMG& *VIMXEWHS6SWEVMS%4:IPHLSIR1 6IREYPH.' .EVVE; 7TSREEW%1 6SIX]RGO7 7XSGOMRKIV&ERH0ERKLSVRI. IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Frontiers in Immunology 3:85 7TIRGI4.ERH0ERKLSVRI. T cell control of malaria pathogenesis. Current Opinion in Immunology 24, 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR 44 MRC National Institute for Medical Research INFECTIONS AND IMMUNITY Immune Cell Biology Steve Ley Regulation of immune responses by NF-gB and MAP kinases 0EFQIQFIVW,EOIQ&IR%HHM'LES7LIRK'LIR8LSVWXIR+ERXOI)ZE+YIGOIP)QMPMI.EGUYI.YPME.ER^IR%KRIW1EQFSPI 3PMZME1MXGLIPP1EXSYPE4ETSYXWSTSYPSY 8LIMRREXIMQQYRIVIWTSRWISJQEQQEPWMWXLI½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¾EQQEXSV]HVYKXEVKIXMRQYPXMTPIWGPIVSWMW Publications +ERXOI87VMWOERXLEVENEL77EHS[WOM1ERH0I]7' IgB kinase regulation of the TPL-2/ERK MAPK pathway. Immunological Reviews 246 6SKIX/&IR%HHM%1EQFSPI(IQE%+ERXOI8=ERK,8 .ER^IR.1SVVMGI2%FFSXX(ERH0I]7' IKK2 regulates TPL-2 activation of ERK-1/2 MAP kinases by direct phosphorylation of TPL-2 serine 400. Molecular and Cellular Biology 32 =ERK,84ETSYXWSTSYPSY7&IPMGL1&VIRHIV'.ER^IR. +ERXOI8,ERHPI]1ERH0I]7' Coordinate regulation of TPL-2 and NF-gB signaling in macrophages by NF-gB1 p105. Molecular and Cellular Biology 32 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EX XLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR Regulation of TPL-2 by IgB kinase and NF-gB1 p105 In unstimulated cells, TPL-2 is held in an inactive state by its association with p105. Following infection, TPL-2 and p105 are phosphorylated by IgB kinase inducing p105 degradation, releasing TPL-2 from p105-mediated inhibition and inducing TPL-2 signalling activity. MRC National Institute for Medical Research 45 INFECTIONS AND IMMUNITY Virology John McCauley ,SWXWTIGM½GMX]SJMR¾YIR^EZMVYWIW 0EFQIQFIVW1MGLEIP&IRRIXX(SREPH&IRXSR7EMVE,YWWEMR7XIZI;LEVXSR -R¾YIR^E%ZMVYWIWMRJIGXEZEVMIX]SJWTIGMIW[MXLLYQERW LSVWIWERHTMKWVITVIWIRXMRKXLIQEMRQEQQEPMERLSWXW SJXLIZMVYWMR[LMGLMRJIGXMSRMWWYWXEMRIH%ZMERWTIGMIW TEVXMGYPEVP][EXIVJS[PERHKYPPWLEVFSYVE[MHIZEVMIX]SJ MR¾YIR^E%ZMVYWIWHI½RIHF]XLIMVLEIQEKKPYXMRMR,ERH RIYVEQMRMHEWI2KP]GSTVSXIMRWYFX]TIWMREZEVMIX]SJ,2 GSQFMREXMSRW2I[TERHIQMGWXVEMRWSJLYQERMR¾YIR^EZMVYW EVMWIJVSQERERMQEPVIWIVZSMVIMXLIVHMVIGXP]EWJSVXLI TERHIQMG%,2ZMVYWSVEWEVIWYPXSJKIRIVIEWWSVXQIRX FIX[IIRELYQERERHERERMQEPMR¾YIR^EZMVYWEWMRXLI ERHTERHIQMGW ;IEVIMRZIWXMKEXMRKXLIHIXIVQMRERXWSJLSWXVERKIVIWXVMGXMSR SJEZMERERHW[MRIMR¾YIR^EZMVYWIWXLEXPMQMXXLIMVEFMPMX]XS MRJIGXERHTVSTEKEXIMRLYQERGIPPW8LIMRXIVEGXMSRFIX[IIREZMVYWTEVXMGPIERHMXWVIGITXSVSRELSWXGIPPMWEOI]JIEXYVIXLEX PMQMXWXLILSWXVERKISJMR¾YIR^EZMVYWIWFYXEHHMXMSREPJEGXSVWJSPPS[MRKIRXV]SJZMVYWMRXSXLIGIPPEPWSGSRXVSPXLISYXGSQISJ MRJIGXMSR6IGIRXLYQER,2ZMVYWIWWLS[YRI\TIGXIHVIGITXSVFMRHMRKEGXMZMXMIW8LIGLEVEGXIVMWXMGWSJXLMWFMRHMRKEVIFIMRK I\EQMRIHMRGSPPEFSVEXMSR[MXLGSPPIEKYIWMRXLI(MZMWMSRWSJ4L]WMGEP&MSGLIQMWXV]ERH1SPIGYPEV7XVYGXYVIERH[MXL4VSJIWWSV 8IR*IM^M-QTIVMEP'SPPIKI0SRHSR Publications -UFEP1)WWIR7'<MES,&VSSOIW71&VS[R-,ERH 1G'EYPI].; Selection of variant viruses during replication and transmission of H7N1 viruses in chickens and turkeys. Virology 433 8LqFEYH+'LEH®YJ.1SVIPPM1.1G'EYPI].;ERH,E]HSR (8 The relationship between mutation frequency and replication strategy in positive-sense single-stranded RNA viruses. Proceedings of the Royal Society B: Biological Sciences 277 (A/Udorn/1/2012) (A/Brisbane/10/2007) *PYSVIWGIRGIHIXIGXMSRSJXLIMR¾YIR^EZMVYWLEIQEKKPYXMRMRSRZMVYWIWFYHHMRKJVSQGIPPW MRJIGXIH[MXLEZMVYWXLEXJSVQWPSRK½PEQIRXW%9HSVRERHSRI[LMGLHSIWRSX% Brisbane/10/2007). 46 MRC National Institute for Medical Research -UFEP1<MES,&EMPPMI+;EVV]%)WWIR7'0SRHX&&VSSOIW 71&VS[R-,ERH1G'EYPI].; ;MXLMRLSWXZEVMEXMSRSJEZMERMR¾YIR^EZMVYWIW Philosophical Transactions of the Royal Society B: Biological Sciences 364 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR INFECTIONS AND IMMUNITY Immunoregulation Anne O’Garra FRS, AAAS Fellow, EMBO member, FMedSci Regulation of the immune response in infectious disease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½RHMRKWMRLYQER8&[LIVI[IMHIRXM½IHEVSFYWXFPSSH XVERWGVMTXMSREPMRXIVJIVSRMRHYGMFPIWMKREXYVI[IEVIEHZERGMRKSYVGPMRMGEPWXYHMIWXS WXVIRKXLIRXLIHMEKRSWMWSJ8&ERHXLIQSRMXSVMRKSJHVYKXVIEXQIRX;ILEZIRS[ HIQSRWXVEXIHXLEXXLIFPSSHXVERWGVMTXMSREPWMKREXYVISJ8&MWWMKRM½GERXP]HMQMRMWLIH F]X[S[IIOWEJXIVXVIEXQIRXSJJIVMRKKVIEXTSXIRXMEPXSQSRMXSVXLIIJ½GEG]SJ GYVVIRXERHRI[HVYKW-REHHMXMSRFEWIHSRSYV½RHMRKWMRLYQER8&[IEVI MRZIWXMKEXMRKXLI8]TI--*2WERH8]TI--*2MRHYGMFPIKIRIWYWMRKQSPIGYPEVQIXLSHW ERHMQTVSZIHQSYWIQSHIPWSJ8&XSMHIRXMJ]MQQYRIQIGLERMWQWSJTVSXIGXMSR SVTEXLSKIRIWMWMQTSVXERXJSVHMWIEWIGSRXVSPMRXYFIVGYPSWMWERHSXLIVFEGXIVMEP MRJIGXMSRW Publications &PSSQ'-+VELEQ'1&IVV]146;MPOMRWSR/%3RM 86S^EOIEW*<Y>6SWWIPPS9VKIPP.'LEYWWEFIP( &ERGLIVIEY.4EWGYEP:0MTQER1;MPOMRWSR6.ERH 3´+EVVE% Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLOS ONE 7:e46191 &IVV]146+VELEQ'11G2EF*;<Y>&PSGL7%% 3RM8;MPOMRWSR/%&ERGLIVIEY67OMRRIV.;MPOMRWSR 6.5YMRR'&PEROIRWLMT((LE[ER6'YWL..1INMEW% 6EQMPS3/SR314EWGYEP:&ERGLIVIEY.'LEYWWEFIP( ERH3´+EVVE% An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466 7EVEMZE1ERH3´+EVVE% The regulation of IL-10 production by immune cells. Nature Reviews Immunology 10 7IIVIJIVIRGIW ERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 47 INFECTIONS AND IMMUNITY Molecular Immunology Venizelos Papayannopoulos Mechanisms of neutrophil-mediated immune defense 0EFQIQFIVW2SVE&VER^O6]ER*MWLIV1EVMERRE-SERRSY.SEGLMQ/YVXL%RRMOE;EVREXWGL 1YPXMGIPPYPEVSVKERMWQWIZSPZIHWSTLMWXMGEXIHMQQYRIW]WXIQWXS TVSXIGXXLIQWIPZIWEKEMRWXMRJIGXMSR2IYXVSTLMPWEVIEQSRKWXXLI ½VWXMQQYRIGIPPWXSFIVIGVYMXIHXSWMXIWSJMRJIGXMSRERHTPE] GIRXVEPQMGVSFMGMHEPERHVIKYPEXSV]VSPIWHYVMRKMRJIGXMSR8LI]IRKYPJ ERHOMPPQMGVSFIWMRXVEGIPPYPEVP]ERHVIPIEWIERXMQMGVSFMEPJEGXSVWXLEX GSQFEXTEXLSKIRWI\XVEGIPPYPEVP]XLVSYKLHIKVERYPEXMSRERHXLI VIPIEWISJRIYXVSTLMPI\XVEGIPPYPEVXVETW2)8W2)8WEVI[IFPMOI WXVYGXYVIWGSQTSWIHSJHIGSRHIRWIHGLVSQEXMRERHERXMQMGVSFMEP TVSXIMRWXLEXXVETERHOMPPFEGXIVMEJYRKMZMVYWIWERHTEVEWMXIW;LMPI MQTSVXERXJSVMQQYRIHIJIRWI2)8SZIVEFYRHERGILEWFIIR MQTPMGEXIHMRMR¾EQQEXSV]ERHEYXSMQQYRIHMWIEWI;IEVIXV]MRK XSYRHIVWXERHLS[RIYXVSTLMPWVIKYPEXI2)8VIPIEWIERHLS[2)8W EJJIGXMQQYRIHIJIRGIMR¾EQQEXMSRERHHMWIEWI 2IYXVSTLMPWVIPIEWI2)8WXLVSYKLERSZIPGIPPHIEXLQIGLERMWQ MRZSPZMRKWSQIJEWGMREXMRKGIPPFMSPSK]XLIRYGPIEVIRZIPSTI HMWEWWIQFPIWERHXLIGLVSQEXMRHIGSRHIRWIWQM\MRK[MXLRIYXVSTLMPERXMQMGVSFMEPJEGXSVW[LMPIXLIGIPPVIQEMRWMRXEGX%XXLI QSPIGYPEVPIZIPVIEGXMZIS\]KIRWTIGMIWXVMKKIVXLIWIPIGXMZIXVERWPSGEXMSRSJERIYXVSTLMPWTIGM½GTVSXIEWIRIYXVSTLMPIPEWXEWI XSXLIRYGPIYW[LIVILMWXSRIWEVITEVXMEPP]GPIEZIHXSTVSQSXIGLVSQEXMRHIGSRHIRWEXMSR;IEVIWXYH]MRKXLIQIGLERMWQ SJRIYXVSTLMPIPEWXEWIXVERWPSGEXMSRERH[IEVITEVXMGYPEVP]MRXIVIWXIHMRLS[VIEGXMZIS\]KIRWTIGMIWERHSXLIVTEXL[E]WEVI VIKYPEXMRKXLMWTVSGIWW;IEVIEPWSXV]MRKXSYRHIVWXERHXLIREXYVISJXLIYTWXVIEQWMKREPWKSZIVRMRKRIYXVSTLMPEGXMZEXMSRERH XLIMRXIVTPE][MXLSXLIVMQQYRIGIPPWHYVMRKMRJIGXMSRERHXLIVIWSPYXMSRSJMR¾EQQEXMSR Publications 1IX^PIV/(*YGLW8%2EYWIIJ;16IYQEY\(6SIWPIV .7GLYP^I-;ELR:4ETE]ERRSTSYPSW:ERH>]GLPMRWO] % Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood 117 4ETE]ERRSTSYPSW:7XEEF(ERH>]GLPMRWO]% Neutrophil elastase enhances sputum solubilization in G]WXMG½FVSWMWTEXMIRXWVIGIMZMRK(2EWIXLIVET] PLOS ONE 6I 4ETE]ERRSTSYPSW:1IX^PIV/(,EOOMQ%ERH>]GLPMRWO] % Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. Journal of Cell Biology 191 Klebsiella pneumoniae trapped by NETs in the lung of an infected mouse. 48 MRC National Institute for Medical Research Neutrophils undergoing NET formation in response to Candida albicans. Neutrophil elastase (red) and myeloperoxidase (green) binding to decondensed chromatin (blue) prior to NET release. INFECTIONS AND IMMUNITY Immune Cell Biology Benedict Seddon Regulation of T cell homeostasis by antigen receptor signals and cytokines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in vivoERHQEXLIQEXMGEPQSHIPPMRKSJ P]QTLSTIRMEMRHYGIHTVSPMJIVEXMSR7MKRM½GERXP]XLIQSHIP[EWWYGGIWWJYPMRTVIHMGXMRK MRXIVGPSREPGSQTIXMXMSRFIX[IIR8GIPPWGSRWMWXIRX[MXLGSQTIXMXMSRJSVEGSQQSR VIWSYVGIVIUYMVIHJSVLSQISWXEXMGTVSPMJIVEXMSR3YVVIWYPXWWLS[XLEXHMZIVWIERH LIXIVSKIRISYWGPSREP8GIPPVIWTSRWIWGERFIEGGSYRXIHJSVF]EWMRKPIGSQQSR QSHIPSJLSQISWXEWMW A single stochastic divisions (SSD) model of cell cycle control in T cells. Lymphopenia induces T cells to undergo single divisions in a stochastic manner. Publications ,SKER87LYZEIZ%'SQQIRKIW(=EXIW%'EPPEVH68LMIFEYX67IHHSR& Clonally diverse T cell homeostasis is maintained by a common program of cell-cycle control. Journal of Immunology 190: 7MRGPEMV'7EMRM1ZERHIV0SIJJ-77EOEKYGLM7ERH7IHHSR& The long-term survival potential of mature T lymphocytes is programmed during development in the thymus. Science Signaling 4VE =EXIW%7EMRM11EXLMSX%ERH7IHHSR& Mathematical modeling reveals the biological program regulating lymphopenia-induced proliferation. Journal of Immunology 180 Modelled (A) and observed (B) population growth for two T cell clones (OT-I and F5) when they are proliferating either separately (solid lines) or together (dashed lines). 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 49 INFECTIONS AND IMMUNITY Molecular Immunology Gitta Stockinger EMBO member, FMedSci Development, maintenance and regulation of peripheral T cell compartments and immune responses 0EFQIQFIVW,IPIRE%LPJSVW.YHMX&MVS4ESPE(M1IKPMS.SES(YEVXI1ERSPMW+MEPMXEOMW/IMNM,MVSXE=MRK0M,IMOI1YIPPIV1EXXIS:MPPE 3YVJSGYWMWSRXLIHIZIPSTQIRXERHJYRGXMSRSJMRREXI ERHEHETXMZIG]XSOMRITVSHYGMRK8GIPPWERHMRREXI P]QTLSMHGIPPW8LGIPPWERH-0TVSHYGMRK-0' ERHQSHYPEXMSRSJIJJIGXSVJYRGXMSRWF]I\SKIRSYW ERHIRHSKIRSYWIRZMVSRQIRXEPJEGXSVW8LGIPPWEVI MQTSVXERXJSVLSWXHIJIRGIEKEMRWXJYRKEPTEXLSKIRWERH EVIGEYWEPP]MRZSPZIHMREYXSMQQYRIHMWIEWIW[LIVIEW -0'TPE]MQTSVXERXVSPIWMRPYRKMR¾EQQEXMSR ;IHIZIPSTIHJEXIVITSVXIVQSHIPWJSVXLIG]XSOMRIW -0ERH-0XSWXYH]HIZIPSTQIRXSJG]XSOMRI TVSHYGMRKGIPPWERHXLIMVFILEZMSVHYVMRKMRJIGXMSRin vivo Fate reporters make detection independent of current G]XSOMRITVSHYGXMSRERHVIZIEPI\XIRWMZITPEWXMGMX]MR XLIMQQYRIW]WXIQ*YVXLIVQSVIMRXLIGSRXI\XSJ ER)6'JYRHIHTVSKVEQ[IWXYH]XLIVSPISJXLIEV]P L]HVSGEVFSRVIGITXSV%L6MRXLIMQQYRIW]WXIQXV]MRK XSYRVEZIPMXWMQTEGXSRXLIJYRGXMSRSJHMJJIVIRXMQQYRI GIPPWMRXLIHIJIRGIEKEMRWXTEXLSKIRWERHMRMR¾EQQEXSV] HMWIEWIWWYGLEWTWSVMEWMWXLEXEVIMR¾YIRGIHF]KIRIXMGEW [IPPEWIRZMVSRQIRXEPJEGXSVW Publications ,MVSXE/(YEVXI.,:IPHLSIR1,SVRWF])0M='YE(. %LPJSVW,;MPLIPQ'8SPEMRM11IR^IP9+EVIJEPEOM% 4SXSGRMO%.ERH7XSGOMRKIV& *EXIQETTMRKSJ-0TVSHYGMRK8GIPPWMRMR¾EQQEXSV] responses. Nature Immunology 12 ;MPLIPQ',MVSXE/7XMIKPMX^&:ER7RMGO.8SPEMRM10ELP/ 7TEV[EWWIV8,IPQF],ERH7XSGOMRKIV& An IL-9 fate reporter demonstrates the induction of an MRREXI-0VIWTSRWIMRPYRKMR¾EQQEXMSR Nature Immunology 12 :IPHLSIR1,MVSXE/;IWXIRHSVJ%1&YIV.(YQSYXMIV0 6IREYPH.'ERH7XSGOMRKIV& The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 50 MRC National Institute for Medical Research -15XVIEXIH%L6HI½GMIRX mice develop heightened psoriasis-like skin MR¾EQQEXMSR A) Histological skin sections of AhR +/- and Ahr -/- B6 mice treated with imiquimod (IMQ) for 5 days. &5YERXM½GEXMSRSJ epidermal and scale (Stratum Corneum) thickness during IMQ treatment. INFECTIONS AND IMMUNITY Virology Jonathan Stoye Retrovirus-host interactions 0EFQIQFIVW7EQ*VEWIV;MPWSR0M7EHE]YOM3OYVE1EVXLE7ER^6EQSW4EYPE3VHSRI^7YEVI^1IPZ]R=ET+ISVKI=SYRK 'SQTEVEXMZIKIRSQIEREP]WMWWYKKIWXWXLEXZIVXIFVEXIWERH VIXVSZMVYWIWLEZIFIIRMRGSR¾MGXJSVXIRWSJQMPPMSRWSJ]IEVW-X MWXLYWYRWYVTVMWMRKXLEXEHIKVIISJGSIZSPYXMSRLEWXEOIRTPEGI VIWYPXMRKMRXLIHIZIPSTQIRXSJWTIGM½GHIJIRGIQIGLERMWQW by the host and of means to overcome such defences by the ZMVYW9RHIVWXERHMRKWYGLREXYVEPERXMZMVEPKIRIWQMKLXWYKKIWX RSZIPQIERWSJGSQFEXMRKVIXVSZMVEPMRJIGXMSR;IERXMGMTEXIXLEX XLIWIWXYHMIW[MPPWLIHRI[PMKLXSRXLIIEVP]WXEKIWSJVIXVSZMVYW VITPMGEXMSRERHXLIGSRXVSPSJGVSWWWTIGMIWMRJIGXMSR 6IWXVMGXMSRJEGXSVWJVSQHMJJIVIRXWTIGMIWEVIGETEFPISJVIGSKRMWMRK HMJJIVIRXVIXVSZMVYWIWMREWTIGM½GQERRIVETTEVIRXP]MRZSPZMRK QYPXMTPIPS[EJ½RMX]MRXIVEGXMSRW,S[IZIVJEGXSVWGSRXVSPPMRK WTIGM½GMX]EVITSSVP]YRHIVWXSSH;IEVIYWMRKEGSQFMREXMSRSJ WXVYGXYVEPKIRIXMGERHFMSGLIQMGEPETTVSEGLIWMRSYVEXXIQTXWXS YRHIVWXERHXLITVSGIWWSJZMVYWVIGSKRMXMSRF]JEGXSVWWYGLEW*Z and Trim5_6IGIRXTVSKVIWWMRGPYHIWXLIHIZIPSTQIRXSJERin vitro FMRHMRKEWWE]YWMRKTSP]QIVMWIHGETWMHERHXLIHIQSRWXVEXMSRXLEX EPPXLII\TSWIHWYVJEGISJXLIZMVEPGSVIGSRXVMFYXIWXSXLIFMRHMRK VIEGXMSR Publications 7XS]I.4 Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nature Reviews Microbiology 10 ,MPHMXGL01EXEHIIR6+SPHWXSRI('6SWIRXLEP4&8E]PSV -%ERH7XS]I.4 Ordered assembly of murine leukemia virus capsid protein SRPMTMHRERSXYFIWHMVIGXWWTIGM½GFMRHMRKF]XLIVIWXVMGXMSR factor, Fv1. Proceedings of the National Academy of Sciences of the United States of America 108¯ 3LOYVE7+SPHWXSRI('=ET1;,SPHIR(]I/8E]PSV-% ERH7XS]I.4 Novel escape mutants suggest an extensive TRIM5_ binding site spanning the entire outer surface of the murine leukemia virus capsid protein. PLoS Pathogens 7I 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR The retroviral core comprises hexameric arrays of capsid proteins. 7IPIGXMSRSJIWGETIQYXERXWJVSQVIWXVMGXMSREPPS[WXLIMHIRXM½GEXMSR of amino acids (red, acidic; green, basic) involved in virus recognition. MRC National Institute for Medical Research 51 INFECTIONS AND IMMUNITY Immune Cell Biology Pavel Tolar Activation of immune receptors 0EFQIQFIVW%RXSRMS'EWEP6SFIVX,SSKIFSSQ.EWSR0II)PM^EFIXL2EXOERWOM'EVPE2S[SWEH&LEOXM1MWXV] %RXMFSHMIWEVIGVMXMGEPJSVLYQERMQQYRMX]ERHXLIMV MRHYGXMSRLEWFIIRMRWXVYQIRXEPJSVXLIWYGGIWWSJQER] ZEGGMRIW,S[IZIVWSQISJXLIQSWXHERKIVSYWTEXLSKIRW SJXSHE]´W[SVPHWYGLEW,-:MR¾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nternalisation of a single antigen cluster (red) from presenting membranes is mediated by B cell’s invagination of the membranes (green). Publications 8SPEV4 Inside the microcluster: antigen receptor signalling viewed with molecular imaging tools. Immunology 133 8SPEV4ERH4MIVGI7/ A conformation-induced oligomerization model for B cell receptor microclustering and signaling. Current Topics in Microbiology and Immunology 340 8SPEV4,ERRE./VYIKIV4(ERH4MIVGI7/ The constant region of the membrane immunoglobulin mediates B cell-receptor clustering and signaling in response to membrane antigens. Immunity 30 52 MRC National Institute for Medical Research %&GIPPFPYII\XVEGXMRKERXMKIRKVIIRJVSQTYVM½IHTPEWQEQIQFVERIW (top), but not from a control membrane (bottom). Membranes were labelled with DiI (red). INFECTIONS AND IMMUNITY Immune Cell Biology Victor Tybulewicz EMBO member, FMedSci Signal transduction in B and T cells 0EFQIQFIVW(SVSXE%FYGI[MG^.SGLIR%GOIVQERR8MEKS&VE^ES2EXEPME(MRMWGLMSXY/EXLV]R*SYRXEMR,EVEPH,EVX[IKIVRob IVX/}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ouse models of Down syndrome 8VMWSQ]SJLYQERGLVSQSWSQI,WESGGYVWMREVSYRHMRPMZIFMVXLW ERHXLIVIWYPXMRKKIRIHSWEKIMQFEPERGIKMZIWVMWIXS(S[RW]RHVSQIXLIQSWX GSQQSRJSVQSJQIRXEPVIXEVHEXMSR-RGSPPEFSVEXMSR[MXL4VSJ)*MWLIV9'0[I EVIMRXIVIWXIHMRMHIRXMJ]MRKKIRIWSRXLMWGLVSQSWSQI[LMGL[LIRTVIWIRXMRXLVII GSTMIWGEYWIXLIQER]HMJJIVIRXTLIRSX]TIWSJ(S[RW]RHVSQI;ILEZIGVIEXIH ERSZIPQSYWIWXVEMRGEVV]MRKEJVIIP]WIKVIKEXMRKGST]SJ,WE[LMGLHMWTPE]W QER]SJXLIJIEXYVIWSJ(S[RW]RHVSQIMRGPYHMRKPIEVRMRKHMJ½GYPXMIWERHGEVHMEG EFRSVQEPMXMIW;IEVIQETTMRKXLIPSGEXMSRSJHSWEKIWIRWMXMZIKIRIWXLEXGEYWI (S[RW]RHVSQITLIRSX]TIWYWMRKGLVSQSWSQIIRKMRIIVMRKXIGLRMUYIW Signals from the BAFF receptor (BAFFR) controlling B cell homeostasis are transduced via the B cell antigen receptor (BCR) and the Syk tyrosine kinase. Publications 7GL[IMKLSJJIV):ERIW02]W.'ERXVIPP(1G0IEV]77QMXLIVW2ERH8]FYPI[MG^:0. The B cell antigen receptor transduces signals from the BAFF receptor required for cell survival. Immunity, 38 /WMSRHE37EZIPMIZ%/SGLP66ETPI].*EVSYHM17QMXL+EVZMR.);YP½RK'6MXXMRKIV/'EVXIV8ERH 8]FYPI[MG^:0. Mechanism and function of Vav1 localization in TCR signaling. Journal of Cell Science 125 6I]RSPHW0);EXWSR%6&EOIV1.SRIW8%(´%QMGS+6SFMRWSR7(.SJJVI'+EVVMHS9VFERM76SHVMKYI^ 1ER^ERIUYI.'1EVXMRS)GLEVVM)%YVVERH0MSRW17LIIV((EKRE&VMGEVIPPM*2M^IXMG(1G'EFI'.8YVRIPP %7/IVQSVKERX7-QLSJ&%%HEQW6*MWLIV)1'8]FYPI[MG^:0.,EVX-6ERH,SHMZEPE(MPOI/1 Tumour angiogenesis is reduced in the Tc1 mouse model of Down’s syndrome. Nature 465 Chromosome engineering to create duplications and deletions of megabase regions of mouse chromosomes to model Down syndrome. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR MRC National Institute for Medical Research 53 INFECTIONS AND IMMUNITY Immunoregulation Andreas Wack -QQYRIVIWTSRWIXSMR¾YIR^E 0EFQIQFIVW7XIJERME'VSXXE7STLME(EZMHWSR+VIKSV])PPMW%RRMXE+NSOE8IVIWE1G'EFI 7IEWSREPMR¾YIR^EVITVIWIRXWEGSRWXERXFYVHIRXSTYFPMGLIEPXLERH MR¾YIR^ETERHIQMGWHYIXSRI[ZMVYWWXVEMRWTSWIEWIVMSYWKPSFEPXLVIEX 8LIMR¾YIR^EZMVYWGEYWIWHEQEKIXSXLIMRJIGXIHPYRKXMWWYIERHMRHYGIW ERMQQYRIVIWTSRWIXLEXMWRIGIWWEV]XSIPMQMREXIXLIZMVYWFYXEXXLI WEQIXMQIGSRXVMFYXIWXSPYRKTEXLSPSK]-R¾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¾YIR^EERHXLIMVMQTEGXSRXLISYXGSQISJMRJIGXMSREVIEPWS WXYHMIH*YVXLIVQSVI[IMRZIWXMKEXIXLIVSPIWSJREXYVEPOMPPIVGIPPWERH KVERYPSG]XIWMRMR¾YIR^EMRJIGXMSRERHGSMRJIGXMSR8LIWIWXYHMIWEPPS[ YWXSPMROIEVP]IZIRXWMRMRJIGXMSRXSWYFWIUYIRXMQQYRIQIHMEXIH TEXLSPSK]SVTVSXIGXMSR Publications 'EPEFVS78SVXSPM1&EYHRIV&'4EGMXXS%'SVXIWI1 3´,EKER(8(I+VIKSVMS)7IYFIVX%ERH;EGO% Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 29 7IYFIVX%'EPEFVS77ERXMRM0+EPPM&+IRSZIWI%:EPIRXMRM 7%TVIE7'SPETVMGS%(´3VS9+MYPMERM114EPPESVS1 4M^^E13´,EKER(8;EGO%6ETTYSPM6ERH(I+VIKSVMS ) Adjuvanticity of the oil-in-water emulsion MF59 is MRHITIRHIRXSJ2PVTMR¾EQQEWSQIFYXVIUYMVIWXLI adaptor protein MyD88. Proceedings of the National Academy of Sciences of the United States of America 108 ;EGO%3TIRWLE[4ERH3´+EVVE% Contribution of cytokines to pathology and protection in virus infection. Current Opinion in Virology 1 8LIXVERWGVMTXMSREPVIWTSRWISJQSYWITVMQEV]EMV[E]ITMXLIPMEXSMR¾YIR^EZMVYW infection over time. We currently dissect the upstream events leading to this reproducible sequence of clusters of induced and suppressed genes. 54 MRC National Institute for Medical Research INFECTIONS AND IMMUNITY Mycobacterial Research Robert Wilkinson FRCP Understanding and intervening in HIV-associated tuberculosis 0EFQIQFIVW%RRE'SYWWIRW6EGLIP0EM%HVMER1EVXMRIEY/EXEPMR;MPOMRWSR 8LITVSKVEQQIHIVMZIWMXWVIWIEVGLUYIWXMSRWJVSQXLIGPMRMGEPGEVISJXYFIVGYPSWMW 8&ERH,-:8&GSMRJIGXIHTIVWSRWMR7SYXL%JVMGEERH0SRHSR8LVSYKLGPMRMGEPP] FEWIHWXYHMIW[IEMQXSMQTVSZIORS[PIHKISJTEXLSKIRIWMWERHXLIVIF]MQTVSZI TVIZIRXMSRERHXVIEXQIRX ;IGSRXVMFYXIHXSXLIHIWGVMTXMSRSJEHMWXMRGXXVERWGVMTXSQMGWMKREXYVISJEGXMZI8& ERHEVIGSRHYGXMRKJYVXLIVWXYHMIWI\XIRHMRKXSXLIWXYH]SJXYFIVGYPSWMWXVIEXQIRX QSRMXSVMRK;ILEZIHIXIVQMRIHXLEXZMXEQMR(HI½GMIRG]MWLMKLP]TVIZEPIRXMR 'ETI8S[REWWSGMEXMRK[MXLWYWGITXMFMPMX]XSXYFIVGYPSWMWFSXLMRFSXL,-:MRJIGXIH ERHYRMRJIGXIHTIVWSRW;LIRYWIHEWEREHNYRGXXSXLIXVIEXQIRXSJXYFIVGYPSWMW ZMXEQMR(WYTTVIWWIWTVSMR¾EQQEXSV]G]XSOMRIVIWTSRWIWERHEXXIRYEXIWXLI WYTTVIWWMZIIJJIGXSJERXMQMGVSFMEPXLIVET]SRWIGVIXMSRSJ-0''0ERH-*2_ 8LMWHIQSRWXVEXIWETVIZMSYWP]YRETTVIGMEXIHVSPIJSVZMXEQMR(WYTTPIQIRXEXMSRMR EGGIPIVEXMRKVIWSPYXMSRSJMR¾EQQEXSV]VIWTSRWIW Publications Fluorescence microscopy of MTB-HIV co-infected macrophages stained for polycaspase activity (green punctate and circular staining) a cellular nuclei (blue). The caspase stain also stains the outer cell wall of MTB and these can be seen as small green rods. Untreated cells (A) have a lot less punctate circular green staining and a lot more MTB compared to cells treated with 100nM 25-hydroxy vitamin D suggesting it induces apoptosis and inhibits MTB growth. 'SYWWIRW%/;MPOMRWSR6.,ERMJE=2MOSPE]IZWO]]:)POMRKXSR 48-WPEQ/8MQQW41:IRXSR86&SXLEQPI]+,4EGOI+) (EVQEPMRKEQ1(EZMHWSR621MPFYVR,.&EOIV0:&EVOIV6( 1IMR'%&LE[6SWYR02YEQEL6=SYRK(&(VSFRMI[WOM *%+VMJ½XLW'.ERH1EVXMRIEY%6 :MXEQMR(EGGIPIVEXIWVIWSPYXMSRSJMR¾EQQEXSV]VIWTSRWIW during tuberculosis treatment. Proceedings of the National Academy of Sciences of the United States of America 109 1EVXMRIEY%62LEQS]IFSRHI73RM86ERKEOE1<1EVEMW7 &ERKERM28WIOIPE6&EWLI0HI%^IZIHS:'EPH[IPP.:IRXSR 868MQQW41;MPOMRWSR/%ERH;MPOMRWSR6. Reciprocal seasonal variation in vitamin D status and XYFIVGYPSWMWRSXM½GEXMSRWMR'ETI8S[R7SYXL%JVMGE Proceedings of the National Academy of Sciences 1058 &IVV]146+VELEQ'11G2EF*;<Y>&PSGL7%%3RM8 ;MPOMRWSR/%&ERGLIVIEY67OMRRIV.;MPOMRWSR6.5YMRR' &PEROIRWLMT((LE[ER6'YWL..1INMEW%6EQMPS3/SR31 4EWGYEP:&ERGLIVIEY.'LEYWWEFIP(ERH3´+EVVE% An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466 Three dimensional network principal component analysis (PCA) plot showing the effect of intensive-phase antituberculous therapy on the circulating immune response in patients with smear-positive pulmonary tuberculosis. Individual points represent a single analyte. Lines link analytes to the analyte which has the most similar pattern of change during the course of treatment. Analytes are colored by R2-statistic: blue represents a decrease, and yellow an increase, with time of treatment. 7IIVIJIVIRGIW ERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRW JVSQXLMWKVSYTMR MRC National Institute for Medical Research 55 INFECTIONS AND IMMUNITY Molecular Immunology Mark Wilson 6IKYPEXMSRSJ8LGIPPWHYVMRKEPPIVKMGMR¾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½IHQSPIGYPEVTEXL[E]WVIWTSRWMFPIJSV8LGIPPHIZIPSTQIRXERH IJJIGXSVJYRGXMSR+IRIERH62%QERMTYPEXMSRXIGLRMUYIWLEZIMHIRXM½IH ERIX[SVOSJQM62%WERHEOMREWIHITIRHIRXGEWGEHI[LMGLVIKYPEXI 8LJYRGXMSRERHX]TIMQQYRMX] De novoMQQYRIVIWTSRWIWHIZIPST EPSRKWMHISRKSMRKMQQYRIVIWTSRWIW-RGSPPEFSVEXMSR[MXL2-16 MRZIWXMKEXSVW[ILEZIMHIRXM½IHXLEX8LGIPPWGSRXVMFYXIXSWIGSRHEV] MQQYRMX]XLVSYKLVITVSKVEQQMRKQIGLERMWQW;IEVIEPWSMRZIWXMKEXMRK LS[8LGIPPWGLERKIXLVSYKLSYXMRJIGXMSRSVEPPIVK]ERHHYVMRKVETMH MQQYRMX]8LIWIWXYHMIW[MPPLIPTJEGMPMXEXILIPQMRXLIPMQMREXMSRWXVEXIKMIW ERHMHIRXMJ]RSZIPMRXIVZIRXMSRWJSVEPPIVKMGHMWIEWI Immunity is costly. -QQYRSPSKMGEPP]VIWMWXERXQMGIHIZIPSTWMKRM½GERXMQQYRSTEXLSPSK] following expulsion of the intestinal helminth Heligmosomoides polygyrus. Publications 3OS]I-7ERH;MPWSR17 CD4+ T helper 2 cells - microbial triggers, differentiation requirements and effector functions. Immunology 134 ;MPWSR17'LIIZIV%;;LMXI7(8LSQTWSR6;ERH;]RR8% IL-10 blocks the development of resistance to re-infection with Schistosoma mansoni. PLoS Pathogens 7I ;MPWSR176EQEPMRKEQ866MZSPPMIV%7LIRHIVSZ/1IRXMRO/ERI111EHEPE 7/'LIIZIV%;%VXMW(/IPWEPP&0ERH;]RR8% 'SPMXMWERHMRXIWXMREPMR¾EQQEXMSRMR-0QMGIVIWYPXWJVSQ-06_2mediated attenuation of IL-13 activity. Gastroenterology 140 56 MRC National Institute for Medical Research miRNA-mediated regulation. Using genomewide analysis at the tissue (A) and cellular level (B, Th cell differentiation pathways, and C, Th2 cell), we are investigating the molecular mechanisms of Th2 immunity and immunopathology following infection. INFECTIONS AND IMMUNITY INFECTIONS AND IMMUNITY Immune Cell Biology Mycobacterial Research Douglas Young FMedSci Victor Tybulewicz Mycobacterial pathogenesis: gene expression and innate immune response 0EFQIQFIVW/VMWXMRI%VRZMK6SKIV&Y\XSR7XITLIR'SEHI8IVIWE'SVXIW.SERRE,SYKLXSR(IFSVEL,YRX 'LVMWXMRE/ELVEQERSKPSY%RKIPE6SHKIVW+VELEQ6SWI=M;ERK1MR=ERK 3RIXLMVHSJXLIKPSFEPTSTYPEXMSRMWI\TSWIHXSMRJIGXMSR[MXL Mycobacterium tuberculosisFYXSRP]XIRTIVGIRXSJMRHMZMHYEPW [MPPHIZIPSTXYFIVGYPSWMW8LISYXGSQISJMRJIGXMSRHITIRHWSR EGSQTPI\WIVMIWSJMRXIVEGXMSRW[MXLXLIMQQYRIW]WXIQ[LMGL GERVIWYPXMRHMWIEWISVMRETIVWMWXIRXEW]QTXSQEXMGPEXIRX MRJIGXMSR;IEVIWXYH]MRKXLI[E]XLEXM. tuberculosis evades LSWXMQQYRMX]F]QMWHMVIGXMRKMRREXIMQQYRIVIGSKRMXMSRERHF] EHETXMRKXSEJSVQXLEXVIWMWXWOMPPMRKF]TLEKSG]XIW9PXMQEXIP][I EMQXSHIZIPSTHVYKWXLEXVETMHP]IPMQMREXITIVWMWXMRKFEGXIVMEERH ZEGGMRIWXLEXIPMGMXQSVIIJJIGXMZIMQQYRMX] ;IEVIYWMRKLMKLXLVSYKLTYXWIUYIRGMRKXIGLRSPSKMIWXS HI½RIXLIKIRIXMGHMZIVWMX]SJM. tuberculosis ERHXSWXYH]KIRI VIKYPEXMSREXXVERWGVMTXMSREPERHTSWXXVERWGVMTXMSREPPIZIPW;I LEZIHMWGSZIVIHERI\XIRWMZIVITIVXSMVISJRSRGSHMRK62%W ERHEVII\TPSVMRKXLIMVJYRGXMSRMRTEVXXLVSYKLTEVXMGMTEXMSR MR7]WXI18FE)YVSTIERGSRWSVXMYQYWMRKEW]WXIQWFMSPSK] ETTVSEGLXSGLEVEGXIVMWIXLIJYRHEQIRXEPFMSPSK]SJ8&3YV [SVOHIQSRWXVEXIWXLEXKIRIXMGZEVMEXMSREQSRKWXGPMRMGEPMWSPEXIW of M. tuberculosisVIWYPXWMRTLIRSX]TMGHMJJIVIRGIWMRXLIMV MRXIVEGXMSR[MXLXLILSWXMRREXIMQQYRIW]WXIQ;ITVSTSWIXLEX HMJJIVIRGIWMRMRREXIMQQYRIVIGSKRMXMSRHVMZIXLIITMHIQMSPSK] SJXLMWGSQTPI\HMWIEWI Mapping of transcriptional start sites by RNAseq. The gene encoding sigma factor E has three start sites, there is preferential transcription of a leaderless mRNA in stationary phase. Publications %VRZMK/&'SQEW-8LSQWSR26,SYKLXSR.&SWLSJJ,-'VSYGLIV2.6SWI+4IVOMRW88 4EVOLMPP.(SYKER+ERH=SYRK(& Sequence-based analysis uncovers an abundance of non-coding RNA in the total transcriptome of Mycobacterium tuberculosis. PLoS Pathogens 7I 4SVXIZMR(+EKRIY\7'SQEW-ERH=SYRK( Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages. PLoS pathogens 7I %VRZMK/&ERH=SYRK(& -HIRXM½GEXMSRSJWQEPP62%WMRMycobacterium tuberculosis. Molecular Microbiology 73 FISH image of a tuberculosis bacterium expressing small RNA MTS1338. 7IIVIJIVIRGIWERHMRXLI FMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 57 INFECTIONS AND IMMUNITY Virology WHO Collaborating Centre for 6IJIVIRGIERH6IWIEVGLSR-R¾YIR^E;-' Director: John McCauley 0EFQIQFIVW6SH(ERMIPW(ITYX](MVIGXSV=MTY0MR%WWMWXERX(MVIGXSV2MGO'EXXPI/EVIR'VSWW:MGOM+VIKSV]'LERHVMOE ,EPEM0]RR;LMXXEOIV>LIRK<MERK 8LI;,3'SPPEFSVEXMRK'IRXVIJSV-R¾YIR^EMWSRISJWM\'SPPEFSVEXMRK'IRXVIWXLEXEPSRK[MXL;,32EXMSREP-R¾YIR^E 'IRXVIW2-'WMRGSYRXVMIWJSVQXLI;,3+PSFEP-R¾YIR^E7YVZIMPPERGIERH6IWTSRWI7]WXIQXSXVEGOMR¾YIR^EZMVYWIW EWXLI]GMVGYPEXIEVSYRHXLI[SVPH:MVYWIWEVIGLEVEGXIVMWIHERXMKIRMGEPP]ERHKIRIXMGEPP]ERHXLIMVVIWMWXERGIXSERXMZMVEPHVYKW MWHIXIVQMRIH6IWYPXWSJXLIWIEREP]WIWJVSQIEGLGSPPEFSVEXMRKGIRXVIEVIYWIHXSHIZIPSTVIGSQQIRHEXMSRWJSVXLIQSWX ETTVSTVMEXIWXVEMRWJSVYWIMRWIEWSREPMR¾YIR^EZEGGMRIWERHTVSZMHIEHZMGIXSREXMSREPEYXLSVMXMIWSRXLIKPSFEPERHVIKMSREP MR¾YIR^EGMVGYPEXMSR 6IWIEVGLLEWJSGYWIHSRVIGIRX,2ZMVYWIWXLEXWLS[EPXIVEXMSRWMRXLIMVEFMPMX]XSFMRHXSWMEPMGEGMHVIGITXSVW1ER],2 ZMVYWWXVEMRWEKKPYXMREXIVIHFPSSHGIPPWXLVSYKLXLIMVRIYVEQMRMHEWIKP]GSTVSXIMR[LMGLLEWQEVOIHMQTPMGEXMSRWJSVXLIERXMKIRMG EREP]WMWSJXLIWIZMVYWIW%PPSYVWXYHMIWEVIGEVVMIHSYX[MXLXLI2-'WJVSQEVSYRHXLI[SVPH[MXLSXLIV;,3'SPPEFSVEXMRK 'IRXVIWXLI9/,IEPXL4VSXIGXMSR%KIRG]XLI2EXMSREP-RWXMXYXIJSV&MSPSKMGEP7XERHEVHWERH'SRXVSPQIQFIVWSJXLI)YVSTIER 'SQQYRMX]2IX[SVOSJ6IJIVIRGI0EFSVEXSVMIWJSVLYQERMR¾YIR^EERHXLI;IPPGSQI8VYWX7ERKIV-RWXMXYXI Publications /PMQSZ%-+EVXIR66YWWIPP'&EVV-+&IWWIPEEV8+ (ERMIPW6)RKIPLEVHX3++VSLQERR+-XEQYVE7/IPWS %1G'EYPI].3HEKMVM87QMXL(8EWLMVS1<Y<;IFF] 6;ERK(=I>=YIPSRK7>LERK;ERH'S\2 WHO recommendations for the viruses to be used MRXLI7SYXLIVR,IQMWTLIVI-R¾YIR^E:EGGMRI epidemiology, antigenic and genetic characteristics of MR¾YIR^E%,2THQ%,2ERH&MR¾YIR^E viruses collected from February to September 2011. Vaccine 30 &EVV-+1G'EYPI].'S\2(ERMIPW6)RKIPLEVHX3+ *YOYHE/+VSLQERR+,E]%/IPWS%/PMQSZ%3HEKMVM 87QMXL(6YWWIPP'8EWLMVS1;IFF]6;SSH.=I> ERH>LERK; Epidemiological, antigenic and genetic characteristics of WIEWSREPMR¾YIR^E%,2%,2ERH&MR¾YIR^E viruses: basis for the WHO recommendation on the GSQTSWMXMSRSJMR¾YIR^EZEGGMRIWJSVYWIMRXLI 2010 Northern Hemisphere season. Vaccine 28 0MR=4+VIKSV]:'SPPMRW4/PSIWW.;LEVXSR7'EXXPI2 0EGOIRF]%(ERMIPW6ERH,E]% Neuraminidase receptor binding variants of human MR¾YIR^E%,2ZMVYWIWHYIXSWYFWXMXYXMSRSJEWTEVXMG acid 151 in the catalytic site - role in virus attachment? Journal of Virology 84 %QMRSEGMHWYFWXMXYXMSRWMRXLIMR¾YIR^E& virus haemagglutinin B/Yamagata lineage clades 2 (red) and 3 (green). The amino acid changed on adaptation to eggs is shown in pink. 58 MRC National Institute for Medical Research Phylogenetic analysis of the HA gene of MR¾YIR^E&=EQEKEXEPMRIEKIZMVYWIW%QMRSEGMH WYFWXMXYXMSRWXLEXHI½RIKIRIXMGRSHIWEVIWLS[R 7IIVIJIVIRGIWERHMRXLI FMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR Structural Biology Mathematical Biology Willie Taylor (Head of Division) Richard Goldstein Molecular Structure Steve Gamblin (Joint Head of Division) Steve Smerdon (Joint Head of Division) Paul Driscoll Annalisa Pastore Andres Ramos Katrin Rittinger Ian Taylor Physical Biochemistry Justin Molloy (Head of Division) Tom Carter Ed Hulme John Offer Peter Rosenthal Martin Webb MRC National Institute for Medical Research 59 STRUCTURAL BIOLOGY Physical Biochemistry Tom Carter 7IGVIXSV]SVKERIPPIJSVQEXMSRXVEJ½GOMRKERHI\SG]XSWMW 0EFQIQFIVW-ERMRE'SRXI)QQE'SSOWSR%RE:MSPIXE*SRWIGE.IRRMJIV*VEQTXSR2MOSPEM/MWOMR0EYVE/RMTI 3RISJXLI[E]WMR[LMGLGIPPWWIRWIERHVIWTSRHXSXLIMVIRZMVSRQIRXMWXLVSYKL XLIGIPPWYVJEGII\TVIWWMSRSJMRXIKVEPQIQFVERITVSXIMRWIKLSVQSRIVIGITXSVW MSRGLERRIPWEHLIWMSRQSPIGYPIWIXGERHXLIWIGVIXMSRSJWSPYFPIQSPIGYPIWMRXSXLI I\XIVREPIRZMVSRQIRXIKLSVQSRIWXVERWQMXXIVWQSVTLSKIRW8LIGSVVIGXHIPMZIV] SJWYGLQSPIGYPIWXSXLIGIPPWYVJEGISVI\XVEGIPPYPEVWTEGIMRZSPZIWXLIWIGVIXSV] TEXL[E];IWXYH]XLIWIGVIXSV]TEXL[E]MRSVHIVXSYRHIVWXERHXLITVSGIWWIWXLEX YRHIVPMIXLIJSVQEXMSRXVEJ½GOMRKERHI\SG]XSWMWSJVIKYPEXIHWIGVIXSV]SVKERIPPIW 7+WXLITSWX+SPKMQIQFVERIFSYRHGSRXEMRIVWXLEXWXSVIERHHIPMZIVTVSXIMRWXS XLIGIPPWYVJEGII\XIVMSVMRVIWTSRWIXSI\XIVREPWMKREPW 3YVQSHIPW]WXIQMWXLIIRHSXLIPMEPGIPP)'ERHMXWVIKYPEXIH7+XLI;IMFIP 4EPEHIFSH];4&;4&I\SG]XSWMWYRHIVPMIWWIGVIXMSRSJELSWXSJGSEKYPERXERH MR¾EQQEXSV]QSPIGYPIWMQTSVXERXJSVLYQERLIEPXL*MKYVI3YVVIGIRX[SVO &MIVMRKWIXEPLEWWLS[RXLEX;4&I\SG]XSWMWMWGSRXVSPPIHF]XLIMRXIVTPE] FIX[IIRQYPXMTPIWSPYFPIFMRHMRKTEVXRIVW7PTE1]6-4SJXLI;4&6EFTVSXIMR 6EFE*MKYVI Figure 1. Endothelial cells line the lumen of all blood vessels and control vascular homeostasis through secretion of a variety of mediators from specialised secretory granules called Weibel-Palade bodies (WPBs). Publications &MIVMRKW6,IPPIR2/MWOMR2/RMTI0*SRWIGE%:4EXIP&1IPM%6SWI1,ERREL1.ERH'EVXIV8 The interplay between the Rab27A effectors Slp4 a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis. Blood 120 /RMTI01IPM%,I[PIXX0&MIVMRKW6(IQTWXIV.7OILIP4,ERREL1.ERH'EVXIV8 A revised model for the secretion of tPA and cytokines from cultured endothelial cells. Blood 116 &EFMGL:1IPM%/RMTI0(IQTWXIV.)7OILIP4,ERREL1.ERH'EVXIV8 Selective release of molecules from Weibel-Palade bodies during a lingering kiss. Blood 111 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRJVSQXLMWKVSYTMR 60 MRC National Institute for Medical Research Figure 2. WPBs recruit multiple Rab proteins, but exocytosis is controlled by the interplay of the soluble effectors Slp4-a and MyRIP on Rab27a. STRUCTURAL BIOLOGY Molecular Structure Paul Driscoll Structural and functional analysis of signalling proteins 0EFQIQFIVW(MIKS)WTSWMXS8LEVMRHY*IVRERHS%GIP]+EV^E+EVGME,ERW/SWW0MP]2IQEXSPPELM8MQSXL]6EKER'LVMWXMRI6MGLXIV +IQQE;MPHWQMXL6MGLEVH=MQ 2YGPIEVQEKRIXMGVIWSRERGI216WTIGXVSWGST]TVSZMHIWEZEPYEFPI QIERWXSTVSFIXLIXLVIIHMQIRWMSREPWXVYGXYVIH]REQMGWERHFMRHMRK TVSTIVXMIWSJFMSPSKMGEPQSPIGYPIWPEVKIERHWQEPP3YVKVSYTIQTPS]W WXEXISJXLIEVX216EPSRKWMHIFMSTL]WMGEPFMSGLIQMGEPERHGIPPFMSPSK] XIGLRMUYIWXSMRZIWXMKEXIXLIREXYVISJMRXIVEGXMSRWFIX[IIRTVSXIMRW MQTPMGEXIHMRJYRHEQIRXEPGIPPYPEVERHSVKERMWQEPTVSGIWWIW8LIWIMRGPYHI XLIEGXMZEXMSRSJHIEXLVIGITXSVWMKREPPMRKPMQFVIKIRIVEXMSRMRXLI EHYPXRI[XXLIVIKYPEXMSRSJTLSWTLSPMTEWI'MWS^]QIWERHXLIVSPISJ `KP]GSTVSXIMRMRERXMTLSWTLSPMTMHW]RHVSQI;IEPWSGSRXVMFYXIXS VIWIEVGLXSMRZIWXMKEXIXLIMQTEGXSJMRXIVZIRXMSRWMRXSXLIHIZIPSTQIRX SJXLIQSHIPSVKERMWQDrosophila melanogaster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ifferential CD95-binding for wild type and mutant forms of FADD revealed by 2D heteronuclear NMR. Publications &YRRI]8( )WTSWMXS( 1EW(VSY\' 0EQFIV) &E\IRHEPI6; 1EVXMRW1 'SPI% 7ZIVKYR((VMWGSPP4'ERH/EXER1 Structural and functional integration of the PLCa interaction domains critical for regulatory mechanisms and signaling deregulation. Structure 20 'LIRK0=&EMPI]%40IIZIVW7.6EKER8.(VMWGSPP4'ERH+SYPH%4 Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell 146 CD95-dependent cell death in FADD-/- Jurkat cells reconstituted with a mutant CD95-dependent cell death in FADD-/- Jurkat cells reconstituted with a mutant form of FADD, monitored for activation of caspase-3 using FACS analysis. )WTSWMXS(7EROEV%1SVKRIV26SFMRWSR':6MXXMRKIV/ERH(VMWGSPP4' Solution NMR investigation of the CD95/FADD homotypic death domain complex suggests lack of engagement of the CD95 C terminus. Structure 18 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR MRC National Institute for Medical Research 61 STRUCTURAL BIOLOGY Molecular Structure Steve Gamblin FRS, EMBO member, FMedSci 7XVYGXYVEPFMSPSK]SJMR¾YIR^EIRIVK]QIXEFSPMWQERHGERGIV 0EFQIQFIVW4EXVMGO'SPPMRW4IXIV'SSQFW:EPIVME(I1EVGS'LYR.MRK2IMP.YWXMR1EXXLI[7ERHIVW.SLR7OILIP )PM^EFIXL9RHIV[SSH7IFEWXMIR:EGLMIVM&MRK<MES%PI\<MSRK We study the structure ERHJYRGXMSRSJQSPIGYPIW MRZSPZIHMRHMWIEWITVSGIWWIW WYGLEWMR¾YIR^EHMEFIXIW ERHGERGIV;IYWI<VE] GV]WXEPPSKVETL]ERH216 XSHIXIVQMRIXLIXLVII HMQIRWMSREPWXVYGXYVIW and dynamics of these QSPIGYPIW-RGSQFMREXMSR [MXLSXLIVFMSTL]WMGEP FMSGLIQMGEPERHFMSPSKMGEP XIGLRMUYIWXLIHEXELIPT YWIPYGMHEXIXLIJYRGXMSRSJ the proteins of interest and TVSZMHIMRJSVQEXMSRXLEXQE]FIYWIJYPJSVXLIHIZIPSTQIRXSJ XLIVETIYXMGETTVSEGLIW We are interested in the structure and function of the two QENSVWYVJEGIKP]GSTVSXIMRWSJMR¾YIR^EZMVYWLIQEKKPYXMRMR ERHRIYVEQMRMHEWI8LMW[SVOLEWFIIRGSRHYGXIHEWEPSRK WXERHMRKGSPPEFSVEXMSR[MXL.SLR7OILIPERHRS[EPWSMRZSPZIW .SLR1G'EYPI]´WKVSYTMR:MVSPSK]EW[IPPEWIWWIRXMEPGSRXEGXW [MXL2-16´W;-'%WTEVXSJXLMWIJJSVX[SVOMRK[MXL%RXSRMS 0ER^EZIGGLMEERHLMWGSPPIEKYIW[ILEZIJSYRHXLEXERERXMFSH] GEPPIH*-GERGSQFEXEPPMR¾YIR^E%ZMVYWIWXLEXGSQQSRP] GEYWIHMWIEWIMRLYQERWERHMRERMQEPW8LI½RHMRKVITVIWIRXWE TSXIRXMEPXYVRMRKTSMRXMRXLIHIZIPSTQIRXSJ¾YXVIEXQIRXWERH MRXMQIQE]LIPTXSTEZIXLI[E]JSVEYRMZIVWEP¾YZEGGMRI Ribbons representation of two orthogonal views of active AMPK. The kinase domain is coloured in yellow with its activation loop in pink. The regulatory gamma subunit which binds AMP/ADP/ATP competitively is coloured in red. Ribbons representation of the crystal structure of the crossreactive FI6 antibody binding to an HA trimer. Publications <MES&7ERHIVW1.9RHIV[SSH),IEXL61E]IV*:'EVQIRE(.MRK';EPOIV4%)GGPIWXSR.*,EMVI0*7EMY4,S[IPP7%%EWPERH61EVXMR76 'EVPMRK(ERH+EQFPMR7. Structure of mammalian AMPK and its regulation by ADP. Nature 472 'SVXM(:SWW.+EQFPMR7.'SHSRM+1EGEKRS%.EVVSWWE](:EGLMIVM7+4MRRE(1MRSPE%:ER^IXXE*7MPEGGM'*IVRERHI^6SHVMKYI^&1%KEXMG+ &MERGLM7+MEGGLIXXS7EWWIPPM-'EPHIV07EPPYWXS*'SPPMRW4,EMVI0*8IQTIVXSR20ERKIHMNO.417OILIP..ERH0ER^EZIGGLME% %RIYXVEPM^MRKERXMFSH]WIPIGXIHJVSQTPEWQEGIPPWXLEXFMRHWXSKVSYTERHKVSYTMR¾YIR^E%LIQEKKPYXMRMRW Science 333 1EVKYIVSR6.YWXMR23LRS/7LEVTI107SR.(VYV]---;.:SMKX41EVXMR768E]PSV;6(I1EVGS:4MVVSXXE:6IMRFIVK(ERH+EQFPMR7. Role of the polycomb protein EED in the propagation of repressive histone marks. Nature 461 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 62 MRC National Institute for Medical Research STRUCTURAL BIOLOGY Mathematical Biology Richard Goldstein Modelling the evolution of molecular components, systems, and behaviours 0EFQIQFIVW1EVXMR+SHER]/]VMEOSW/IRX^SKPEREOMW&LEZMR/LEXVM'LVMWXSTLIV1SRMX+VERX8LMPXKIR %PPFMSPSK]MWXLIVIWYPXSJIZSPYXMSR-RSVHIVXS YRHIVWXERHPMJI[IRIIHXSMRZIWXMKEXIXLIIZSPYXMSREV] TVSGIWWXLEXHIXIVQMRIWMXWJSVQERHJYRGXMSR&IGEYWI PMZMRKXLMRKWIRGSHIXLMWIZSPYXMSREV]LIVMXEKIWXYHMIWSJ XLIMVTVSTIVXMIWGERTVSZMHIMRWMKLXWMRXSXLIIZSPYXMSREV] TVSGIWW*SPPS[MRKXLIIZSPYXMSREV]TEXLSJWTIGM½G components can provide important information about XLIGLEVEGXIVMWXMGWSJPMZMRKSVKERMWQW'SQFMRMRKMRWMKLXW JVSQTL]WMGEPGLIQMWXV]GSRHIRWIHQEXXIVTL]WMGWEVXM½GMEP MRXIPPMKIRGIGSQTPI\MX]XLISV]ERHQEXLIQEXMGEPFMSPSK] [IEVIHIZIPSTMRKGSQTYXEXMSREPERHXLISVIXMGEPQIXLSHW XSI\TPSVIXLIWIEVIEW ;IEVIMRZIWXMKEXMRKTVSXIMRIZSPYXMSRI\TPSVMRK[LEX XLIIZSPYXMSREV]VIGSVHGERXIPPYWEFSYXXLIIJJIGXSJ QYXEXMSRW;IEPWSYWIQSVIXLISVIXMGEPQSHIPWXSFIXXIV YRHIVWXERHLS[XLIIZSPYXMSRSJTVSXIMRWHIXIVQMRIH XLIMVSFWIVZIHTVSTIVXMIW;IWXYH]XLIIZSPYXMSRSJ ZMVYWIWWYGLEW,-:MRSVHIVXSFIXXIVYRHIVWXERHXLI[E] XLI]EGXRS[LS[XLI]QMKLXGLERKIMRXLIJYXYVIERH LS[XLI]EVIEFPIXSWLMJXJVSQSRILSWXXSERSXLIV;I EVIEPWSWXYH]MRKLS[LSVM^SRXEPKIRIXVERWJIVEJJIGXWXLI IZSPYXMSRSJFEGXIVMEJSGYWMRKSR[LIRXLIMRXIVIWXWSJXLI KIRIWERHXLISVKERMWQWGSR¾MGX )WXMQEXIHGLERKIMR½XRIWWQYPXMTPMIHF]X[MGIXLITSTYPEXMSR WM^IMRMR¾YIR^E4&TVSXIMRJSPPS[MRKLSWXWLMJXXSLYQERW6IH distribution is for locations involved in adaptation to humans. Publications 4SPPSGO((8LMPXKIR+ERH+SPHWXIMR6% Amino acid coevolution induces an evolutionary Stokes shift. Proceedings of the National Academy of Sciences of the United States of America 109)) 8EQYVM%9HSW6IMW1ERH+SPHWXIMR6% )WXMQEXMRKXLIHMWXVMFYXMSRSJWIPIGXMSRGSIJ½GMIRXWJVSQTL]PSKIRIXMGHEXEYWMRKWMXI[MWI mutation-selection models. Genetics 190 +SPHWXIMR6% The evolution and evolutionary consequences of marginal thermostability in proteins. Proteins 79 Simulation showing evolution of two distinct clusters of plasmids, one with low horizontal transfer rate (m) and restrained replication g), the other with high horizontal transfer rate and unregulated replication. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 63 STRUCTURAL BIOLOGY Physical Biochemistry Ed Hulme Structure and function of G protein-coupled receptors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´WHMWIEWI ERHWGLM^STLVIRMEERHQE]HIGVIEWIEQ]PSMHTPEUYI JSVQEXMSR;IEVIJSGYWMRKSRRSZIPQSHIWSJMRXIVEGXMSR SJPMKERHW[LMGLLEZIZIV]LMKLWIPIGXMZMXMIWJSV1 Q%'L6W[SVOMRKXS[EVHWEXSQMGVIWSPYXMSRWXVYGXYVIW F]<VE]GV]WXEPPSKVETL]8LIWI[MPPTVSZMHIE½VQFEWMWJSV WXVYGXYVIFEWIHHVYKHIWMKR Publications ,YPQI)' GPCR activation: a mutagenic spotlight on crystal structures. Trends in Pharmacological Sciences 34, /E]I6+7EPHERLE.;0Y>0ERH,YPQI)' Helix 8 of the M1 muscarinic acetylcholine receptor: scanning mutagenesis delineates a G protein recognition site. Molecular Pharmacology 79 0IFSR+0ERKQIEH'.8ILER&+ERH,YPQI)' Mutagenic mapping suggests a novel binding mode for selective agonists of M1 muscarinic acetylcholine receptors. Molecular Pharmacology 75 Novel binding interactions (green) open up a bitopic binding mode for selective agonists of M1 muscarinic receptors. 64 MRC National Institute for Medical Research STRUCTURAL BIOLOGY Physical Biochemistry Justin Molloy Single molecule studies of cell motility and cell signalling 0EFQIQFIVW7YPIQER&E[YQME6EGLIP*EVVS[%RHVI[,S[I7XITLIR1EVXMR+VIKSV]1EWLERSZ4EYP1SSH]1EVX]R7XSTTW %PKMVHEW8SPIMOMW 8LITVMRGMTEPKSEPSJXLIKVSYTMWXSYRHIVWXERHXLI QSPIGYPEVQIGLERMWQSJJSVGITVSHYGXMSRF]EGXSQ]SWMR ERHLS[TVSXIMRWERHSVKERIPPIWQSZIEVSYRH[MXLMRPMZMRK GIPPW0EWIVFEWIHSTXMGEPQIXLSHWPMOISTXMGEPX[II^IVWERH XSXEPMRXIVREPVI¾IGXMSR¾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´WKVSYT)\IXIV &MSPSK](ITEVXQIRX[IMQEKIHMRHMZMHYEPQSPIGYPIWSJER YRYWYEPJYRKEPQ]SWMR<:--QSXSVSRWMRKPIEGXMR½PEQIRXW 8LI[SVOGSRXVMFYXIHXSSYVYRHIVWXERHMRKSJLS[XLMW QSXSVEGXWXSXIXLIVMXWGEVKSEXXLIGIPPTIVMTLIV][LMGLMW GVMXMGEPXSMXWVSPIMRPSGEPMWMRKGLMXMRW]RXLEWIEGXMZMX]EXXLI KVS[MRKXMTSJJYRKEPL]TLEI*MKYVI Figure 2. Left panel: Image series showing transient binding of myosin XVII (green) to F-actin (red). Right panel: Kymograph shows myosin XVII binds WTIGM½GEPP]XSEGXMRJSVbW but does not translocate. Publications *EVVS[6)+VIIR./EXMWQMXWSYPME>8E]PSV;6,SPHIV%%ERH1SPPS].) The mechanism of erythrocyte invasion by the malarial parasite, Plasmodium falciparum. Seminars in Cell & Developmental Biology 22 1SSH]47QMXL1)&6]ER'4'LYHEWEQE:&EOIV.61SPPS].ERH'EHHMGO7 Bromomaleimide-linked bioconjugates are cleavable in mammalian cells. Chembiochem : a European journal of chemical biology 13 Figure 1. We microinjected single cells with a bromomaleimide linked rhodamine-GFP conjugate and found that the sessile bond is cleaved in the reducing cytosolic milieu. 7GLYWXIV18VIMXWGLOI7/MPEVY71SPPS].,EVQIV2.ERH7XIMRFIVK+ Myosin-5, kinesin-1 and myosin-17 cooperate in secretion of fungal chitin synthase. EMBO Journal 31 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR MRC National Institute for Medical Research 65 STRUCTURAL BIOLOGY STRUCTURAL BIOLOGY Molecular Structure Physical Biochemistry John Offer Synthetic protein laboratory: acyl transfer for chemical biology and synthesis 0EFQIQFIVW'EVSPMRI1SVVMW+ISVKI4ETEKISVKMSY 4VSXIMRWEVIRS[[MXLMRXLIW]RXLIXMGVIEGLSJSVKERMGGLIQMWXV]8LIGSQFMREXMSRSJ WSPMHTLEWITITXMHIW]RXLIWMWERHXLIIQIVKMRKXIGLRSPSK]SJFMSPSKMGEPP]GSQTEXMFPI PMKEXMSRVIEGXMSRWMWETS[IVJYPSRIJSVXLIW]RXLIWMWSJWQEPPTVSXIMRW'LIQMGEP W]RXLIWMWMWTSXIRXMEPP]ERMQTSVXERXGSQTPIQIRXEV]QIXLSHXSFMSPSKMGEPI\TVIWWMSR JSVXLITVSHYGXMSRSJTSWXXVERWPEXMSREPP]QSHM½IHTVSXIMRWJSVXLIMRXVSHYGXMSRSJ RSRREXYVEPEQMRSEGMHWSVJSVWMXIWTIGM½GTVSXIMRPEFIPPMRK8LIVIWIEVGLEVIESJ PMKEXMSRLEWTS[IVJYPETTPMGEXMSRWFI]SRHTITXMHIQIXLSHSPSK]MRHVYKHMWGSZIV] W]RXLIXMGGLIQMWXV]ERHGLIQMGEPFMSPSK]XLIPEXXIVFIMRKETVMRGMTEPEVIESJJSGYW 4ITXMHIPMKEXMSRMWHITIRHIRXSRXLITVIWIRGISJG]WXIMRIEXXLIPMKEXMSRNYRGXMSR;I LEZIWLS[RXLEXF]EKIRIVEPGLIQMGEPQSHM½GEXMSRSJETITXMHIXIVQMRYW[IGER QEOIMXQMQMGXLIPMKEXMSRTVSTIVXMIWSJG]WXIMRI8LMWI\TERHWXLIW]RXLIXMG¾I\MFMPMX] SJXLIPMKEXMSRETTVSEGLWSXLEX[IGERQSVIIEWMP]VIEWWIQFPITVSXIMRWJVSQXLIMV GSQTSRIRXTITXMHIW8LIWIVIEGXMSRWEVIFIMRKI\TPSVIHXLVSYKLFSXLTVSXIMR W]RXLIWMWFMSGSRNYKEXMSRERHQSVIKIRIVEPP]XLVSYKLSVKERMGW]RXLIWMWXSEQMHI GSRXEMRMRKREXYVEPTVSHYGXW;IEVIW]RXLIWMWMRKWIZIVEPI\GMXMRKTVSXIMRXEVKIXW MRGPYHMRKLSQSKIRSYWGLIQMGEPP]HI½RIHKP]GSTVSXIMRWERHWIPJEWWIQFPMRKTVSXIMRW Synthesis of Bovine Pancreatic Trypsin Inhibitor (BPTI). a. Mass Spec. of BPTI b. HPLC time course of ligation reaction C = BPTI product, A = BPTI(137) and B = BPTI(38-58). Publications &YVPMRE*1SVVMW'&ILVIRHX6;LMXI4ERH3JJIV. Simplifying native chemical ligation with an N-acylsulfonamide linker. Chemical Communications 48 ,SPQ0%GOPERH+0)H[EVHW16&VIGOIRVMHKI6%7MQ6&ERH 3JJIV. Chemical labelling of active serum thioester proteins for UYERXM½GEXMSR Immunobiology 217 7GERPER'23JJIV.>MX^QERR2ERH([IO6% Exploiting the defensive sugars of HIV-1 for drug and vaccine design. Nature 446 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR 66 MRC National Institute for Medical Research Amide ester equilibrium. STRUCTURAL BIOLOGY Molecular Structure Annalisa Pastore Understanding the molecular bases of neurodegeneration 0EFQIQFIVW 7EPZEXSVI%HMRSP½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´WEXE\ME;IGSQTEVIHXLIVSPI SJXLITVSXIMRMRTVSOEV]SXIWERHIYOEV]SXIW3YVHEXEGSR½VQIH SYVTVIZMSYWSFWIVZEXMSRWXLEXJVEXE\MREGXWEWEVIKYPEXSVSJ MVSRWYPTLYVGPYWXIVJSVQEXMSRFYXEPWSTSMRXIHSYXMQTSVXERX HMJJIVIRGIWXLEXWYKKIWXXLIMVSRWYPTLYVGPYWXIVEWWIQFP] QEGLMRIV]XSFIERYRYWYEPI\EQTPIMR[LMGLQSHM½GEXMSRWXSER IR^]QIHYVMRKIZSPYXMSRMRZIVXWSVVIZIVWIWXLIQSHISJGSRXVSP MQTEVXIHF]EVIKYPEXSV]QSPIGYPI ;ILEZIEPWSJYVXLIVEHZERGIHSYVWXYHMIWSJEXE\MRXLITVSXIMR VIWTSRWMFPIJSVWTMRSGIVIFIPPEVEXE\MEX]TI;IWSPZIHXLI WXVYGXYVISJEGSQTPI\SJXLI%<,HSQEMRSJEXE\MRERHXLI TVSXIMR[LMGLWYKKIWXWERMQTSVXERXVSPISJXLMWMRXIVEGXMSR MRXLIRSVQEPERHTEXLSPSKMGJYRGXMSRSJXLITVSXIMR Publications %HVSZIV11EVXSVIPP+1EVXMR769VSWIZ(/SREVIZ4: 7ZIVKYR(-(EYVE<8IQYWWM4ERH4EWXSVI% The role of hydration in protein stability: comparison of the cold and heat unfolded states of Yfh1. Journal of Molecular Biology 417 &VMH[IPP6EFF.-ERRY^^M'4EWXSVI%ERH&EVSRHIEY(4 Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis. Biochemistry 51¯ 4EY[IPW/;MPPMEQW801SVVMW/0.SRGOLIIVI;:ERHIVWXIIR %/IPP]+7GL]QOS[MX^.6SYWWIEY*4EWXSVI%7IVTIPP0' ERH&VSIVWIR/ Structural basis for increased toxicity of pathological A`42:A`40 ratios in Alzheimer’s disease. Journal of Biological Chemistry 287 Model of the role of prokaryotic and eukaryotic frataxin (CyaY and FXN respectively) in Fe–S assembly. Frataxin forms a complex with the desulphurase enzyme that exists as a mixture of functional and nonfunctional states that are stabilised by binding of frataxin homologues. 7IIVIJIVIRGIW ERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 67 STRUCTURAL BIOLOGY Molecular Structure Andres Ramos Molecular recognition in post-transcriptional regulation 0EFQIQFIVW/EXLIVMRI'SPPMRW'LVMWXSTLIV+EPPEKLIV(EZMH,SPPMRK[SVXL2IWWMQ/MGLMO:MNE]EPE\QM1ERSLEVERGiuseppe Nicastro 4SWXXVERWGVMTXMSREPGSRXVSPTPE]WEOI]VSPIMRI\TERHMRK KIRSQMGHMZIVWMX]MRGSQTPI\SVKERMWQWERHHIVIKYPEXMSR SJXLIQIXEFSPMWQSJWTIGM½GQ62%WPMIWEXXLIFEWMWSJ GSQQSRKIRIXMGHMWIEWIWGERGIVEYXSMQQYRITEXLSPSKMIW ERHZMVEPMRJIGXMSR3YVKSEPMWXSI\TPEMRLS[62%FMRHMRK TVSXIMRWEGLMIZIERHVIKYPEXIXEVKIXWIPIGXMZMX]ERHLS[XLI] GSRXVSPXLII\TVIWWMSRSJWYFWIXWSJKIRIW;IGSQFMRI information obtained from NMR experiments with that SFXEMRIHF]SXLIVFMSTL]WMGEPWXVYGXYVEPXIGLRMUYIWERHF]MR GIPPin vivo EWWE]W 0IXMWEOI]VIKYPEXSVSJGIPPYPEVTVSPMJIVEXMSRERHMR LYQERWJYRGXMSRWEWERMQTSVXERXXYQSVWYTTVIWWSV 3YVVIGIRX[SVOSRXLIFMSKIRIWMWSJ0IXQM62% TVIGYVWSVLEWVIZIEPIHLS[XLIKIRIVEP62%VIKYPEXSV /764VIGSKRM^IWXLITVIQM62%ETMGEPPSSTMRGVIEWMRK TVIQM62%TVSGIWWMRKXSXLIQEXYVI0IX6IGSKRMXMSR MWEGLMIZIHF]ERSZIPQSHISJMRXIVEGXMSRFIX[IIR/, HSQEMRWERH62%[LMGLMRZSPZIVIQSHIPPMRKSJ0IX ETMGEPPSST3YVHEXEWLS[XLEXXLIPSSTW[MXGLIWFIX[IIR a form bound by the KSRP activator to one bound by the 0MRVITVIWWSVLMRXMRKXLEXEGXMRKSRXLIPSSTGSRJSVQEXMSR QE]VITVIWIRXEXSSPXSVIKYPEXI0IXGSRGIRXVEXMSRMRXLI GIPP Regulation of Let-7 miRNA biogenesis by KSRP. Publications 2MGEWXVSIXEP Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis. Nature Structural & Molecular Biology 19 'YOMIV'(,SPPMRK[SVXL(1EVXMR76/IPP]+(uE^1SVIRS-ERH6EQSW% Molecular basis of FIR-mediated c-myc transcriptional controP Nature Structural & Molecular Biology 17 8VEFYGGLM1&VMEXE4+EVGME1E]SVEP1,EEWI%(*MPMTS[MG^;6EQSW%+LIV^M6ERH6SWIRJIPH 1+ The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs. Nature 459 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 68 MRC National Institute for Medical Research Structure of KSRP KH3 in complex with the key recognition element of Let-7 miRNA precursor (in yellow). STRUCTURAL BIOLOGY Molecular Structure Katrin Rittinger Structural biology of signalling networks that regulate innate and adaptive immunity 0EFQIQFIVW2MGLSPEW&VS[R1ERYIPE,IWW%]PMR1SVVMW(EZMIW6SLMRM6ERE/SZMPIR7E[Q]REHIR&IR7XMIKPMX^ 4EXXIVRVIGSKRMXMSRVIGITXSVW466WEVIOI]GSQTSRIRXW SJXLIMRREXIMQQYRIW]WXIQXLEXWIRWIQMGVSFMEPERHZMVEP MRJIGXMSRWERHMRMXMEXIETVSMR¾EQQEXSV]VIWTSRWI8LIWMKREPPMRK TEXL[E]WEGXMZEXIHF]XLIWIVIGITXSVWRIIHXSFIXMKLXP] GSRXVSPPIHEWQMWVIKYPEXMSRGERPIEHXSGLVSRMGMR¾EQQEXMSR ERHEYXSMQQYRIHMWIEWI3YVVIWIEVGLMWJSGYWIHSRXLI WXVYGXYVEPGLEVEGXIVMWEXMSRSJTVSXIMRGSQTPI\IWXLEXVIKYPEXI MRREXIMQQYRMX]ERHMR¾EQQEXSV]VIWTSRWIW-RTEVXMGYPEV[I EVIMRXIVIWXIHMRYRHIVWXERHMRKLS[QIQFIVWSJXLI23( PMOIVIGITXSV206JEQMP]SJMRXVEGIPPYPEV466WVIGSKRMWIXLIMV XEVKIXWERHVIPE]XLMWMRJSVQEXMSRXSMRHYGIEWTIGM½GGIPPYPEV VIWTSRWI 9FMUYMXMREXMSRLEWIQIVKIHEWEOI]VIKYPEXSV]IPIQIRXMRXLI GSRXVSPSJMQQYRIERHMR¾EQQEXSV]WMKREPPMRKTEXL[E]W8LI X]TISJYFMUYMXMRGLEMREXXEGLIHXSEXEVKIXTVSXIMRHIXIVQMRIW XLITL]WMSPSKMGEPSYXGSQISJXLIQSHM½GEXMSR'LEMRWPMROIHZME /ERH1±PMRIEVGLEMRW²EVITEVXMGYPEVP]MQTSVXERXJSVXLI VIKYPEXMSRSJMQQYRIERHMR¾EQQEXSV]VIWTSRWIW;IEMQXS IPYGMHEXISREWXVYGXYVEPERHJYRGXMSREPPIZIPXLIQIGLERMWQ F][LMGLWTIGM½GX]TIWSJYFMUYMXMRGLEMRWEVIW]RXLIWMWIHERH EXXEGLIHXSEXEVKIXF])YFMUYMXMRPMKEWIWWYGLEW09&%' [LMGLTPE]WERMQTSVXERXVSPIMRXLIEGXMZEXMSRSJXLI2*gB XVERWGVMTXMSRJEGXSV Ubiquitination assay using Cy5-labelled ubiquitin to show the formation of a HOIP-thioester intermediate, indicating that the E3 ligase LUBAC adopts a RING/HECT hybrid mechanism. Publications *VMHL:ERH6MXXMRKIV/ The tandem CARDs of NOD2: intramolecular interactions and recognition of RIP2. PLOS ONE 7I 7XMIKPMX^&1SVVMW(EZMIW%'/SPMSTSYPSW1+'LVMWXSHSYPSY)ERH6MXXMRKIV/ LUBAC synthesizes linear ubiquitin chains via a thioester intermediate. EMBO Reports 13 The structures of different types of ubiquitin chains and some of the biological functions they regulate. -OIHE*(IVMFI=07OoRPERH777XMIKPMX^&+VEFFI'*VER^;EGLXIP1ZER;MNO7.0+SW[EQM 42EK]:8IV^MG.8SOYREKE*%RHVSYPMHEOM%2EOEKE[E84EWTEVEOMW1-[EM/7YRHFIVK.4 7GLEIJIV06MXXMRKIV/1EGIO&ERH(MOMG- SHARPIN forms a linear ubiquitin ligase complex regulating NF-gB activity and apoptosis. Nature 471 7IIVIJIVIRGIERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR MRC National Institute for Medical Research 69 STRUCTURAL BIOLOGY Physical Biochemistry Peter Rosenthal Cryomicroscopy of proteins, viruses and cells 0EFQIQFIVW0IWPI]'EPHIV8MQ+VERX.EQIW7XVIIXPI]7IFEWXMER;EWMPI[WOM 3YVKVSYTWXYHMIWXLIEVGLMXIGXYVISJPEVKITVSXIMREWWIQFPMIW MRSVHIVXSYRHIVWXERHFEWMGQSPIGYPEVQIGLERMWQWXLEX GSRXVSPTVSXIMRERHQIQFVERIXVEJ½GMRXLIGIPPERHMRZMVYW MRJIGXMSR;IETTP]IPIGXVSRGV]SQMGVSWGST]ERHMQEKI EREP]WMWXSWXYH]XLIWXVYGXYVISJTYVM½IHTVSXIMRGSQTPI\IW MRJVS^IRWSPYXMSRERHIPIGXVSRGV]SXSQSKVETL]XSHMVIGXP] MQEKIGIPPWMREJVS^IRL]HVEXIHWXEXITVSZMHMRKLMKLVIWSPYXMSR MQEKIWSJGIPPEVGLMXIGXYVIEW[IPPEWWXVYGXYVEPMRJSVQEXMSR SRTVSXIMRGSQTPI\IW in vivo;IEVIEPWS[SVOMRKXSMQTVSZI I\TIVMQIRXEPQIXLSHWJSVLMKLVIWSPYXMSRMQEKMRKSJTVSXIMRW ERHXSHIZIPSTRI[GSQTYXEXMSREPTVSGIHYVIWJSVMQEKI EREP]WMW ;ILEZITIVJSVQIHLMKLVIWSPYXMSRGV]SQMGVSWGST]SJ MR¾YIR^EZMVYWVIZIEPMRKXLIWXVYGXYVISJXLIZMVYWIRZIPSTI ERHXLIMRXIVREPEVGLMXIGXYVISJXLIZMVYW;IEPWSWXYH]LS[ ZMVYWIWIRXIVGIPPWF]QIQFVERIJYWMSRERHLS[RI[TEVXMGPIW EVIEWWIQFPIHERHVIPIEWIHF]FYHHMRKXLVSYKLXLILSWX QIQFVERI-RSYVWXYHMIWSJGIPPEVGLMXIGXYVI[ILEZIFYMPX WXVYGXYVEPQSHIPWJSV;IMFIP4EPEHIFSHMIW[LMGLEVIWXSVEKI KVERYPIWJSVZSR;MPPIFVERHJEGXSVERHWXYH]XLIMVWXVYGXYVEP GLERKIWHYVMRKI\SG]XSWMW -QEKISJJVS^IRL]HVEXIHMR¾YIR^EZMVYW Publications &IVVMQER.%ERH6SWIRXLEP4& Paraxial charge compensator for electron cryomicroscopy. Ultramicroscopy 116 ;EWMPI[WOM7'EPHIV0.+VERX8ERH6SWIRXLEP4& (MWXVMFYXMSRSJWYVJEGIKP]GSTVSXIMRWSRMR¾YIR^E%ZMVYWHIXIVQMRIHF]IPIGXVSR cryotomography. Vaccine 30 &IVVMQER.%0M7,I[PIXX0.;EWMPI[WOM7/MWOMR*2'EVXIV8,ERREL1.ERH6SWIRXLEP4& 7XVYGXYVEPSVKERM^EXMSRSJ;IMFIP4EPEHIFSHMIWVIZIEPIHF]GV]S)1SJZMXVM½IHIRHSXLIPMEP cells. Proceedings of the National Academy of Sciences of the United States of America 106: 70 MRC National Institute for Medical Research Weibel-Palade bodies inside an endothelial cell. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYT MR STRUCTURAL BIOLOGY Molecular Structure Steve Smerdon EMBO member Structural biology of phosphorylation-dependent signalling in the cell cycle and DNA 0EFQIQFIVW.YPMI'PETTIVXSR3PMZIVHI4I]IV8SQ*PS[IV1SLEQIH-WQEMP3XXS/]VMIPIMW6MGLEVH0M.ER0PS]H7MQSR4IRRIPP 0EWWI7XEGL+VEGI=Y 8LIH]REQMGREXYVISJGIPPYPEVWMKREPPMRKTVSGIWWIWVIUYMVIWXLIQ XSFIVETMHP]VIZIVWMFPIEGLEVEGXIVMWXMGXLEXMWKIRIVEPP]EGLMIZIH XLVSYKLTVSXIMRTLSWTLSV]PEXMSR8LIVIWTSRWIXS(2%HEQEKI MWQIHMEXIHF]EGEWGEHISJTLSWTLSV]PEXMSRXLEXSVMKMREXIWEXXLI PIWMSRERHMWXVERWHYGIHXSIJJIGXSVQSPIGYPIWERHGSQTPI\IW (IJIGXWMRXLITVIGMWMSRSJTLSWTLSV]PEXMSREVIETVMQEV]GEYWISJ QER]GERGIVWERHSXLIVHMWIEWIW&]YRHIVWXERHMRKXLIQSPIGYPEV FEWMWSJWTIGM½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´WPEFMR3\JSVH[ILEZIFIIR EFPIXSWLS[LS[4POTVMQIW'/TLSWTLSV]PEXMSRSJERSZIP VIKYPEXSV]WMXIMR6EHXLEXYPXMQEXIP]VIGVYMXW2FWXSWMXIWSJ LSQSPSKSYWVIGSQFMREXMSRVITEMV A model for Rad51 recruitment to DNA-breaks. Publications .YRKQMGLIP7'PETTIVXSR.%0PS]H.,EVM*.7T]GLIV'4EZMG00M.,EMVI0* &SREPPM10EVWIR(,0YOEW'0YOEW.1EGQMPPER(2MIPWIR107XYGOM1ERH 7QIVHSR7. The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator. Nucleic Acids Research 40 =EXE/0PS]H.1EWPIR7&PIY]EVH.=7OILIP17QIVHSR7.ERH)WEWLM* Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair. Molecular Cell 45 ATM-dependent Mdc1 FHA dimerisation regulates interactions crucial for DNA-damage signalling. 0PS]H.'LETQER.6'PETTIVXSR.%,EMVI0*,EVXWYMOIV)0M.'EVV%1.EGOWSR 74ERH7QIVHSR7. A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage. Cell 139 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 71 STRUCTURAL BIOLOGY Molecular Sructure Ian Taylor Macromolecular assemblies 0EFQIQFIVW0EYVIRGI%VRSPH2IMP&EPP:EPIVMI)RRMW%HIRMVER0EYVE6SFIVXWSR(EZMH7GL[IJIP 1ER]SJXLIJYRHEQIRXEPTVSGIWWIWGEVVMIHSYX[MXLMRPMZMRK GIPPWEVIHMVIGXIHF]QEGVSQSPIGYPEVEWWIQFPMIWSJTVSXIMR ERHRYGPIMGEGMHQSPIGYPIWSJXIRVIJIVVIHXSEW±QSPIGYPEV QEGLMRIW²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´IRH TVSGIWWMRKERHTSP]EHIR]PEXMSREREP]WMWSJXLIMRXIVEGXMSRSJ XLIVIXVSZMVEPGETWMH[MXLLSWXJEGXSVWERHWXVYGXYVEPWXYHMIWSJ LSWXGIPPERXMVIXVSZMVEPVIWXVMGXMSRJEGXSVW Left, the structure of the RELIK capsid (blue) bound to the host cell factor CypA (green). Details of the RELIK-CypA molecular interface are shown on the right. Publications +SPHWXSRI(')RRMW%HIRMVER:,IHHIR..+VSSQ,'86MGI+-'LVMWXSHSYPSY);EPOIV4%/IPP]+ ,EMVI0*=ET1;HI'EVZEPLS047XS]I.4'VS[=.8E]PSV-%ERH;IFF1 HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480 ,MPHMXGL01EXEHIIR6+SPHWXSRI('6SWIRXLEP4&8E]PSV-%ERH7XS]I.4 3VHIVIHEWWIQFP]SJQYVMRIPIYOIQMEZMVYWGETWMHTVSXIMRSRPMTMHRERSXYFIWHMVIGXWWTIGM½GFMRHMRK by the restriction factor, Fv1. Proceedings of the National Academy of Sciences of the United States of America 108¯ +SPHWXSRI('=ET1;6SFIVXWSR0),EMVI0*8E]PSV;6/EX^SYVEOMW%7XS]I.4ERH8E]PSV-% Structural and functional analysis of prehistoric lentiviruses uncovers an ancient molecular interface. Cell Host & Microbe 8 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQ XLMWKVSYTMR 72 MRC National Institute for Medical Research Left, structure of the HIV-1 restriction factor SAMHD1 with bound dGTP. The molecular details of the linkage between the allosteric and active sites are shown on the right. STRUCTURAL BIOLOGY Mathematical Biology Willie Taylor Protein structure analysis and design 0EFQIQFIVW1MGLEIP(SVER/EXEV^]RE1EOWMQMEO1MGLEIP7EHS[WOM 4VSXIMRWEVIXLIQEMRIWWIRXMEPEGXMZIEKIRXWMRFMSPSK] ERH[MXLSYXXLIQEPQSWXRSRISJXLITVSGIWWIWXLEX[I EWWSGMEXI[MXLPMJI[SYPHXEOITPEGI4VSXIMRWIREGXXLIMV XEWOWRSXEWXLIPMRIEVWIUYIRGISJEQMRSEGMHWXLEXHI½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½FVI*MKYVITEVXEERH 6IJ8LIETTVSEGLLEWWMRGIFIIRKIRIVEPMWIHXSEPPS[ QYPXMTPIPIZIPWERHMWRSXPMQMXIHXSQSHIPPMRKTVSXIMRW[MXL EVIGIRXETTPMGEXMSRFIMRKXSWMQYPEXITSTYPEXMSRWSJGIPPW *MKYVITEVXFERH6IJ%W[IPPEWXLIWIHVMZIRW]WXIQW XLIQSHIPPMRKXSSPWLSYPHFIIUYEPP]ETTPMGEFPIXSTEWWMZI W]WXIQWWYGLEWKYMHMRKXLIEWWIQFP]SJHSQEMRWTVIHMGXIH YWMRKTVIHMGXIHGSRXEGXW6IJERHWMKREPPMRKRIX[SVOWMR TEVXMGYPEVXLSWI[LIVIWTEXMEPI\GPYWMSRMWMQTSVXERX Publications /EXWMQMXWSYPME>ERH8E]PSV;6 Coarse-grained simulation of myosin-V movement. Computational and Mathematical Methods in Medicine 781456 7EHS[WOM1- Prediction of protein domain boundaries from inverse covariances. Proteins: Structure, Function, and Bioinformatics 81 8E]PSV;61SVPI]6/VEWEZMR%+VIKSV]0;MPOMRWSR(+ERH4SPMEOSZ% A mechanical model of cell segregation driven by differential adhesion. PLOS ONE 7I Simulations made with the multi-level modelling program: a) a myosin-V dimer (red) on a circular track of actin (green). Secondary structure elements are short rods and domains are spheres: b) The same program simulating the segregation of Eph/ephrin expressing cells. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 73 STRUCTURAL BIOLOGY Physical Biochemistry Martin Webb The molecular mechanisms of motor proteins 0EFQIQFIVW'PEYHME%VFSVI0MMWE'LMWX]'SPMR(EZMW7MQSRI/YR^IPQERR+SVHSR6IMH.IV^]7EQSPIN0IWPI]7SYXLIVHIR 1SZIQIRXSJTVSXIMRWEPSRK(2%MWERIWWIRXMEPJIEXYVISJGIPPW JSVI\EQTPISGGYVVMRKHYVMRK(2%VITPMGEXMSRERHVITEMV,IPMGEWIW EVIIR^]QIWXLEXQSZIEPSRKHSYFPIWXVERHIH(2%WITEVEXMRKXLI WXVERHWWSQEOMRKXLIQEZEMPEFPIJSVJYVXLIVTVSGIWWMRK*SVGSVVIGX GIPPQEMRXIRERGIERHHMZMWMSRMXMWIWWIRXMEPXLEXXLIVIMWXMKLXGSRXVSP SJWYGLTVSGIWWMRK;IEVIMRXIVIWXIHMRXLIQIGLERMWQERHGSRXVSP SJWYGLTVSGIWWIW;IEVIHIZIPSTMRKRI[STXMGEPETTVSEGLIWWYGLEW VIEKIRXPIWWFMSWIRWSVWFSXLXSWXYH]XLMWQSZIQIRXEPSRK(2%FYX EPWSXSHIZIPSTEWWE]WJSVE[MHIVERKISJIR^]QEXMGEGXMZMXMIW 3YVLIPMGEWITVSNIGXEMQWXSYRHIVWXERHEGSQTPIXIW]WXIQMR[LMGL XLILIPMGEWIMRXIVEGXW[MXLSXLIVTVSXIMRWEW[IPPEWQSZMRKXLVSYKL (2%;IEVIMRZIWXMKEXMRKXLIVITPMGEXMSRSJGIVXEMRTPEWQMHWXLEX GSRXEMRERXMFMSXMGVIWMWXERGIKIRIWERHXLEXEVIVIEHMP]XVERWJIVVIH FIX[IIRFEGXIVME7YGLVITPMGEXMRKTPEWQMHWGSRXEMREWTIGM½GHSYFPI WXVERHIHSVMKMRSJVITPMGEXMSRERHEVIFSYRH[MXLEVITPMGEXMSR MRMXMEXMSRJEGXSV6IT(LIPMGEWIERHTSP]QIVEWI&]GSRWXVYGXMRKXLMW system in vitro[IWXYH]XLIVSPIERHQIGLERMWQSJIEGLGSQTSRIRX 8LIHIZIPSTQIRXSJFMSWIRWSVWLEWMRGPYHIHSRIJSV%(4SV+(4 XLEXMWWYMXEFPIJSVVIEPXMQIEWWE]WERHLMKLXLVSYKLTYXETTVSEGLIW Publications %VFSVI'0I[MW01ERH;IFF16 The kinetic mechanism of initiation by RepD as part of asymmetric, rolling circle plasmid unwinding. Biochemistry 51¯ /YR^IPQERR7ERH;IFF16 Fluorescent detection of GDP in real time with the reagentless biosensor, rhodamine-ParM. Biochemical Journal 440 >LSY6/YR^IPQERR7;IFF16ERH,E8 Detecting intramolecular conformational dynamics of single molecules in short distance range with subnanometer sensitivity. Nano letters 11 4PEWQMHYR[MRHMRKF]4GV%LIPMGEWIERHMRMXMEXSVTVSXIMR6IT(QIEWYVIHYWMRK¾YSVIWGIRX77&ERH single molecule TIRFM. A. Experimental arrangement. B. Fluorescent spots development as SSB binds exposed single-stranded DNA. (Collaboration with Justin Molloy). 74 MRC National Institute for Medical Research 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR Neurosciences Developmental Neurobiology David Wilkinson (Head of Division) Siew-Lan Ang Molecular Neurobiology François Guillemot (Head of Division) Vassilis Pachnis Iris Salecker Neurophysiology Troy Margrie (Head of Division) Denis Burdakov Physiology and Metabolism Alex Gould (Head of Division) Dimitrios Anastasiou MRC National Institute for Medical Research 75 NEUROSCIENCES Physiology and Metabolism Dimitrios Anastasiou Cancer metabolism 'ERGIVGIPPWYXMPMWIRYXVMIRXWMREHMWXMRGXQERRIVGSQTEVIHXSQSWX RSVQEPGIPPW8LMWTLIRSQIRSRVI¾IGXWMRTEVXERMRGVIEWIHHIQERH JSVGIPPYPEVFYMPHMRKFPSGOWXSWYTTSVXTVSPMJIVEXMSREW[IPPEWERIIH XSHIEP[MXLXLIYRMUYIGLEPPIRKIWXLEXGERGIVGIPPWJEGIJVSQXLIMV IRZMVSRQIRX1]PEFMWMRZIWXMKEXMRKXLIQSPIGYPEVQIGLERMWQWXLEX YRHIVPMIXLIGLEVEGXIVMWXMGQIXEFSPMWQSJXYQSYVW-EQJYVXLIV MRXIVIWXIHMRYRHIVWXERHMRKLS[XLIQIXEFSPMGJIEXYVIWSJMRHMZMHYEP GIPPX]TIW[MXLMRXLIXYQSYVRMGLIMR¾YIRGIGERGIVHIZIPSTQIRX 8LIWIWXYHMIWEVIGSQTPIQIRXIHF]WXVYGXYVIFEWIHHIWMKRSJ QSPIGYPEVFMSWIRWSVWXSTVSFIQIXEFSPMWQin vivoEXXLIWMRKPIGIPP PIZIP 3RIEWTIGXSJQ]VIGIRX[SVOLEWJSGYWIHSRXLIKP]GSP]XMG IR^]QI4/1-WLS[IHXLEX4/1LIPTWGERGIVGIPPWWYVZMZIYRHIV S\MHEXMZIWXVIWWIPMGMXIHF]PS[S\]KIRGSRGIRXVEXMSRWL]TS\MEE GSRHMXMSRSJXIRIRGSYRXIVIHMRXYQSYVWF]EPXIVMRKXLI[E]XLI] QIXEFSPM^IKPYGSWI7QEPPQSPIGYPIEGXMZEXSVWSJ4/1HMWVYTXXLMW TVSGIWWXSMQTIHITVSPMJIVEXMSRERHWIRWMXMWIGERGIVWXSS\MHERX MRHYGIHHIEXL1]VIWYPXWMRHMGEXIXLEXEGXMZEXMSRSJ4/1GSYPHFI EYWIJYPXLIVETIYXMGETTVSEGLJSVEFVSEHWTIGXVYQSJGERGIVWERH WYKKIWXGPMRMGEPWIXXMRKW[LIVI4/1EGXMZEXSVWGSYPHFIIJJIGXMZIP] GSQFMRIH[MXLI\MWXMRKHVYKWXSMQTVSZIXLIMVXLIVETIYXMGTSXIRXMEP Re-programming of glucose metabolism supports antioxidant responses following oxidative stress. PKM2 activators abrogate this homeostatic mechanism. Publications %REWXEWMSY(ERH'ERXPI]0' Breathless cancer cells get fat on glutamine. Cell Research 22 %REWXEWMSY(=Y=-WVEIPWIR;..MERK./&S\IV1&,SRK&78IQTIP;(MQSZ77LIR1.LE%=ERK ,1EXXEMRM/61IXEPPS'1*MWOI&4'SYVXRI]/(1EPWXVSQ7/LER81/YRK'7OSYQFSYVHMW %4:IMXL,7SYXLEPP2;EPWL1.&VMQEGSQFI/60IMWXIV;0YRX7=.SLRWSR>6=IR/)/YRMM/ (EZMHWSR71'LVMWXSJO,6%YWXMR'4-RKPIWI.,EVVMW1,%WEVE.17XITLERSTSYPSW+7EPMXYVS *+.MR7(ERK0%YPH(74EVO,;'ERXPI]0'8LSQEW'.ERH:ERHIV,IMHIR1+ Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nature Chemical Biology 8: %REWXEWMSY(4SYPSKMERRMW+%WEVE.1&S\IV1&.MERK./7LIR1&IPPMRKIV+7EWEOM%80SGEWEPI .;%YPH(78LSQEW'.:ERHIV,IMHIR1+ERH'ERXPI]0' Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science 334 76 MRC National Institute for Medical Research Structure of PKM2 showing the distinct binding pockets of the natural allosteric activator, FBP and a synthetic one, DASA-2. (PDBID:3GQY). NEUROSCIENCES Developmental Neurobiology Siew-Lan Ang 2IYVSREPWYFX]TIWTIGM½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½RHMRKWLEZI HMVIGXQIHMGEPVIPIZERGIWMRGIPSWWSJQ(%RIYVSRWMWXLILEPPQEVOSJ 4EVOMRWSR´WHMWIEWIERHH]WJYRGXMSRSJJIIHMRKGMVGYMXWMRXLIFVEMRGER PIEHXSSFIWMX]MRLYQERW ;IGYVVIRXP]JSGYWSRYRHIVWXERHMRKLS[XLIHIZIPSTQIRXEP TVSKVEQQIWXLEXWTIGMJ]GIPPX]TIMHIRXMX]TVSZMHIEFPYITVMRXJSV HI½RMRKGSRRIGXMZMX]TEXXIVRW[LMGLYRHIVPMIHMWXMRGXERMQEPFILEZMSYVW We use mouse embryos and in vitro differentiation of mouse embryonic WXIQGIPPWXSMHIRXMJ]KIRIWXLEXVIKYPEXIXLIWTIGM½GEXMSRHMJJIVIRXMEXMSR ERH[MVMRKSJQ(%RIYVSRWERHEVGYEXITVSSTMSQIPERSGSVXMRERH RIYVSTITXMHI=3YVI\TIVMQIRXEPETTVSEGLIWMRGPYHIEGSQFMREXMSR SJIQFV]SPSKMGEPKIRIXMGQSPIGYPEVERHKIRSQMGETTVSEGLIWMRGPYHMRK KIRIXMGJEXIQETTMRKWXYHMIW RYPPERHGSRHMXMSREPQYXERX QMGIFVEMRWPMGIGYPXYVI IPIGXVSTL]WMSPSKMGEPVIGSVHMRKW FMSGLIQMGEPERHXVERWGVMTXSQI EREP]WIW8LIWIWXYHMIW[MPP TVSZMHIMRWMKLXWMRXSLS[ IQFV]SRMGKIRII\TVIWWMSR PIEHWXSQEXYVIRIYVSREP TLIRSX]TIW Molecularly distinct dopaminergic neurons in the midbrain of an adult mouse labelled with different ¾YSVSGLVSQIW:8%ZIRXVEPXIKQIRXEPEVIE Publications 1IX^EOSTMER)0MR;7EPQSR(MZSR1(ZMRKI,%RHIVWWSR))VMGWSR.4IVPQERR8;LMXWIXX.%&IVXSRI4ERH%RK70 +IRSQI[MHIGLEVEGXIVM^EXMSRSJ*S\EXEVKIXWVIZIEPWYTVIKYPEXMSRSJ¾SSVTPEXIKIRIWERHVITVIWWMSRSJZIRXVSPEXIVEPKIRIWMR midbrain dopaminergic progenitors. Development 139 4IPPMRK1%RXL[EP21G2E](+VEH[SLP+0IMXIV%&+YMPPIQSX*ERH%RK70 Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus. Developmental Biology 349 Working model of gene regulatory network involved in specifying midbrain dopaminergic neuron progenitor identity. =ER',0IZIWUYI1'PE\XSR7.SLRWSR60ERH%RK70 0Q\E ERH 0Q\F JYRGXMSR GSSTIVEXMZIP] XS VIKYPEXI TVSPMJIVEXMSR WTIGM½GEXMSR ERH HMJJIVIRXMEXMSR SJ QMHFVEMR HSTEQMRIVKMG progenitors. Journal of Neuroscience 31 MRC National Institute for Medical Research 77 NEUROSCIENCES Neurophysiology Denis Burdakov Intercellular signalling logic in brain and metabolic orchestration 0EFQIQFIVW'VEMK&PSQIP]7EVEL'EMRW'IHVMG*EYVI%RXSRMS+SR^EPI^'SRRM7GL}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½GRIYVSREP X]TIW;I[SVO[MXLXVERWKIRMGQSYWIQSHIPWERHWSQIXMQIW[MXL GSQTYXIVWMQYPEXIHZMVXYEPGIPPWERHGIPPW]WXIQW3RKSMRKTVSNIGXWEPWS YWIMQEKMRKIPIGXVSTL]WMSPSK]EREXSQMGEPXVEGMRKMQQYRSPEFIPPMRKERH [LSPIFSH]TL]WMSPSKMGEPEWWE]WXSI\TPSVIGPSWIP]MRXIVVIPEXIHXLIQIW 'IPPWERHQIGLERMWQWJSVMRXIVREPFSH]WXEXIWIRWMRK 6IKYPEXMSRSJ½VMRKTEXXIVRWERHXVERWQMXXIVVIPIEWIMR brain circuits -RTYXSYXTYXTVSTIVXMIWSJW]RETWIWGIPPWERHGMVGYMXW 1IXEFSPMGGLIQMGEPERHIPIGXVMGEPWMKREPPMRKMRXLIL]TSXLEPEQYW &VEMRERHFVEMRCbody orchestration %PXIVEXMSRWMRHMWSVHIVWSJFVEMRJYRGXMSRERHQIXEFSPMGFEPERGI Genetic targeting of “light-switches” such as excitatory ion channel ChR2 makes it possible to establish the consequences of millisecond-scale changes in HI½RIHIPIQIRXWSJ vital neurocircuits. Publications 7GL}RI''ES>*,%TIVKMW7GLSYXI.%HEQERXMHMW%7EOYVEM8ERH&YVHEOSZ( Optogenetic probing of fast glutamatergic transmission from hypocretin/orexin to histamine neurons in situ. Journal of Neuroscience 32 Widely-projecting orx and MCH neurons regulate sleep and energy balance, and are themselves regulated by ambient glucose. /EVRERM11%TIVKMW7GLSYXI.%HEQERXMHMW%.IRWIR08HI0IGIE0*YKKIV0ERH&YVHEOSZ( Activation of central orexin/hypocretin neurons by dietary amino acids. Neuron 72 ;MPPMEQW6,.IRWIR08:IVOLVEXWO]%*YKKIV0ERH&YVHEOSZ( Control of hypothalamic orexin neurons by acid and CO2. Proceedings of the National Academy of Sciences of the United States of America 104 78 MRC National Institute for Medical Research NEUROSCIENCES Physiology and Metabolism Alex Gould Regulation of growth and metabolism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¾YIRGMRKKVS[XL QIXEFSPMWQERHGERGIV ;IEVIGYVVIRXP]MRZIWXMKEXMRKLS[JIXEPQEPRYXVMXMSRHMJJIVIRXMEPP]EJJIGXWXLIKVS[XL SJFSH]SVKERW1YGLSJSYVVIWIEVGLMRXLMWEVIEYWIWXLIJVYMX¾]DrosophilaEQSHIP SVKERMWQXLEXWLEVIWQER]KIRIW[MXLQEQQEPW;IVIGIRXP]MHIRXM½IHEQIXEFSPMG KIRIRIX[SVOIRWYVMRKXLEXXLIKVS[XLSJXLIFVEMRMWWTEVIHSZIVXLEXSJSXLIV SVKERW[LIRRYXVMIRXWFIGSQIPMQMXMRK%XXLILIEVXSJXLMWRIX[SVOMW%RETPEWXMG 0]QTLSQE/MREWIEVIGITXSVXLEXMWI\TVIWWIHMRRIYVEPWXIQGIPPWMRXLILIEPXL] KVS[MRKFVEMRFYXMWEPWSEFRSVQEPP]L]TIVEGXMZEXIHMRGIVXEMRJEWXKVS[MRKGERGIVW 8SZMWYEPMWIERHXSUYERXMJ]QIXEFSPMWQMRWMHIMRHMZMHYEPGIPPW[MXLERYRTVIGIRHIRXIH WTEXMEPVIWSPYXMSR[ILEZIEPWSFIIRHIZIPSTMRKERI[QIXLSHSPSK]GEPPIHQYPXM MWSXSTIMQEKMRKQEWWWTIGXVSQIXV]1-17 Comparison of confocal microscope and multi-isotope imaging mass spectrometry (MIMS) images of lipid droplets inside Drosophila adipocytes (n indicates nucleus). Publications 7XIMRLEYWIV10&EMPI]%47IR]S7)+YMPPIVQMIV'4IVPWXIMR87+SYPH%40II68ERH0IGLIRI'4 1YPXMMWSXSTIMQEKMRKQEWWWTIGXVSQIXV]UYERXM½IWWXIQGIPPHMZMWMSRERHQIXEFSPMWQ Nature 481 'LIRK0=&EMPI]%40IIZIVW7.6EKER8.(VMWGSPP4'ERH+SYPH%4 Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell 146 7SYWE2YRIW6=II00ERH+SYPH%4 Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 471 1-17UYERXM½GEXMSRSJHMIXEV]JEX13C-palmitate) incorporation into the lipid droplets of Drosophila adipocytes (fat body) or enterocytes (gut) during 24 hour (h). MRC National Institute for Medical Research 79 NEUROSCIENCES Molecular Neurobiology François Guillemot Genomic and functional analysis of neurogenesis 0EFQIQFIVW%RKIPMOM%GLMQEWXSY.MQIRE%RHIVWIR6SFIVXE%^^EVM0ER'LIR4EXVMGME+EVGI^7IFEWXMIR+MPPSXMR%]EOS-XS &IR1EVX]RSKE'VMWXMRE1MRMIVM/SNM3MWLM2SIPME9VFER(IFFMIZERHIR&IVK&IRR]=ERK 2IYVEPWXIQGIPPWMRXLIHIZIPSTMRKERHEHYPXFVEMRTVSHYGI EZEWXEVVE]SJRIYVSRW[LMGLQMKVEXIXSWTIGM½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ublications 'EWXVS(71EVX]RSKE&4EVVEW'6EQIWL:4EGEV]) .SLRWXSR'(VIGLWIP(0IFIP4SXXIV1+EVGME0+,YRX '(SPPI(&MXLIPP%)XX[MPPIV0&YGOPI]2ERH+YMPPIQSX * A novel function of the proneural factor Ascl1 in progenitor TVSPMJIVEXMSRMHIRXM½IHF]KIRSQI[MHIGLEVEGXIVM^EXMSR of its targets. Genes & Development 25 4EGEV]),IRK.%^^EVIPPM66MSY4'EWXVS(0IFIP4SXXIV 14EVVEW'&IPP(16MHPI]%.4EVWSRW1ERH+YMPPIQSX * Proneural transcription factors regulate different steps of cortical neuron migration through Rnd-mediated inhibition of RhoA signaling. Neuron 69 Cultured neural stem cells induced into quiescence by Bone Morphogenetic Protein 4 and stained for the stem cell markers GFAP (green) and nestin (red) and the nuclear marker Dapi (blue). 80 MRC National National Institute Institute for for Medical Medical Research Research MRC Heatmap showing genomic regions in activated and quiescent neural stem cells that have characteristics of active enhancers as shown by the high levels of the histone mark acetylation of H3K27. ,IRK.-82KY]IR0'EWXVS(7>MQQIV';MPHRIV, %VQERX37OS[VSRWOE/VE[G^]O(&IHSKRM*1EXXIV.1 ,IZRIV6ERH+YMPPIQSX* Neurogenin 2 controls cortical neuron migration through regulation of Rnd2. Nature 455 NEUROSCIENCES Neurophysiology Troy Margrie Sensory processing in single cells, circuits and behavior 0EFQIQFIVW)H&VEGI]%PI\&VS[R'LVMWXMER2MIH[SVSO)HI6ERG^'LEVP]6SYWWIEY%RNE7GLQEPX^1SPP]7XVSQ1EXIS:IPI^*SVX 8LIFIRI½XSJHIXIGXMRKERHEGGYVEXIP]VIGSKRMWMRKSFNIGXW MRXLII\XIVREP[SVPHLEWFIIREOI]HVMZIVSJXLIIZSPYXMSR SJXLIGIRXVEPRIVZSYWW]WXIQ8LIRIYVSREPFEWMWSJ sensory representation in the brain therefore underpins LS[[IQEOIWIRWISJXLI[SVPHEVSYRHYWSYVEFMPMX]XS WSPZITVSFPIQWERHVIQIQFIVTEWXI\TIVMIRGIW3YVPEF MWJSGYWIHSRYRHIVWXERHMRKXLIJYRHEQIRXEPGIPPYPEVERH RIX[SVOFEWIHQIGLERMWQWXLEXYRHIVPMIXLIWIJYRGXMSRW ;IEVITEVXMGYPEVP]MRXIVIWXIHMRIWXEFPMWLMRKXLII\XIRXXS [LMGLKIRIVMGGMVGYMXWEVIYWIHXSSVGLIWXVEXIXLMWTVSGIWW ERHXLIFMSTL]WMGEPTVSTIVXMIWSJRIYVSRWIQFIHHIHMR XLIWIRIX[SVOWEVIQSHYPEXIHERHSTXMQMWIHXSTIVJSVQ WTIGM½GWIRWSV]GSQTYXEXMSRW We wish to understand how the brain uses the activity of MRHMZMHYEPRIYVSRWERHGSPPIGXMSRWSJRIYVSRWXSIRGSHI WIRWSV]WXMQYPM8SEGLMIZIXLMW[IYWIEXSTHS[R QYPXMHMWGMTPMREV]ETTVSEGLXLEXEPPS[WYWXSI\TPSVIXLMW JVSQXLIW]WXIQWXSXLIGIPPYPEVPIZIP7TIGM½GEPP][IEVI MRZIWXMKEXMRKWIZIVEPUYIWXMSRWM8S[LEXI\XIRXMWWIRWSV] representation distributed across primary and secondary or QYPXMQSHEPFVEMREVIEW#MM;LEXMJER]MWXLIVIPEXMSRWLMT FIX[IIRPSGEPRIYVSREPGSRRIGXMZMX]ERHWIRWSV]JYRGXMSR# MMM,S[MWWIRWSV]MRJSVQEXMSRIRGSHIHERHMRXIKVEXIHF] MRHMZMHYEPGIPPWERHW]RETWIW# Publications %RKIPS/6ERG^)%4MQIRXIP(,YRHELP',ERRMFEP. *PIMWGLQERR%4MGLPIV&ERH1EVKVMI8; %FMSTL]WMGEPWMKREXYVISJRIX[SVOEJ½PMEXMSRERHWIRWSV] processing in mitral cells. Nature 488¯ 6ERG^)%*VEROW/17GL[EV^1/4MGLPIV&7GLEIJIV%8ERH 1EVKVMI8; Transfection via whole-cell recording in vivo: bridging singlecell physiology, genetics and connectomics. Nature Neuroscience 14 'LEHHIVXSR4%KETMSY.41G%PTMRI(ERH1EVKVMI8; The synaptic representation of sound source location in auditory cortex. Journal of Neuroscience 29 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR In vivo optical imaging of odor-evoked glomerular activity in the mammalian olfactory bulb. Each KPSQIVYPYWVIHGMVGPIGSRXEMRWTVMRGMTEPQMXVEPGIPPW[MXLRIX[SVOWTIGM½GLSQSX]TMG biophysical properties. MRC National Institute for Medical Research 81 NEUROSCIENCES Molecular Neurobiology Vassilis Pachnis Development of the nervous system 0EFQIQFIVW;IVIRH&SIWQERW1]VXS(IRE\E8MJJER],IERYI1IPERMI/EPEMX^MHSY4ERE]SXMW/EFSYVMHMW 'LV]WWE/SRWXERXMRMHSY6IIRE0EWVEHS6MXE0STIW7EVEL1G'EPPYQ:EPIRXMRE7EWWIPPM 8LIRIVZSYWW]WXIQMWGVMXMGEPJSVXLIMRXIVEGXMSRSJSVKERMWQW [MXLXLIMVIRZMVSRQIRXGSRXVMFYXIWXSXLIQEMRXIRERGISJ MRXIVREPLSQISWXEWMWERHMWXLIEREXSQMGEPWYFWXVEXISJGSKRMXMZI EGXMZMX]2SVQEPJYRGXMSRSJXLIRIVZSYWW]WXIQHITIRHWSR XLIKIRIVEXMSREXXLIVMKLXXMQIERHTPEGISJMRXIKVEXIHGIPPYPEV RIX[SVOWQEHIYTSJEPEVKIRYQFIVSJHMZIVWIRIYVSRW 9RHIVWXERHMRKXLIQIGLERMWQWXLEXGSRXVSPXLIKIRIVEXMSRSJ HMWXMRGXRIYVSREPWYFX]TIWERHXLIMVQMKVEXMSRXSXLIETTVSTVMEXI PSGEXMSRMWGVMXMGEPJSVGSQTVILIRHMRKRSVQEPRIYVSREP HIZIPSTQIRXERHJSVXVIEXMRKRIYVSREPHI½GMIRGMIW 3YVWXYHMIWI\TPSVIXLIQIGLERMWQWXLEXGSRXVSPXLI HIZIPSTQIRXSJXLIIRXIVMGRIVZSYWW]WXIQMRXLIKYX LS[IRXIVMGRIYVSRWERHXLIMVTVSKIRMXSVWQMKVEXIHYVMRK IQFV]SKIRIWMWERHLS[XLI]HMJJIVIRXMEXIXSJSVQGSQTPI\ RIX[SVOWXLEXVIKYPEXIKYXQSXMPMX]ERHWIGVIXMSRW;IEPWS WXYH]XLIQIGLERMWQWXLEXGSRXVSPRIYVSREPHMJJIVIRXMEXMSR MRXLIJSVIFVEMR;ILEZIMHIRXM½IHWMKREPWXLEXQIHMEXI GIPPYPEVMRXIVEGXMSRWQSPIGYPIWXLEXYRHIVPMIXLIJYRGXMSREP MRXIVGSRRIGXMSRSJRIYVSRWERHXVERWGVMTXMSRJEGXSVWYRHIVP]MRK RIYVSREPGIPPJEXIHIGMWMSRW3YVWXYHMIWTVSZMHIRSZIPMRWMKLXMRXS XLIHIZIPSTQIRXERHJYRGXMSRSJXLIRIVZSYWW]WXIQMRRSVQEP ERHHMWIEWIGSRHMXMSRW Publications (IRE\E1/EPEMX^MHSY1+EVIJEPEOM%%GLMQEWXSY% 0EWVEHS61EIW8ERH4EGLRMW: Maturation promoting activity of Satb1 in MGEderived cortical interneurons. Cell Reports Vol 2 0EVERNIMVE' 7ERHKVIR/ /IWWEVMW2 6MGLEVHWSR; 4SXSGRMO%:ERHIR&IVKLI4ERH4EGLRMW: Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury. Journal of Clinical Investigation 121 /MSYWWMW(ERH4EGLRMW: Immune and nervous systems: more than just a WYTIV½GMEPWMQMPEVMX]# Immunity 31 7IIVIJIVIRGIWERHMR XLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR A rich neuronal network within the outer wall (bottom) and the villi (top) of adult intestine. 82 MRC National Institute for Medical Research Maturation of different classes of interneuron precursors transplanted into the cortex of postnatal mice. NEUROSCIENCES Molecular Neurobiology Iris Salecker Visual circuit assembly in Drosophila 0EFQIQFIVW,SPKIV%TMX^(EJRM,EHNMIGSRSQSY&IRNEQMR6MGLMIV2ERE7LMQSWEOS 8LIEFMPMX]SJERMQEPWXSTIVJSVQXLIQER]XEWOWSJXLIMV IZIV]HE]PMZIWVIPMIWSRXLITIVJIGXJYRGXMSRMRKSJXLIMVFVEMRW 8LIWIGSRWMWXSJHMZIVWIRIYVSRERHKPMEPWYFX]TIW;MXLMR WTIGM½GFVEMREVIEWRIYVMXIWEVISVKERMWIHMRXSVIMXIVEXIH GSPYQREVERHPE]IVIHW]RETXMGYRMXW8LIQSPIGYPEVQIGLERMWQW XLEXGSRXVSPXLIJSVQEXMSRSJXLIWIHMJJIVIRXGIPPX]TIWERHXLIMV EWWIQFP]MRXSJYRGXMSREPRIYVEPRIX[SVOWHYVMRKHIZIPSTQIRX VIQEMRTSSVP]YRHIVWXSSH8SEHHVIWWXLIWIMWWYIW[IYWIXLI ZMWYEPW]WXIQSJDrosophilaFIGEYWIMXIREFPIWYWXSHMWWIGXXLI WXIT[MWIHIZIPSTQIRXSJEGSQTPI\RIYVEPGMVGYMX[MXLKIRIXMG ETTVSEGLIWERHWMRKPIGIPPVIWSPYXMSR 3RIPMRISJSYVVIWIEVGLMRZIWXMKEXIWXLIQIGLERMWQWXLEX GSRXVSPXLIJSVQEXMSRSJPEQMREXIHGMVGYMXW-RTEVXMGYPEV [IJSGYWSRXLIXEVKIXMRKWXITWSJXLIGSPSYVWIRWMXMZI TLSXSVIGITXSVE\SRWYFX]TI6XSMXWXIQTSVEV]ERH½REP W]RETXMGPE]IVW3YVVIGIRXWXYH]SJ2IXVMRWERHXLIMVVIGITXSV *VE^^PIHXLI¾]LSQSPSKSJZIVXIFVEXI(IPIXIHMR'SPSVIGXEP 'ERGIV(''EHHIHEHMWXMRGXQIGLERMWQXSXLII\MWXMRK GSRGITXWSJPE]IVWTIGM½GXEVKIXMRK;IHIQSRWXVEXIHXLEX TVSZMWMSRSJEPSGEPMWIHWLSVXVERKIGLIQSEXXVEGXERXF] MRXIVQIHMEXIXEVKIXRIYVSRWVITVIWIRXWELMKLP]TVIGMWIWXVEXIK] XSHMVIGXEJJIVIRXE\SRW[LMGLWTIGM½GEPP]I\TVIWWXLIVIGITXSV XSEWMRKPITSWMXMSREPP]HI½RIHXEVKIXPE]IV Publications 3]EPPSR.%TMX^,1MKYIP%PMEKE- 8MQSJIIZ/*IVVIMVE0ERH7EPIGOIV - Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors. Developmental Biology 369 8MQSJIIZ/.SP];,EHNMIGSRSQSY( ERH7EPIGOIV- Localized Netrins act as positional GYIWXSGSRXVSPPE]IVWTIGM½G targeting of photoreceptor axons in Drosophila Neuron 75 ,EHNMIGSRSQSY(6SXOSTJ7 %PI\ERHVI'&IPP(1(MGOWSR&.ERH 7EPIGOIV- Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster. Nature Methods 8 Adult Drosophila visual system: R8 axons (blue) terminate in the medulla layer M3. Netrin-B releasing neurons, visualised with the Flybow approach, include lamina neurons L3, which innervate the same layer. Visual system during mid pupal development: Netrin-B TVSXIMRFPYIMWWTIGM½GEPP]PSGEPMWIHMRXLIQIHYPPE neuropil layer M3, where R8 photoreceptor axons terminate (red, arrow in inset). MRC National Institute for Medical Research 83 NEUROSCIENCES Developmental Neurobiology David Wilkinson Regulation of boundary formation and neurogenesis 0EFQIQFIVW1EVMI&VIEY%RKIPE'LIYRK7IER'SRWXEFPI%RHVI[+ISVKMSY1SLEQIH-WQEMP6SWEPMRH1SVPI]%PI\IM4SPMEOSZ ,EVVMIX8E]PSV5MPMRK<Y 8LIJSVQEXMSRSJEWLEVTFSYRHEV]FIX[IIREHNEGIRXVIKMSRW MWMQTSVXERXJSVIWXEFPMWLMRKXLIGSVVIGXSVKERMWEXMSRSJXMWWYIW ERH[LIRHMWVYTXIHYRHIVPMIWHMWIEWIWYGLEWXLIQIXEWXEXMG WTVIEHMRKSJGERGIVGIPPW-RXLIZIVXIFVEXIRIVZSYWW]WXIQWTIGM½G FSYRHEVMIWLEZIEGVYGMEPVSPIMRXLIVIKYPEXMSRSJRIYVSREP HMJJIVIRXMEXMSR3YVWXYHMIWJSGYWSRXLIZIVXIFVEXILMRHFVEMREW EQSHIPXSEHHVIWWXLVIIMRXIVPMROIHUYIWXMSRWLS[FSYRHEVMIW JSVQ[LEXXLIMVVSPIWEVIERHLS[RIYVSKIRIWMWMWVIKYPEXIH ;IYXMPMWIin vitroEWWE]Win vivoJYRGXMSREPWXYHMIWERHGSQTYXIV QSHIPPMRKXSYRHIVWXERHLS[WMKREPPMRKXLVSYKL)TLVIGITXSVW ERHITLVMRWYRHIVPMIWXLIJSVQEXMSRSJWLEVTFSVHIVW-RVIPEXIH [SVO[IWXYH]LS[LMRHFVEMRFSYRHEVMIWMRGSPPEFSVEXMSR[MXL WMKREPPMRKJVSQWTIGM½GRIYVSRWSVKERMWIHMWGVIXI^SRIWSJRIYVSREP HMJJIVIRXMEXMSR[MXLMRWIKQIRXW*MREPP][IEVIHMWWIGXMRKER MRXVEGIPPYPEVRIX[SVOXLEXVIKYPEXIWRIYVEPWXIQGIPPQEMRXIRERGI ERHXLISRWIXSJRIYVSREPHMJJIVIRXMEXMSR8LIWIWXYHMIWYXMPMWIXLI TS[IVJYPKIRIXMGERHXVERWKIRMGXSSPWEZEMPEFPIMR^IFVE½WLJSVXLI EREP]WMWSJKIRIJYRGXMSRERHin vivoMQEKMRKSJGIPPFILEZMSYV 7IKQIRXEPSVKERMWEXMSRSJRIYVSRWMRXLI^IFVE½WLLMRHFVEMRRIYVSRW green; progenitors, red). Our studies have revealed a link between XLITSWMXMSRMRKSJWTIGM½GRIYVSRWERHXLIHMJJIVIRXMEXMSRSJRIYVEP progenitors. Publications &EXPPI)ERH;MPOMRWSR(+ Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis. Cold Spring Harbor Perspectives in Biology 4E 8IVVMIRXI.+IVIX]77;EXEREFI%WEOE8+SR^EPI^5YIZIHS6ERH;MPOMRWSR(+ Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis. Development 139 +SR^EPI^5YIZIHS60II=4SWW/(ERH;MPOMRWSR(+ Neuronal regulation of the spatial patterning of neurogenesis. Developmental Cell 18 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRW JVSQXLMWKVSYTMR 84 MRC National Institute for Medical Research Still from time lapse movie of the developing hindbrain in a XVERWKIRMG^IFVE½WLPMRI8LMWPMRIIREFPIWQSWEMGPEFIPPMRKSJ cells (green) and visualisation of hindbrain segments (red). Genetics and Development Developmental Biology James Briscoe (Joint Head of Division) Jean-Paul Vincent (Joint Head of Division) Malcolm Logan Tim Mohun Andrew Oates Elke Ober Lyle Zimmerman Stem Cell Biology and Developmental Genetics Robin Lovell-Badge (Head of Division) Paul Burgoyne Peter Thorpe James Turner Systems Biology Jim Smith (Head of Division) Greg Elgar Mike Gilchrist MRC National Institute for Medical Research 85 GENETICS AND DEVELOPMENT Developmental Biology James Briscoe Pattern formation in the vertebrate nervous system 0EFQIQFIVW6SFIVX&PEWWFIVK1MGLEIP'SLIR/EXVMRE+VMJ½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½GEPP][IEVIMRXIVIWXIHMRXLIGIPPYPEVERHQSPIGYPEVQIGLERMWQWVIWTSRWMFPI JSVTEXXIVRJSVQEXMSRMRXLIRIYVEPXYFI-RZIRXVEPVIKMSRWSJXLIGEYHEPRIYVEPXYFI XLIWIGVIXIHQSPIGYPI7SRMG,IHKILSK7LLJSVQWERI\XVEGIPPYPEVKVEHMIRXXLEX KSZIVRWTEXXIVRJSVQEXMSRERHXMWWYIKVS[XL;IYWIEVERKISJQSPIGYPEVMQEKMRKERH QSHIPPMRKETTVSEGLIWXSMHIRXMJ]ERHVIGSRWXVYGXXLIVIKYPEXSV]RIX[SVOXLEXGSRXVSPW XLIKVS[XLERHHIZIPSTQIRXSJXLIZIRXVEPRIYVEPXYFI Publications &EPEWOEW26MFIMVS%4ERSZWOE.(IWWEYH)7EWEM2 4EKI/EVIR1&VMWGSI.ERH6MFIW: Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell 148 (IWWEYH)6MFIW:&EPEWOEW2=ERK004MIVERM% /MGLIZE%2SZMXGL&+&VMWGSI.ERH7EWEM2 Dynamic assignment and maintenance of positional identity in the ventral neural tube by the morphogen Sonic hedgehog. PLOS Biology 8I 8LIGSQFMREXSVMEPTEXXIVRSJKIRII\TVIWWMSRHI½RIHMWXMRGXHSQEMRWSJTVSKIRMXSVWMRXLIRIYVEPXYFI 6MFIW:&EPEWOEW27EWEM2'VY^'(IWWEYH) 'E]YWS.8S^IV7=ERK002SZMXGL&1EVXM)ERH &VMWGSI. Distinct Sonic Hedgehog signaling dynamics specify ¾SSVTPEXIERHZIRXVEPRIYVSREPTVSKIRMXSVWMRXLI vertebrate neural tube. Genes & Development 24 7IIVIJIVIRGIWERH MRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRW JVSQXLMWKVSYTMR 86 MRC MRCNational NationalInstitute InstituteforforMedical MedicalResearch Research The dynamics of a gene regulatory network controlled by Shh/Gli activity progressively establish gene expression domains in the neural tube. GENETICS AND DEVELOPMENT Stem Cell Biology and Developmental Genetics Paul Burgoyne The Y chromosome and infertility 0EFQIQFIVW*ERR](IGEVTIRXVMI7LERXLE1ELEHIZEMEL3FEL3NEVMOVIÅMRI6EXXMKER2EHIKI:IVRIX 8LI½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½GMIRXXSI\TPEMRXLIRIEVWXIVMPMX]SJ<=JIQEPIW [MXLEOFHIPIXMSRVIQSZMRK7V]EWGSQTEVIHXSXLIJIVXMPMX]SJ<=HJIQEPIWXLEX LEZIEQYGLPEVKIVHIPIXMSREWWSGMEXIH[MXLXLIXVERWGVMTXMSREPWMPIRGMRKSJ7V]ERHXLI VITVIWWMSRSJ>J] Publications 'SGUYIX.)PPMW4.-1ELEHIZEMEL7/%JJEVE2%:EMQER(ERH &YVKS]RI47 A genetic basis for a postmeiotic X versus Y chromosome MRXVEKIRSQMGGSR¾MGXMRXLIQSYWI PLOS Genetics 8I :IVRIX21ELEHIZEMEL7/)PPMW4.HI6SSMN(+ERH &YVKS]RI47 Spermatid development in XO male mice with varying Y chromosome short arm gene content: evidence for a Y gene controlling the initiation of sperm morphogenesis. Reproduction 144 XYd female mice are much more fertile than XYSry- females. It was hypothesised that this was due to the much reduced ovarian expression of Rbmy in females with the Yd deletion. :IVRIX21ELEHIZEMEL7/3NEVMOVI3%0SRKITMIH+ 4VSWWIV,1&VEHPI]%1MXGLIPP1.ERH&YVKS]RI47 The Y-encoded gene Zfy2 acts to remove cells with YRTEMVIHGLVSQSWSQIWEXXLI½VWXQIMSXMGQIXETLEWIMR male mice. Current Biology 21 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EX XLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 87 GENETICS AND DEVELOPMENT Systems Biology Greg Elgar Regulation of early vertebrate development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½WLIQFV]SWERMQTSVXERXERH XVEGXEFPIQSHIPJSVXLMWWSVXSJ[SVO3RGI[IMHIRXMJ]WTIGM½G VIKYPEXSV]TEXXIVRW[IGERWIEVGLJSVXLIWIXLVSYKLSYXXLI KIRSQIXLIVIF]TVIHMGXMRKSXLIVVIKYPEXSV]VIKMSRW-XMWMQTSVXERX XLEX[IORS[[LIVIXLIWIVIKMSRWEVIMRXLIKIRSQIERH [LEXTVSGIWWIWXLI]HI½RIEWQYXEXMSRWMRXLIQGERPIEHXS HIZIPSTQIRXEPHMWSVHIVWERHKIRIXMGHMWIEWI 0MZI¾YSVIWGIRXMQEKMRKSJIRLERGIVEGXMZMX]MR^IFVE½WL embryos, articulating reporter expression in midbrain and hindbrain. Publications 4EYPW77QMXL7*ERH)PKEV+ Lens development depends on a pair of highly conserved Sox21 regulatory elements. Developmental Biology 365 +SSHI(/'EPPE[E],%'IVHE+%0I[MW/)ERH)PKEV+ Minor change, major difference: divergent functions of highly conserved cis-regulatory elements subsequent to whole genome duplication events. Development 138 4EVOIV,.4MGGMRIPPM47EYOE7TIRKPIV8&VSRRIV1ERH)PKEV + %RGMIRX4F\,S\WMKREXYVIWHI½RILYRHVIHWSJZIVXIFVEXI developmental enhancers. BMC Genomics 12 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 88 MRC National Institute for Medical Research Building networks of relationships between binding motifs in regulatory elements. GENETICS AND DEVELOPMENT Systems Biology Mike Gilchrist Gene regulatory networks in early development 0EFQIQFIVW&VSSO'SSTIV-ER+VERX2MGO3[IRW-P]E4EXVYWLIZ )QFV]SHIZIPSTQIRXMWEGSQTPI\ERHXMKLXP]GSRXVSPPIHTVSGIWW[MXLE VIQEVOEFP]TVIGMWISYXGSQI8]TMGEPP]XVERWGVMTXMSRJEGXSVWVIKYPEXIXLI I\TVIWWMSRSJMRHMZMHYEPKIRIWXLVSYKLGSQTPI\KIRIVIKYPEXSV]RIX[SVOW 3YVEMQMWXSIPYGMHEXIXLIWIRIX[SVOWYWMRKQSPIGYPEVERHGSQTYXEXMSREP XSSPWXLEXIREFPIEW]WXIQEXMGERHPEVKIWGEPIETTVSEGL3YV½VWXWXITWMRXLMW HMVIGXMSRLEZIFIIRXSQETSYXXLIXIQTSVEPPERHWGETISJKIRIEGXMZEXMSRMR XLIIEVP]IQFV]S %JXIVJIVXMPMWEXMSRXLI½VWXQENSVIZIRXMRXLIIQFV]S´WPMJIMWXLIQMHFPEWXYPE XVERWMXMSR1&8[LIRXLIKIRSQIFIGSQIWXVERWGVMTXMSREPP]EGXMZI'SRXVSP EXXLIQSPIGYPEVPIZIPRS[TEWWIWJVSQQEXIVREPKIRITVSHYGXWXSXLSWI HIVMZIHJVSQXLIIQFV]S´WS[RKIRIWERHHIZIPSTQIRXVETMHP]FIGSQIW EW]RGLVSRSYWERHQSVIGSQTPI\8LITVIGMWIXMQMRKERHI\XIRXSJXLMW XVERWMXMSRMWRSX[IPPHI½RIHERHQER]OI]KIRIWEVIPMOIP]YRMHIRXM½IH8S I\TPSVIMX[ILEZIGVIEXIHELMKLVIWSPYXMSRXMQIWIVMIWSJTSP]%Q62% WEQTPIWJVSQXenopus tropicalisIQFV]SWGSZIVMRKXLI½VWXXIRLSYVWSJ HIZIPSTQIRX[MXL1&8EXEFSYXLSYVW8LIWEQTPIW[IVIWIUYIRGIHXS GVIEXIKIRII\TVIWWMSRTVS½PIW[LMGL[ILEZIWYFWIUYIRXP]EREP]WIHJSV WMKREPWSJKIRIEGXMZEXMSR8LMWXIPPWYW[LMGLKIRIWEVIEGXMZEXIHEX1&8ERH MR[LEXSVHIV Publications +MPGLVMWX1. From expression cloning to gene modeling: the development of Xenopus gene sequence resources. genesis 50 +VERX.1ELEHIZEMEL7//LMP47ERKVMXLM126S]S,(YGO[SVXL. 1G'EVVI].6:ERHI&IVK.06IRJVII1&8E]PSV;)PKEV+'EQIVMRM3XIVS 6(+MPGLVMWX1.ERH8YVRIV.1 Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature 4879 7MQISRM-+MPGLVMWX1.+EVVIXX2%VQMWIR.ERH+YVHSR.& Widespread transcription in an amphibian oocyte relates to its reprogramming activity on transplanted somatic nuclei. Stem Cells and Development 21 ,MKLVIWSPYXMSRKIRII\TVIWWMSRTVS½PIWKIRIVEXIHJVSQ-PPYQMRE62%WIUHEXE through the mid-blastula transition in Xenopus tropicalis. Chart shows data for Wnt signaling genes, with clear signals of transcriptional activation for two of them. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 89 GENETICS AND DEVELOPMENT Developmental Biology Malcolm Logan Understanding vertebrate limb development 0EFQIQFIVW0EYVMERRI&IWWI7SVVIP&MGOPI]2EXEPMI&YJJIV½IPH1EVXMR'EVOIXX:IVSRMUYI(YFSG%RRE/YGLEVWOE 7YI1MPPIV7EXSOS2MWLMQSXS 0MQFHIJIGXWEVIEGSQQSRGSRKIRMXEPEFRSVQEPMX]TVIWIRX MRLYQERPMZIFMVXLWERHHMWIEWIWEJJIGXMRKXLIQYWGYPSWOIPIXEP W]WXIQEVIEWMKRM½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in vitroQSHIPWERHEGSQFMREXMSRSJ KIRIXMGWMQEKMRKERHFMSMRJSVQEXMGWETTVSEGLIWXSYRHIVWXERHXLI QIGLERMWQWXLEXGSRXVSPPMQFFYHJSVQEXMSRERHXLIWYFWIUYIRX GSRWXVYGXMSRSJXLIMRHMZMHYEPPMQFIPIQIRXW Publications 1MRKYMPPSR'2MWLMQSXS7;SSH7:IRHVIPP)+MFWSR&VS[R ..ERH0SKER143 Hox genes regulate the onset of Tbx5 expression in the forelimb. Development 139 (YFSG:ERH0SKER143 Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control. Development 138 ,EWWSR4(I0EYVMIV%&IRRIXX1+VMKSVMIZE)2EMGLI0% 4ETEMSERRSY:)1SLYR8.ERH0SKER143 Tbx4 and Tbx5 acting in connective tissue are required for limb muscle and tendon patterning. Developmental Cell 18 Embryonic day 10.5 mouse forelimb bud showing staining of dpERK (green) and cell nuclei with DAPI (blue). 90 MRC National Institute for Medical Research Embryonic day 13.5 forelimb showing developing HMKMXWSJXLILERHTPEXIMHIRXM½IH[MXLE'SPP+*4 transgene (green) and cells in G1 of the cell cycle (red) using the FUCCI transgene. GENETICS AND DEVELOPMENT Stem Cell Biology and Developmental Genetics Robin Lovell-Badge FRS, EMBO member, FMedSci Sex, stem cells and decisions of cell fate 0EFQIQFIVW7EVEL&SSXL'LVMWXSTLI+EPMGLIX7EQ+SPHWQMXL2MX^ER+SRIR7MPZERE+YMSPM,IPIR3´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ublications +zQI^+EZMVS1:7GSXX') 7IWE]%/1EXLIY%&SSXL7 +EPMGLIX'ERH0SZIPP&EHKI6 Betacellulin promotes cell proliferation in the neural stem cell niche and stimulates neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 109 Compared to controls, BTC null mutant mice are less able to regenerate (PSA-NCAM+ve) neuroblasts from (SOX2+ve) neural stem cells in the SVZ niche 6 days after treatment with Ara-C, a drug that kills Ki67+ve dividing cells. From Gomez-Gaviro et al, 2012. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL] EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR 7YXXSR),YKLIW.;LMXI7 7IOMHS68ER.%VFSPIHE: 6SKIVW2/RS[IV/6S[PI]0 )]VI,6M^^SXM/1G%RMRGL( +SRGEPZIW.7PII.8YVFMXX)&VYRS (&IRKXWWSR,,EVPI]::MPEMR )7MRGPEMV%0SZIPP&EHKI6ERH 8LSQEW4 -HIRXM½GEXMSRSJ73<EWER<< male sex reversal gene in mice and humans. Journal of Clinical Investigation 121 A sex-reversing Sox3 transgene mimics Sry and not Sox9. This explains how Sry could have evolved from Sox3 via a regulatory mutation, and why rearrangements of the X chromosome near SOX3 are associated with human XX male sex reversal. From Sutton et al, 2011 7GSXX');]RR707IWE]% 'VY^''LIYRK1 +EZMVS1:+&SSXL7+ES& 'LIEL/7)0SZIPP&EHKI6ERH &VMWGSI. SOX9 induces and maintains neural stem cells. Nature Neuroscience 13¯ MRC National Institute for Medical Research 91 GENETICS AND DEVELOPMENT Developmental Biology Tim Mohun Heart development in vertebrates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n this tadpole, muscle cells of the heart, head and body can be readily ZMWYEPMWIHXLVSYKLI\TVIWWMSRSJE¾YSVIWGIRXVITSVXIVTVSZMHMRKEWMQTPI way to monitor heart development. Publications 7QMXL7.ERH1SLYR8. Early cardiac morphogenesis defects caused by loss of embryonic macrophage function in Xenopus. Mechanisms of Development 128 (YRPIZ]0&IRRIXX17PIRHIV%0ERE)PSPE)8]FYPI[MG^:0*MWLIV)1'ERH1SLYR8 Down’s syndrome-like cardiac developmental defects in embryos of the transchromosomic Tc1 mouse. Cardiovascular Research 88 3D models of the mouse embryo heart (left) or the lumens of the heart GLEQFIVWVMKLXVIZIEPXLIGSQTPI\QIWLSJQYWGPI½FVIWGLEVEGXIVMWXMGSJ the embryonic heart. (YTE]W0/SXIGLE7ERH1SLYR8. 8F\QMWI\TVIWWMSRMQTEMVWHITPS]QIRXSJWIGSRHLIEVX½IPHHIVMZIHTVSKIRMXSVGIPPWXSXLI arterial pole of the embryonic heart. Developmental Biology 333 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSV TYFPMGEXMSRWJVSQXLMWKVSYTMR 92 MRC National Institute for Medical Research GENETICS AND DEVELOPMENT Developmental Biology Andrew Oates Patterning embryos with oscillations 0EFQIQFIVW0SPE&ENEVH6EZM(IWEM'LVMWXMRE)YKWXIV'PEYHME*V}F(EZMH.}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½IHXLI½VWXQYXEXMSRWXLEXGLERKIXLIWIKQIRXEXMSRGPSGO´WTIVMSHSTIRMRKXLIHSSVXS QSPIGYPEVYRHIVWXERHMRKSJXLIQIGLERMWQWXLEXGSRXVSPXLIGPSGO´WH]REQMGW;IEVIFIKMRRMRKXSI\TPSVIRI[XVERWKIRMGXSSPW XSJSPPS[XLISWGMPPEXMSRWSJXLIWIKQIRXEXMSRGPSGOMRVIEPXMQI Oscillating gene expression in the segmentation clock can be JSPPS[IHMRPMZI^IFVE½WL embryos at tissue and single cell levels, as well as in vitro. Publications 7GLV}XIV'%VIW71SVIPPM0+-WEOSZE%,IRW/7SVSPHSRM(+ENI[WOM1.YPMGLIV*1EIVOP7.(ITPERGOI& ERH3EXIW%' 8STSPSK]ERHH]REQMGWSJXLI^IFVE½WLWIKQIRXEXMSRGPSGOGSVIGMVGYMX PLOS Biology 10:e1001364 ,IVVKIR07GLV}XIV'1SVVIPM0%VIW7.YPMGLIV*ERH3EXIW%' Intercellular coupling regulates the period of the segmentation clock. Current Biology 20 6MIHIP/VYWI-,1PPIV'3EXIW%' Synchrony dynamics during initiation, failure, and rescue of the segmentation clock. Science 317 The three-tier model of the vertebrate segmentation clock, a rhythmic, tissue-level pattern generator responsible for sequential formation of the embryonic segments that give rise to backbone, ribs and associated muscles. MRC National Institute for Medical Research 93 GENETICS AND DEVELOPMENT Developmental Biology Elke Ober 0MZIVHIZIPSTQIRXMR^IFVE½WL 0EFQIQFIVW.SLERRE*MWGLIV.SVHM'E]YWS1EW(IWTMRE7XEQEXEOM 8LIPMZIVMWXLIPEVKIWXSVKERMRXLIZIVXIFVEXIFSH]TIVJSVQMRK RYQIVSYWIWWIRXMEPTL]WMSPSKMGEPERHQIXEFSPMGVSPIWXSQEMRXEMR FSH]LSQISWXEWMW%WERSVKEREGGIWWSV]XSXLIEPMQIRXEV] GEREPXLIPMZIVHIZIPSTWMRGPSWITVS\MQMX]XSXLIPYRKTERGVIEW ERHWXSQEGL[LMGLJYP½PWMQMPEVP]WTIGMEPMWIHERHZMXEPJYRGXMSRW 8LMWVEMWIWXLIMQTSVXERXUYIWXMSRWLS[XLIKIRIVEXMSRSJXLIWI HMZIVWISVKERWMWGSRXVSPPIHERH[LMGLQIGLERMWQWHIXIVQMRI XLIMVETTVSTVMEXIWLETIERHWM^I8LIMHIRXM½GEXMSRSJSVKER WTIGM½GKIRIXMGTVSKVEQQIW[MPPTVSZMHIMRWMKLXWRSXSRP]MRXSXLI QIGLERMWQWVIKYPEXMRKIQFV]SRMGHIZIPSTQIRXFYXEPWSXMWWYI LSQISWXEWMWERHVIKIRIVEXMSRJSPPS[MRKMRNYV]MREHYPXW 0MZIVTVSKIRMXSVWXLILITEXSFPEWXWEVIWTIGM½IHJVSQXLI QYPXMTSXIRXJSVIKYXIRHSHIVQ8LMWIRGSQTEWWIWEX[SWXIT TVSGIWWMR[LMGLXLIIRHSHIVQ½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½WL[MXLLMKLVIWSPYXMSRMQEKMRK Publications 4SYPEMR1ERH3FIV)% Interplay between Wnt2 and Wnt2bb controls multiple steps of early foregut-derived organ development. Development 138 2StP)7HSW6IMW1%VEMR>ERH3FIV)% Analysis of the albumin_JIXSTVSXIMREJEQMRKVSYT WTIGM½G component KIRI JEQMP] MR XLI GSRXI\X SJ ^IFVE½WL PMZIV differentiation. Gene Expression Patterns 10 2StP)7'EWEP7YIMVS%&YWGL2IRX[MGL):IVOEHI,(SRK 4(77XIQTPI(0ERH3FIV)% 3VKERWTIGM½GVIUYMVIQIRXWJSV,HEGMRPMZIVERHTERGVIEW formation. Developmental Biology 322 Transgenic Red Fluorescent Protein highlights the developing liver within the digestive system. 94 MRC National Institute for Medical Research This transgenic line can also drive the mosaic I\TVIWWMSRSJQIQFVERIXEVKIXIH¾YSVIWGIRX proteins (white) to reveal the cell shapes and arrangement during liver morphogenesis. GENETICS AND DEVELOPMENT Systems Biology Jim Smith FRS, EMBO member, FMedSci The molecular basis of mesoderm formation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½WLERHQSYWIIQFV]SWEW[IPPEW )7GIPPWXSWXYH]QIWSHIVQMRHYGMRKJEGXSVWERHXSEWO LS[GIPPWVIWTSRHXSXLIQ-RTEVXMGYPEV[IYWIMQEKMRK ETTVSEGLIWXSYRHIVWXERHLS[XLIWMKREPWI\IVXPSRKVERKI IJJIGXWERHFMSGLIQMGEPERHQEXLIQEXMGEPETTVSEGLIWXS EWOLS[GIPPWHMWXMRKYMWLFIX[IIRHMJJIVIRXQSVTLSKIR GSRGIRXVEXMSRW;IEPWSYWIWSTLMWXMGEXIHQSPIGYPEV XIGLRMUYIWXSIPYGMHEXIXLIKIRIXMGVIKYPEXSV]RIX[SVOW XLEXHVMZIXLIJSVQEXMSRSJWTIGM½GGIPPX]TIWMRQIWSHIVQ MRGPYHMRKZEWGYPEVGIPPWERHRIYVEPGVIWX%W[IPPEWLIPTMRK YRHIVWXERHHIZIPSTQIRXSYV[SVO[MPPEWWMWXMRIJJSVXWXS HMVIGXWXIQGIPPWHS[RHIWMVIHHIZIPSTQIRXEPTEXL[E]W Publications 'EPPIV])14EVO'=<Y<>LY,7QMXL.'ERH8LSQWIR +, Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins. Open Biology 2 )ZERW%0*EMEP8+MPGLVMWX1.(S[R8:EPPMIV04IHIVWIR6% ;EVHPI*'ERH7QMXL.' Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells. PLOS ONE 7:e33346 'SPPEVX''LVMWXSZ'47QMXL.'ERH/VYHI8 8LIQMHFPEWXYPEXVERWMXMSRHI½RIWXLISRWIXSJ=62% dependent DNA replication in Xenopus laevis. Molecular and Cellular Biology 31¯ (IZIPSTQIRXSJXLI^IFVE½WLGEYHEP venous plexus requires BMP signalling and FPSSH¾S[8VIEXQIRX[MXL&14MRLMFMXSV LDN193189 or knockdown of cardiac troponin T2a (tnnt2a) causes defects in plexus formation. Top: Fluorescent neural crest cells migrate into the branchial arches of a Xenopus embryo. Bottom: Sox10 promoter drives ¾YSVIWGIRXTVSXIMRI\TVIWWMSRMRRIYVEP GVIWXERHTPEGSHIWSJE^IFVE½WLIQFV]S MRC National Institute for Medical Research 95 GENETICS AND DEVELOPMENT Stem Cell Biology and Developmental Genetics Peter Thorpe Systems microscopy studies of cell fate determination 0EFQIQFIVW)ZE,IVVIVS)PIRE0IHIWQEERH+YëNzRÌPEJWWSR %W]QQIXVMGGIPPHMZMWMSRMWXLITVSGIWWF][LMGLSRIGIPP HMZMHIWXSKMZIX[SGIPPW[MXLHMJJIVIRXJEXIW6ITIEXIH EW]QQIXVMGHMZMWMSRWEPPS[EJIVXMPMWIHIKKXSKIRIVEXI HMZIVWIGIPPX]TIWHYVMRKHIZIPSTQIRXERHMREHYPX WXIQGIPPWWYGLHMZMWMSRWQEMRXEMRXLITSTYPEXMSR[LMPI WMQYPXERISYWP]KIRIVEXMRKRI[HMJJIVIRXMEXIHGIPPW 8LIKSEPSJSYVKVSYTMWXSHIXIVQMRILS[GIPPYPEV EW]QQIXV]MWIWXEFPMWLIHERHQEMRXEMRIHSZIVQYPXMTPI HMZMWMSRWXSGVIEXIGIPPPMRIEKIW7TIGM½GEPP][IJSGYWSR YRHIVWXERHMRKLS[EW]QQIXV]SJXLIQMXSXMGWTMRHPI XLIQEGLMRIV]XLEXWIKVIKEXIWGLVSQSWSQIWHYVMRK HMZMWMSREJJIGXWLS[KIRIXMGMRJSVQEXMSRMWEGGYVEXIP] TEWWIHHS[RXSHEYKLXIVGIPPW 3YVQSHIPW]WXIQMWXLIFYHHMRK]IEWXSaccharomyces cerevisiae, which shows patterns of asymmetric division PMOIXLSWISJQSVIGSQTPI\SVKERMWQW;IIQTPS] LMKLXLVSYKLTYX¾YSVIWGIRGIQMGVSWGST]XIGLRMUYIW XLEXEPPS[YWXSVETMHP]WGVIIRXLIPSGEPMWEXMSRPIZIPWERHH]REQMGWSJEPP]IEWXTVSXIMRWERHMRXIKVEXIXLIQMRXSEZMWYEPHEXEWIX ;IEPWSYWIRSZIPLMKLXLVSYKLTYXKIRSQMGWXIGLRMUYIWXSVIHMVIGXTVSXIMRWXSRI[PSGEXMSRW[MXLMRXLIGIPPERHEWWIWWXLI IJJIGXWYTSRGIPPHMZMWMSR9WMRKXLIWIXSSPW[IEMQXSMHIRXMJ]XLIGSRWIVZIHQIGLERMWQWGSRXVSPPMRKEW]QQIXVMGHMZMWMSRPMRIEKI WTIGM½GEXMSRERHQMXSXMGWTMRHPIJYRGXMSR Publications 8LSVTI4,(MXXQEV.'ERH6SXLWXIMR6 ScreenTroll: a searchable database to compare genomewide yeast screens. Database 2012FEW 8LSVTI4,%PZEVS(0MWF]1ERH6SXLWXIMR6 Bringing Rad52 foci into focus. Journal of Cell Biology 194 8LSVTI4,&VYRS.ERH6SXLWXIMR6 /MRIXSGLSVIEW]QQIXV]HI½RIWEWMRKPI]IEWXPMRIEKI Proceedings of the National Academy of Sciences of the United States of America 106 -RHMZMHYEP]IEWXEVIMHIRXM½IHZMEEGIPPWYVJEGI QEVOIV [LMGL HI½RIW XLI GIPP FSYRHEVMIW Proteins that segregate asymmetrically such EW &JE EVI EYXSQEXMGEPP] MHIRXM½IH ERH XLIMV TSWMXMSRERHMRXIRWMX]UYERXM½IH 96 MRC National Institute for Medical Research High-throughput yeast genomics allows us to test how protein interactions affect cell division. Different protein fusions are arrayed and an MQEKI½PXIVHEVOTERIPEPPS[WZMWYEPMWEXMSRSJ growth impaired strains. 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGO JSVTYFPMGEXMSRWJVSQXLMWKVSYTMR GENETICS AND DEVELOPMENT Stem Cell Biology and Developmental Genetics James Turner X chromosome inactivation, meiotic silencing and infertility 0EFQIQFIVW*ERR](IGEVTIRXVMI)PMEW)PMREXM6YTIVX,YKL;LMXI+V^IKSV^4SPMOMI[MG^1ELIWL7ERKVMXLM(ERMIP7RIPP %PI\;MHKIV -RQEQQEPW<GLVSQSWSQIMREGXMZEXMSR<'-SGGYVWMREPPGIPPW MRXLIJIQEPIERHMRHIZIPSTMRKKIVQGIPPWMRXLIQEPI-RJIQEPIW <'-WIVZIWXSIUYEPMWI<HSWEKI[MXLQEPIW8LIVSPISJ<'-MR QEPIKIVQGIPPWMWYRGPIEV;IWXYH]XLIQIGLERMWQWYRHIVP]MRK FSXLJSVQWSJ<'-ERHXLIMR¾YIRGISJ<'-SRXLIKIRIGSRXIRX SJXLI<GLVSQSWSQI ;ILEZIWLS[RXLEX<'-MRQEPIKIVQGIPPWMWIWWIRXMEPJSVJIVXMPMX] 8LMWWXYH]LEWEPWSEPPS[IHYWXSEWGIVXEMRXLEXQMWI\TVIWWMSRSJ XLIKIRITEMVZfy1/2MWXLIYRHIVP]MRKGEYWISJWXIVMPMX]MR<== QEPIW;ILEZIJSYRHXLEXXLI<GLVSQSWSQIMWLMKLP]IRVMGLIH MRKIRIWMRZSPZIHMRWTIVQHMJJIVIRXMEXMSR[MXLEVSYRHSJ EPPKIRIWSRXLI<GLVSQSWSQIFIMRKI\TVIWWIHSRP]MRQEPI KIVQGIPPW1ER]SJXLIWIKIRIWEVIPMOIP]XSFIMQTSVXERXJSV QEPIJIVXMPMX]-RJIQEPIIYXLIVMERSV³TPEGIRXEP´QEQQEPW<'-MW QIHMEXIHF]XLIRSRGSHMRK62%XistFYXLS[<'-MWGSRXVSPPIH MRXLISXLIVQENSVGPEWWSJQEQQEPWXLIQIXEXLIVMERWLEWFIIR XLIWYFNIGXSJWTIGYPEXMSRJSVHIGEHIW;ILEZIRS[HMWGSZIVIH ERSRGSHMRK62%GEPPIHRsx[LMGLI\LMFMXWJIEXYVIWGSRWMWXIRX [MXLEVSPIMR<'-MRXLIWISVKERMWQW8LMWTEZIWXLI[E]JSV GSQTEVEXMZIWXYHMIWXLEX[MPPEPPS[YWXSFIXXIVYRHIVWXERHLS[ RSRGSHMRK62%WVIKYPEXIKIRII\TVIWWMSR Publications +VERX.1ELEHIZEMEL7//LMP47ERKVMXLM126S]S, (YGO[SVXL.1G'EVVI].6:ERHI&IVK.06IRJVII1&8E]PSV ;)PKEV+'EQIVMRM3XIVS6(+MPGLVMWX1.ERH8YVRIV.1 Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature 4879 6S]S,4SPMOMI[MG^+1ELEHIZEMEL7/4VSWWIV,1MXGLIPP1 &VEHPI]%HI6SSMN(+&YVKS]RI47ERH8YVRIV.1% Evidence that meiotic sex chromosome inactivation is essential for male fertility. Current Biology 20 Expression of Rsx, an RNA that coats and silences the inactive X chromosome (arrow) in the nucleus of female metatherian cells. Rsx RNA coats an autosome in cis (arrowhead) when expressed from a transgene in mouse ES cells. This causes gene silencing, resulting in monoallelic expression of autosomal genes (arrow). 1YIPPIV.01ELEHIZEMEL7/4EVO4.;EVFYVXSR4)4EKI(' ERH8YVRIV.1% The mouse X chromosome is enriched for multicopy testis genes showing postmeiotic expression. Nature Genetics 40 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EX XLIFEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 97 GENETICS AND DEVELOPMENT Developmental Biology Jean-Paul Vincent Patterning and homeostasis in developing epithelia 0EFQIQFIVW']VMPPI%PI\ERHVI0YMW%PFIVXS&EIRE0STI^/EVIR&IGOIXX&I(VYV]'LPSI,YVPMRK7EXSWLM/EOYKE[E4EYP0ERKXSR ,MWEWLM2SNMQE0YG]4EPQIV %WQEPPRYQFIVSJWMKREPPMRKQSPIGYPIWSVGLIWXVEXI KVS[XLERHGIPPJEXIHIGMWMSRWHYVMRKHIZIPSTQIRX ;IMRZIWXMKEXIXLIQIGLERMWQWXLEXGSRXVSPXLI TVSHYGXMSRWTVIEHERHEGXMZMX]SJSRIWMKREP;MRKPIWW EQIQFIVSJXLI;RXJEQMP];IEPWSWXYH]LS[XLI ;MRKPIWWKVEHMIRXGSRXVSPWTEXXIVRMRKERHKVS[XL'IPPW [MXLSZIVEGXMZI;RXWMKREPPMRKIPMQMREXIXLIMVRSVQEP RIMKLFSYVWE½RHMRKXLEXQE]FIVIPIZERXXSXYQSYV FMSPSK]-REWITEVEXIFYXVIPEXIHWXVERHSJVIWIEVGL [IEMQXSYRHIVWXERHXLIQIGLERMWQWXLEXXVMKKIVXLI IPMQMREXMSRSJGIPPWJSPPS[MRKITMXLIPMEPHMWVYTXMSRSVGIPP JEXIQMWWTIGM½GEXMSR (MWVYTXMSRSJITMXLIPMEPGIPPEHLIWMSRPIEHWXS[MHIWTVIEH ETSTXSWMWETLIRSQIRSRXLEXPMOIP]VI¾IGXWXLIRIIH XSIPMQMREXIGIPPWXLEXHIXEGLJVSQXLIITMXLIPMYQXLYW TVIZIRXMRKXLIQJVSQGEYWMRKLEZSG%W[IJSYRH VIGIRXP].YROMREWI.2/MWEOI]QIHMEXSVSJXLMW TVSGIWW,S[IZIVLS[ITMXLIPMEPHMWVYTXMSREGXMZEXIW.2/ VIQEMRWXSFIHMWGSZIVIH-X[MPPEPWSFIMQTSVXERXXS YRHIVWXERH[L]MRSXLIVGIPPYPEVGSRXI\XWXLMWTEXL[E] HSIWRSXRIGIWWEVMP]XVMKKIVETSTXSWMW;IEVIYWMRK XVERWGVMTXMSREPTVS½PMRKGSRJSGEPMQEKMRKERHKIRSQMG IRKMRIIVMRKXSMRZIWXMKEXIXLIPMROWFIX[IIRITMXLIPMEP HMWVYTXMSR.2/WMKREPPMRKERHETSTXSWMW Extensive apoptosis in the segmentation mutant fushi tarazu. Dying cells are marked in red with anti-activated caspase. Publications /SPELKEV+&EVHIX400ERKXSR4*%PI\ERHVI'ERH:MRGIRX.4 %TMGEPHI½GMIRG]XVMKKIVW.2/HITIRHIRXETSTXSWMWMRXLIIQFV]SRMGITMHIVQMWSJ Drosophila. Development 138 :MRGIRX.4/SPELKEV++EKPMEVHM1ERH4MHHMRM) Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Developmental Cell 21 &IGOIXX/1SRMIV74EPQIV0%PI\ERHVI'+VIIR,&SRRIMP)6ETSWS+8LMFEYPX4 &SVKRI60:MRGIRX.4 Drosophila s2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes. 8VEJ½G14 APC mutant cells outcompete neighbouring wild type (wt) cells. Right hand panel shows that the presence of APC mutant cells (not green) leads to the elimination of wt cells (green). 98 MRC National Institute for Medical Research 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLIFEGOJSVTYFPMGEXMSRWJVSQXLMW KVSYTMR GENETICS AND DEVELOPMENT Developmental Biology Lyle Zimmerman Using frog genetics to understand vertebrate development and disease 0EFQIQFIVW%RMXE%FY(E]E8SWMOE^Y%QERS.SEGLMQ/YVXL ,EVZIWXMRKQIHMGEPFIRI½XWJVSQXLILYQERKIRSQIHITIRHWSRYRHIVWXERHMRK XLIXEWOWXLEXWTIGM½GKIRIWTIVJSVQMRPMZMRKSVKERMWQW3YVKVSYTWXYHMIWKIRI JYRGXMSRWMQTSVXERXJSVMRMXMEPJSVQEXMSRSJSVKERWERHWYFWIUYIRXHMWIEWITVSGIWWIW F]MHIRXMJ]MRKERHGLEVEGXIVMWMRKKIRIXMGQYXEXMSRWXLEXTVSJSYRHP]EJJIGXXMWWYI HIZIPSTQIRX7MRGIQSWXKIRIJYRGXMSRWEVIWLEVIHEQSRKEPPZIVXIFVEXIW[IYWIXLI IEWMP]WXYHMIHI\XIVREPP]HIZIPSTMRKIQFV]SWSJEJVSK[MXLEWMQTPIGLVSQSWSQEP WXVYGXYVIXenopus tropicalis ;ILEZITSWMXMSREPP]QETTIHKIRIWYRHIVP]MRKERYQFIVSJQYXEXMSRWMRGPYHMRK WIZIVEPVIWYPXMRKMREFRSVQEPMXMIWSJSXSGSRMEMRRIVIEVGV]WXEPWXVYGXYVIWIWWIRXMEPJSV ZIWXMFYPEVFEPERGIJYRGXMSR7XYH]SJXLIWIQYXEXMSRWQE]LIPTYRHIVWXERHEGSQQSR LYQERFEPERGIHMWSVHIVFIRMKRTSWMXMSREPZIVXMKS8SKIXLIV[MXLGSPPEFSVEXSVW [ILEZIEPWSYWIHWSPYXMSRL]FVMHMWEXMSR[LSPII\SQIIRVMGLQIRXXIGLRSPSK]XS MWSPEXIERHWIUYIRGIXLITVSXIMRGSHMRKWTEGISJX. tropicalisKIRSQIWHIVMZIHJVSQ GLIQMGEPP]QYXEKIRMWIHWXSGOW8LMWWXVEXIK]LEWVETMHP]]MIPHIHQSVIXLERRI[ QYXEXMSRWJSVJYVXLIVWXYH]ERHMRGPYHIWKIRIWXLEXEVIMQTSVXERXJSVEZEVMIX]SJ TVSGIWWIWMRGPYHMRKGMPMSKIRIWMWPIJXVMKLXEW]QQIXV]ERHIV]XLVSTSMIWMW Publications %FY(E]E%/LSOLE1/ERH>MQQIVQER0& The Hitchhiker’s guide to Xenopus genetics. genesis 50 1EGLE.8IMGLQERSZE67EXIV%;IPPW(8PETEOSZE8 >MQQIVQER0ERH/V]PSZ: Deep ancestry of mammalian X chromosome revealed by comparison with the basal tetrapod Xenopus tropicalis. BMC Genomics 13:315 %FY(E]E%2MWLMQSXS7*EMVGPSYKL01SLYR8.0SKER 143ERH>MQQIVQER0& The secreted integrin ligand nephronectin is necessary for forelimb formation in Xenopus tropicalis. Developmental Biology 349 Xenopus ciliated epidermis mutations model disorders of mammalian lung. grinch (gri) mutant epidermal cilia are fewer and shorter than wild type (wt); stained with an antibody to acetylated tubulin (top), SEM (bottom). 7IIVIJIVIRGIWERHMRXLIFMFPMSKVETL]EXXLI FEGOJSVTYFPMGEXMSRWJVSQXLMWKVSYTMR MRC National Institute for Medical Research 99 ,MWXSPSKMGEPWIGXMSRSJPYRK8&KVERYPSQEJVSQQSYWIXMWWYI[MXLPEVKI½IPHERHGIPPYPEVVIWSPYXMSR8LIWM^ISJXMWWYIMWETTVS\MQEXIP] 10mm X 14mm. The sample was kindly provided by Jonathan Pitt (Division of Immunoregulation). The image was taken on VS120 virtual slide scanner with 20x objective by Kate Sullivan, (Confocal imaging and analysis laboratory). 100 MRC National Institute for Medical Research Research facilities Biological and Procedural Services Structural biology facilities MRC Biomedical NMR Centre X-ray crystallography Mass spectrometry Protein sequence analysis and structure modelling Analytical ultracentrifugation Imaging Confocal imaging and analysis Histology Electron microscopy OPT and HREM imaging Single molecule techniques Electron cryomicroscopy 3XLIVWGMIRXM½GJEGMPMXMIW Bioresources Large scale laboratory Media production Freezer archive Genomics High-throughput sequencing Microarray Flow cytometry Level 4 high-containment virus laboratory Insectary Electronic instrument prototyping and support Mechanical Engineering Other support services Facilities and Infrastructure Services PhotoGraphics Computing and telecommunications Library, information and communications Web Team General services Occupational Health Safety and Security Human Resources Finance and Purchasing MRC National Institute for Medical Research 101 RESEARCH FACILITIES Biological and Procedural Services Kathleen Mathers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½WLERH XenopusWTIGMIW8LIWM^IWGSTIERHIJ½GMIRG] SJ&MSPSKMGEP7IVZMGIWTVSZMHIERI\XVESVHMREV]WIVZMGIXSRIEVP]EPPEWTIGXWSJXLI -RWXMXYXI´WWGMIRGIEW[IPPEWXSQER]WGMIRXMWXWIPWI[LIVI The Institute houses over 800 distinct lines of genetically altered mice. Bioluminescence imaging Individually ventilated cages 102 MRC National Institute for Medical Research RESEARCH FACILITIES ;IEMQXSQIIXEPPXLIRIIHWSJXLIWGMIRXM½G(MZMWMSRW[LMPWXIRWYVMRKXLILMKLIWXTSWWMFPIWXERHEVHWSJLIEPXLERH[IPJEVI JSVEPPWTIGMIW8LI(MZMWMSRMWEGXMZIMRXLI½IPHSJPEFSVEXSV]ERMQEPWGMIRGIGSRHYGXMRKERHTVSQSXMRKVIWIEVGLERHYTXEOISJ XLI6WVITPEGIQIRXVIHYGXMSRVI½RIQIRXERHTVIWIRXWMXW[SVOEXREXMSREPERHMRXIVREXMSREPQIIXMRKW8LIERMQEPGEVIERH XIGLRMGEPWXEJJEVIXVEMRIHMRXLITVSHYGXMSRGEVIERHYWISJERMQEPWJSVVIWIEVGLTYVTSWIWXSXLILMKLIWXWXERHEVHWSJERMQEP LYWFERHV]WIITEKI%HHMXMSREPP]XLI]TVSZMHIEVERKISJGIRXVEPMWIHTVSGIHYVEPWYTTSVX%JYPPXMQIZIXIVMREV]WYVKISRERH QMGVSFMSPSKMWXSJJIVEHZMGISRXLILIEPXLERH[IPJEVISJSYVERMQEPW8LI(MZMWMSREPWSTVSZMHIWWIVZMGIWJSVXLIMRGYFEXMSRSJ JIVXMPIGLMGOIRIKKWERHXLITVSHYGXMSRSJERXMFSHMIW-REHHMXMSREHQMRMWXVEXMSRERHPMGIRGIGSRXVSPYRHIVXLI%RMQEPW7GMIRXM½G 4VSGIHYVIW%GXERHGSSVHMREXMSRSJXLI-RWXMXYXI´W0SGEP)XLMGEP6IZMI[4VSGIWWMWQEREKIHF]&MSPSKMGEP7IVZMGIW Procedural Service Section 8LI4VSGIHYVEP7IVZMGI7IGXMSRTVSZMHIWEVERKISJWIVZMGIWERHJEGMPMXMIWJSVXLITVSHYGXMSR QEMRXIRERGIERHTVIWIVZEXMSRSJKIRIXMGEPP]EPXIVIHVSHIRXW8LIWIVZMGITVSHYGIWYTXSRI[ KIRIXMGEPP]EPXIVIHVSHIRXPMRIWIEGL]IEVF]FSXLXVERWKIRMGERHKIRIXEVKIXIHXIGLRSPSKMIW%JYPP VERKISJXIGLRMUYIWMWIQTPS]IHXSTVSZMHIEGSQTVILIRWMZIWIVZMGIJSVXLIGV]STVIWIVZEXMSRSJ VSHIRXKIVQTPEWQERHQSVIVIGIRXP]XLIWIVZMGILEWI\TERHIHXSMRGPYHIGV]STVIWIVZEXMSRSJ JVSKERH½WLWTIVQEXS^SE-REHHMXMSRXLIWIGXMSRMWVIWTSRWMFPIJSVXLIVIHIVMZEXMSRSJRI[PMRIW MQTSVXIHMRXSXLI-RWXMXYXI)ZIV]]IEVXSKIXLIV[MXL&MSPSKMGEP7IVZMGIWXLI7IGXMSRGSSVHMREXIW SZIVWLMTQIRXWSJPMZIERMQEPWERHJVS^IRKIVQTPEWQXSGSPPEFSVEXSVWEPPSZIVXLI[SVPH8LI WXEJJEVIEPWSWOMPPIHMRERYQFIVSJEWWMWXIHVITVSHYGXMZIXIGLRMUYIWMRGPYHMRKin vitroJIVXMPMWEXMSR ERHMRXVEG]XSTPEWQMGWTIVQMRNIGXMSR[LMGLEVIYWIJYPJSVQEMRXIRERGISJPMRIW[MXLTSSVFVIIHMRK TIVJSVQERGISVXSTVSZMHIEKIQEXGLIHGSLSVXWJSVI\TIVMQIRXW8LIWIGXMSRMWEPWSGSQQMXXIH XSMRZIWXMKEXMRKERHMQTPIQIRXMRKXLI6WF]VIWIEVGLMRKERHHIZIPSTMRKRI[VI½RIQIRXWWYGLEW RSRWYVKMGEPQIXLSHWSJIQFV]SXVERWJIV ES cell microinjection Procedural Services Manager: Sarah Johnson Analysis of murine sperm motility prior to cryopreservation. MRC National Institute for Medical Research 103 RESEARCH FACILITIES MRC Biomedical NMR Centre Tom Frenkiel 'S[SVOIVW+ISJJ/IPP]%PEMR3VIKMSRM 8LI16'&MSQIHMGEP216'IRXVIMWEQYPXMYWIVJEGMPMX]JSV FMSQSPIGYPEVPMUYMHWXEXIRYGPIEVQEKRIXMGVIWSRERGI216[LMGL [EWWIXYTF]XLI16'MRXSTVSZMHIEHZERGIHERH[IPP WYTTSVXIHJEGMPMXMIWJSVYWIF]WGMIRXMWXWJVSQ2-16ERHSXLIVEGEHIQMG VIWIEVGLIWXEFPMWLQIRXW'YVVIRXP]I\XIVREPKVSYTWQEOIYWISJXLI 'IRXVI´WJEGMPMXMIW216WXYHMIWSJXLIX]TIGEVVMIHSYXEXXLI'IRXVI TVSZMHIE[MHIVERKISJMRJSVQEXMSRVERKMRKJVSQXLIEXSQMGPIZIP IKHIXIVQMRMRKXLIT/ESJMRHMZMHYEPLMWXMHMRIKVSYTWMRTVSXIMRW XLVSYKLXSJYPPHIXIVQMREXMSRSJXLIWXVYGXYVIERHH]REQMGWSJTVSXIMRW MRWSPYXMSR%RMQTSVXERXEVIESJETTPMGEXMSRMWXLIMHIRXM½GEXMSRSJ MRXIVEGXMSRWYVJEGIWFIX[IIRXLIGSQTSRIRXWSJQEGVSQSPIGYPEV GSQTPI\IW 8LI'IRXVI´WJEGMPMXMIWGSRWMWXSJJSYVWTIGXVSQIXIVW[MXL,STIVEXMRK JVIUYIRGMIWWTERRMRKXS1,^GSR½KYVIHJSVWXYHMIWSJ FMSPSKMGEPQEGVSQSPIGYPIWMRWSPYXMSR8LVIISJXLIMRWXVYQIRXWLEZI GV]SKIRMGEPP]GSSPIHTVSFIWERHSRIMWIUYMTTIH[MXLEREYXSQEXMG WEQTPIGLERKIV3ZIVXLIRI\XX[S]IEVWXLI'IRXVI[MPPFIRI½XJVSQ WYFWXERXMEPRI[MRZIWXQIRXERH[MPPFIEHHMRKEWTIGXVSQIXIV[MXLER STIVEXMRKJVIUYIRG]SJ1,^8LMW[MPPFISRP]XLIWIGSRHWYGL MRWXVYQIRXMRXLI9/ NMR studies of the effect of K117 ubiquitination on the structure and enzymatic activity of the josephin domain of ataxin-3. (A.Pastore and S. Faggiano of the Division of Molecular Structure, in collaboration with G. Kelly) The structure and spectrum of free josephin are shown in blue; those of josephin in the ubiquitin complex are in green. Magnet of the 800 MHz spectrometer. 104 MRC National Institute for Medical Research 6ITVIWIRXEXMZITYFPMGEXMSRWEVIPMWXIHSRXLI'IRXVI´W[IFWMXI[[[RQVGIRXVIQVGEGYO RESEARCH FACILITIES X-ray crystallography 4VSXIMR<VE]GV]WXEPPSKVETL]MWEXIGLRMUYIXLEXTVSHYGIWEXLVIIHMQIRWMSREPQSHIPSJXLIWXVYGXYVISJETVSXIMREXEXSQMG VIWSPYXMSR8LI<VE]GV]WXEPPSKVETL]JEGMPMXMIW[MXLMRXLI(MZMWMSRSJ1SPIGYPEV7XVYGXYVIEXXLI-RWXMXYXIEVIWXEXISJXLIEVX ERHMRGPYHIELMKLMRXIRWMX]<VE]WSYVGIGSYTPIH[MXLEREYXSQEXIHVSFSXMGWEQTPIQSYRXMRKW]WXIQ[LMGLEPPS[WXLI YREXXIRHIHWGVIIRMRKSJGV]WXEPWMREWMRKPII\TIVMQIRX(MJJVEGXMRKTVSXIMRGV]WXEPWEVIXLIGYPQMREXMSRSJERI\XIRWMZIWIVMIW SJI\TIVMQIRXEPTVSGIHYVIW[LMGLMRGPYHITVSXIMRTYVM½GEXMSRERHTVSXIMRGV]WXEPPMWEXMSR%VERKISJWSTLMWXMGEXIHXIGLRMUYIWMW IQTPS]IHXSLIPTI\TPSVIXLIPEVKIWXRYQFIVSJGSRHMXMSRW[MXLMRIEGLSJXLITVSNIGXWYRHIVMRZIWXMKEXMSR8LIWIMRGPYHIXLSWI XIGLRMUYIWFIMRKHIZIPSTIHMRXLI4VSXIMR)\TVIWWMSR0EFXSKIXLIV[MXLE[MHIVERKISJVSFSXMGTVSGIHYVIWXSWIXYTQYPXM[IPP HMWLIWERHXSEYXSQEXMGEPP]WGVIIRJSVTVSXIMRGV]WXEPW X-ray generator and automated sample mounting robot insert shows the loop used to hold the protein crystal. The Protein Expression Lab[EWIWXEFPMWLIHMR to provide dedicated support to members of the Division of 1SPIGYPEV7XVYGXYVI8LIJEGMPMX]TVSZMHIWEGSQTVILIRWMZI VIWSYVGIJSVXLITVSHYGXMSRSJVIGSQFMRERXTVSXIMRW 'YVVIRXP][ISJJIVEGLSMGISJX[SI\TVIWWMSRW]WXIQW FEGXIVMEERHMRWIGXGIPPW%LMKLXLVSYKLTYXTMTIPMRIJSVGPSRMRK (2%JVEKQIRXWERHWQEPPWGEPII\TVIWWMSRXIWXWMRE. coli has FIIRIWXEFPMWLIHEPPS[MRKXLIKIRIVEXMSRERHWGVIIRMRKSJ I\TVIWWMSRGSRWXVYGXWMRE[IIO-RTEVEPPIPTVSXIMRWEVI EPWSI\TVIWWIHMRMRWIGXGIPPWYWMRKXLIFEGYPSZMVYWI\TVIWWMSR ZIGXSVW]WXIQ&):77IVZMGIWMRGPYHIXLIKIRIVEXMSRERH EQTPM½GEXMSRSJLMKLXMXVIFEGYPSZMVYWWXSGOWEREP]XMGEPWGEPI TVSHYGXMSRWJSVSTXMQMWEXMSRSJTVSXIMRI\TVIWWMSRERH TVITEVEXMZIWGEPITVSHYGXMSRW-REHHMXMSRXLIJEGMPMX]QEMRXEMRW EZIGXSV(2%VITSWMXSV]TVSZMHIWMRLSYWIZIGXSVHIWMKR XVSYFPIWLSSXMRKERHXVEMRMRK To the right is a cartoon representation of the crystal structure of mammalian AMP kinase (AMPK) with 2 bound AMP molecules. To the left is a surface representation of the same molecule. The regulatory subunits are shown in red (gamma-subunit), green (beta-subunit) and cyan (alphasubunit). Two bound molecules of AMP are shown in stick representation. The kinase domain is shown in yellow. Insect cell expression in a Wave Bioreactor™. MRC National Institute for Medical Research 105 RESEARCH FACILITIES Mass spectrometry Steve Howell 8LITVSXISQMGWERHQEWWWTIGXVSQIXV]JEGMPMX]MWLSYWIH MRETYVTSWIFYMPXWYMXI-XGYVVIRXP]LSYWIWXLVIIQEWW WTIGXVSQIXIVWERHERGMPPEV]IUYMTQIRX[LMGLEVIYWIHMRE VERKISJFMSGLIQMGEPEREP]WIW%WXEXISJXLIEVX085:IPSW 3VFMXVETLMKLVIWSPYXMSRXERHIQ17GSYTPIHXSERERS,40' MWYXMPMWIHMRTVSXISQMGWWXYHMIWERHMWGETEFPISJMHIRXMJ]MRK LYRHVIHWSJTVSXIMRWJVSQEWMRKPIVYR4VSXIMRUYERXM½GEXMSR MWTIVJSVQIHYWMRKWXERHEVHXIGLRMUYIWWYGLEW7-0%'SV M86%5PEFIPPMRK-HIRXM½GEXMSRSJXLIWMXIWSJTSWXXVERWPEXMSREP QSHM½GEXMSRWWYGLEWTLSWTLSV]PEXMSRERHYFMUYMXMREXMSRMWEPWS EGLMIZIHSRXLMWMRWXVYQIRX %UYEHVYTSPIXMQISJ¾MKLXXERHIQQEWWWTIGXVSQIXIV IUYMTTIH[MXLERIPIGXVSWTVE]WSYVGIMWYXMPMWIHJSVTVSXIMRERH TITXMHIGLEVEGXIVMWEXMSR%+'17LEWVIGIRXP]FIIREHHIHXS XLIJEGMPMX]ERHMWGYVVIRXP]YWIHMRQIXEFSPSQMGWVIWIEVGLWYGL EWXLIUYERXM½GEXMSRSJJEXX]EGMHW Phosphorylation site localisation by LC MS/MS. The nano-electrospray source of the Orbitrap Velos. (YVMRKXLI2-161EWW7TIGXVSQIXV]JEGMPMX][MPPFI MRGVIEWMRKP]MRXIKVEXIH[MXLXLI'69/0SRHSR6IWIEVGL-RWXMXYXI´W 4VSXIMR%REP]WMWERH4VSXISQMGW'SVI8IGLRSPSK]4PEXJSVQ Bram Snijders LRI Core Technology Platform, Protein Analysis and Proteomics 106 MRC National Institute for Medical Research RESEARCH FACILITIES Protein sequence analysis and structure modelling José Saldanha 'SQTYXEXMSREPXSSPWJSVTVIHMGXMSREREP]WMWERHZMWYEPMWEXMSR GERTVSZMHIMRWTMVEXMSREPRI[[E]WXSPSSOEXHEXERSQEXXIV [LMGLTVSXIMRJEQMP]MWXLIQEMRJSGYWSJVIWIEVGL*VSQLMKL PIZIPTVIHMGXMSRWSJTVSXIMRXSTSPSK]F]XIQTPEXIJVIIQIXLSHW WSQIXMQIWGEPPIHab initioXLVSYKLXLVIIHMQIRWMSREPEPPEXSQ QSHIPWSJTVSXIMRWXVYGXYVIXSHIXEMPIHTVSXIMRPMKERHHSGOMRK WXYHMIWXLISVIXMGEPQIXLSHWHIZIPSTIHFSXLEX2-16ERHMRXLI [MHIVEGEHIQMGGSQQYRMX]GERWYKKIWXRI[MRWMKLXWERHRI[ L]TSXLIWIWPIEHMRKXSXLIHIWMKRSJJVYMXJYPI\TIVMQIRXW %WYTTSVXWIVZMGIJSVTVSXIMRWIUYIRGIEREP]WMWERHWXVYGXYVI QSHIPPMRKMWTVSZMHIH-XHVE[WSRWXEXISJXLIEVXEPKSVMXLQW FIMRKHIZIPSTIHF]I\TIVXWMRXLI(MZMWMSRSJ1EXLIQEXMGEP &MSPSK]EW[IPPEWXLIQER]GSQTYXIVTVSKVEQWJVIIP]EZEMPEFPI JVSQXLIWGMIRXM½GGSQQYRMX]8LIVIMWEPWSERMRLSYWI GSQQIVGMEPGSQTYXIVKVETLMGWTEGOEKIJSVHIXEMPIHXLVII HMQIRWMSREPQSHIPPMRK8LIWIVZMGIMWEZEMPEFPIXSEPP2-16 WGMIRXMWXWERHI\XIVREPGSPPEFSVEXSVW Ribbon representation of the three-dimensional molecular model of murine cytochrome P450 1A1. Publications /E]I6+7EPHERLE.;0Y>0ERH,YPQI)' Helix 8 of the M1 muscarinic acetylcholine receptor: scanning mutagenesis delineates a G protein recognition site. Molecular Pharmacology 79 +VERX.7EPHERLE.;ERH+SYPH%4 A DrosophilaQSHIPJSVTVMQEV]GSIR^]QI5HI½GMIRG]ERHHMIXEV]VIWGYIMRXLI developing nervous system. Disease Models & Mechanisms 3 7EPHERLE.; Humanization of Recombinant Antibodies in ‘Recombinant Antibodies for Immunotherapy’ )H 10MXXPI'EQFVMHKI9RMZIVWMX]4VIWW Endogenous ligand FICZ (centre pale blue molecule) docked to molecular model of murine cytochrome P450 1A1. Heme group of enzyme in green on right (collaboration with Stockinger group). MRC National Institute for Medical Research 107 RESEARCH FACILITIES Analytical ultracentrifugation 8LI-RWXMXYXILEWX[SEREP]XMGEPYPXVEGIRXVMJYKIWPSGEXIHMRXLI(MZMWMSR SJ4L]WMGEP&MSGLIQMWXV]8LIWIMRWXVYQIRXWTVSZMHI½VWXTVMRGMTPI L]HVSH]REQMGERHXLIVQSH]REQMGMRJSVQEXMSRGSRGIVRMRKXLIWM^I WLETIERHEWWSGMEXMSRWXEXISJQEGVSQSPIGYPIW*SVFEWMGETTPMGEXMSRW XLIX[SMRWXVYQIRXW<0%ERH<0-EVIIUYMTTIH[MXL9::MW STXMGWXLEXVIGSVHVEHMEPEFWSVFERGIQIEWYVIQIRXWERHQSRMXSV IZSPZMRKWIHMQIRXEXMSRZIPSGMX]SVWXEXMGWIHMQIRXEXMSRIUYMPMFVMYQ GSRGIRXVEXMSRKVEHMIRXW8LI<0-MWEHHMXMSREPP]IUYMTTIH[MXL6E]PIMKL MRXIVJIVIRGISTXMGWXLEXQIEWYVIGSRGIRXVEXMSRTVS½PIWHMVIGXP]JVSQ WSPYXIVIJVEGXMZIMRHI\KVEHMIRXW -RXIVJIVIRGIERHEFWSVFERGIHEXEEVIVIGSVHIHWMQYPXERISYWP]MRXLI<0- ERHMRWMQTPIW]WXIQWYWIHJSVXLIHIXIVQMREXMSRSJWSPYXMSRQSPIGYPEV [IMKLXWSJTVSXIMRWRYGPIMGEGMHWERHTSP]WEGGLEVMHIW%HHMXMSREPP] F]GSQFMRMRKMRXIVJIVIRGIERHEFWSVFERGIHEXEQIEWYVIQIRXWSJ stoichiometries and association constants for interactions between QSPIGYPIWMRGSQTPI\EWWSGMEXMRKW]WXIQWGERFIEPWSFIYRHIVXEOIR Bottom, optical detection system of the XL-I analytical ultracentrifuge consisting of a UV/Vis spectrophotometer and laser interferometer. A fringe displacement pattern produced by a moving concentration boundary measured by the Rayleigh interference optics of the XL-I is shown above. Left, data from a sedimentation velocity experiment performed on the XL-I. On the right, the continuous HMWXVMFYXMSRSJWIHMQIRXEXMSRGSIJ½GMIRXWXLEXFIWX½XWXLIIZSPZMRKGSRGIRXVEXMSRTVS½PI 108 MRC National Institute for Medical Research RESEARCH FACILITIES Confocal imaging and analysis Yan Gu 'S[SVOIVW(SREPH&IPP'LIR5MER/EXI7YPPMZER 8LI'SRJSGEP-QEKMRKERH%REP]WMW0EFSVEXSV]'-%0TVSZMHIW ERMQEKMRKGSVIJEGMPMX]EX2-168LIJEGMPMX]GSZIVWWM\GSRJSGEP QMGVSWGSTIWXLVII[MHI½IPH¾YSVIWGIRGIQMGVSWGSTIWEQYPXMTLSXSR QMGVSWGSTIEWPMHIVVIEHIVE[IPPTPEXIVIEHIVEWTMRRMRKHMWG8-6* QMGVSWGSTIX[SSJ¾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½\IHWEQTPIMQEKMRKERHLEVH[EVIWSJX[EVIHIZIPSTQIRX XSQIIXXLIRIIHWSJ2-16VIWIEVGLIVW ,MKLVIWSPYXMSRWRETWLSXSJEHE]^IFVE½WLYWMRK7IPIGXMZI4PERI-PPYQMREXMSR Microscope developed by CIAL. Publications Snapshot from a live imaging experiment of germ cells in mouse testis. Investigating the effects of aneuploidy on fertility. 4EGEV]),EEW1%;MPHRIV,%^^EVIPPM6&IPP(1%FVSYW(2ERH+YMPPIQSX* Visualization and genetic manipulation of dendrites and spines in the mouse cerebral cortex and hippocampus using in utero electroporation. Journal of Visualized Experiments e4163 7YPPMZER//PSIWW.5MER'&IPP(,E]%0MR=4ERH+Y= ,MKLXLVSYKLTYXZMVYWTPEUYIUYERXMXEXMSRYWMRKE¾EXFIHWGERRIV Journal of Virological Methods 179 ,EHNMIGSRSQSY(6SXOSTJ7%PI\ERHVI'&IPP(1(MGOWSR&.ERH7EPIGOIV- Flybow: genetic multicolor cell labeling for neural circuit analysis in Drosophila melanogaster. Nature Methods 8 MRC National Institute for Medical Research 109 RESEARCH FACILITIES Histology Radma Mahmood 'S[SVOIVW6EHLM%RERH 8LI,MWXSPSK]WIVZMGITVSZMHIWEVERKISJWIGXMSRMRKXIGLRMUYIWJSV ZMWYEPMWEXMSRSJXMWWYIWXVYGXYVIERHKIRII\TVIWWMSRMRERMQEPVIWIEVGL QSHIPW&]QEOMRKTEVEJ½RFPSGOWSJERMQEPXMWWYIW[ITVSHYGIXLMR WIGXMSRWXLEX[LIRWXEMRIHEPPS[JSVEREP]WMWSJXMWWYIWEXEGIPPYPEVPIZIP 8MWWYIWEVIEYXSQEXMGEPP]TVSGIWWIHIQFIHHIHMRXSTEVEJ½RFPSGOWERH WIGXMSRIHQERYEPP]F]JEGMPMX]LMWXSPSKMWXW7PMHIWKIRIVEXIHEVIWXEMRIH JSVGIPPERHRYGPIEVWXVYGXYVISVPIJXYRWXEMRIHJSVXLIVIWIEVGLIV´W S[RYWI2I[P]EGUYMVIHIUYMTQIRXMRGPYHIWXLI0IMGEEYXSQEXIH XMWWYITVSGIWWSV%74ERHEYXSQEXIHWPMHIWXEMRIV%YXSWXEMRIV <0EW[IPPEWX[SRI[VSXEV]QMGVSXSQIWERHGV]SWXEXW8LI%74 TVSGIWWSVYXMPMWIWXIRHMJJIVIRXTVSGIWWMRKTVSKVEQWHIWMKRIHXS STXMQEPP]QEMRXEMRQSVTLSPSK]SJEPPXMWWYIWJVSQQSYWIIQFV]SWERH RISREXIWVEXWJVSKWERH½WLEW[IPPEWLYQERVIWIEVGLWEQTPIW4EVEJ½R XMWWYIFPSGOWEVIWIGXMSRIHQERYEPP]ERHXLIEYXSQEXIHWXEMRIVMWYWIH JSVLIQEXS\]PMRERHISWMR, )WXEMRMRK7TIGMEPWXEMRWWYGLEW1EWWSR´W 8VMGLVSQIJSVGSPPEKIREVITIVJSVQIHQERYEPP] 7LEVIHVIWSYVGIWEZEMPEFPIXSVIWIEVGLIVWMRGPYHIGV]SWXEXWJSV JVS^IRWIGXMSRWERHEQMGVSXSQIJSVTEVEJ½RWIGXMSRW8LIWIVZMGI EPWSTVSZMHIWXVEMRMRKTVSXSGSPWERHEWWMWXERGIJSVMRZIWXMKEXSVWSR EPPEWTIGXWSJLMWXSPSK]MRGPYHMRKXMWWYI½\EXMSRXMWWYITVSGIWWMRKERH MQQYRSLMWXSGLIQMGEPXIGLRMUYIW Nodes with Lac Z staining in blue and counter-stained with nuclear fast red, Lac Z is found predominantly in the centre/core of the tissue. H&E staining of mouse lung TB granuloma day 134 post aerosol M. tuberculosis infection. Cross-section of frozen Drosophila larva showing the cuticle and circular trachea stained with DAPI (blue) and di-tyrosine immuno-staining (green). Cryosection through the head of a 3 days post-fertilisation 8K¾MEI+*4^IFVE½WLIQFV]S+VIIR!+*4FPYI!(%4- red = WGA. 110 MRC National Institute for Medical Research RESEARCH FACILITIES Electron microscopy Liz Hirst 8LI)1JEGMPMX]LEWFSXLE8VERWQMWWMSR)PIGXVSR1MGVSWGSTI 8)1.ISP)<ERHE7GERRMRK)PIGXVSR1MGVSWGSTI 7)1.ISP'*FSXLSJ[LMGLLEZIFIIRYTKVEHIHXS HMKMXEPTLSXSKVETL]+EXER3VMYWERH7IQ%JSVI VIWTIGXMZIP]8LIVIMWEPWSEHIHMGEXIH)1TVSGIWWMRK PEFSVEXSV]7XEJJJVSQER]HITEVXQIRXEX2-16QE]VIUYIWX 8)1SV7)1MRZIWXMKEXMSRWMRWYTTSVXSJXLIMVWGMIRXM½G WXYHMIW+IRIVEPP]WEQTPIWEVITVSZMHIHF]XLIVIUYIWXIV ERHEREP]WIHF]8)1ERHSV7)1[MXLVIJIVIRGIXSXLI UYIWXMSRWSJWTIGM½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ransmission EM: Endogenous Murine Leukaemia Virus is expressed in P]QTLRSHII\XVEGIPPYPEVWTEGIWSJERMQQYRSHI½GMIRXQSYWIWXVEMR (Immunoregulation). Immuno-EM demonstrates that the essential malaria parasite enzyme SERA6 localises to the intraerythrocytic parasitophorous vacuole of Plasmodium falciparum. (Parasitology) Publications 6YIGOIV%7LIE1,EGOIXX*7YEVI^',MVWX)1%1MPYXMRSZMG/;MXLIVW1EVXMRI^'ERH&PEGOQER 1. Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte. Journal of Biological Chemistry 287 'VY^'6MFIW:/YXINSZE)'E]YWS.0E[WSR:2SVVMW(7XIZIRW.(EZI]1&PMKLX/&ERKW* 1]RIXX%,MVWX)'LYRK6&EPEWOEW2&VSH]701EVXM)ERH&VMWGSI. *S\NVIKYPEXIW¾SSVTPEXIGMPMEEVGLMXIGXYVIERHQSHM½IWXLIVIWTSRWISJGIPPWXSWSRMGLIHKILSK signalling. Development 137 4SP]EOSZE3(IEV(7XIVR-1EVXMR7,MVWX)&E[YQME72EWL%(SHWSR+&VSRWXIMR-ERH&E]PI] 41 Proteolysis of prion protein by cathepsin S generates a soluble `-structured intermediate oligomeric form, with potential implications for neurotoxic mechanisms. European Biophysics Journal 38 Scanning EM: Knock Down of a Drosophila chromatin remodelling factor interferes with compound eye development. (Molecular Neurobiology) MRC National Institute for Medical Research 111 RESEARCH FACILITIES OPT and HREM imaging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imaging of the transcription factor Hnf3` (red) in the mouse embryo. 112 MRC National Institute for Medical Research HREM imaging of mouse embryo tissue structure and 3D morphology. RESEARCH RESE EAR ARC CH H FACILITIES FAC ACIIL LIT LIT TIE IES S Single molecule techniques 7MRKPIQSPIGYPII\TIVMQIRXWKMZIMRWMKLXWMRXSLS[FMSPSKMGEPQSPIGYPIW[SVOERHLS[XLI]EVIWXVYGXYVIH7IZIVEPVIWIEVGL KVSYTWEX2-16ETTP]ERHHIZIPSTQIXLSHWXSWXYH]WMRKPIQSPIGYPIW7SQISJXLIWIXIGLRMUYIWTVSZMHILMKLVIWSPYXMSRMQEKIW SJXLIQSPIGYPIWERHSXLIVWKMZIH]REQMGMRJSVQEXMSREFSYXXLIMRXIVEGXMSRWFIX[IIRTVSXIMRW(2%PMTMHQIQFVERIWERHWQEPP PMKERHQSPIGYPIW TIRF (right) and Optical Tweezers (left) are powerful tools that assist studies of motor proteins which are the molecular machines contained in every cell of the body. (Images by Gregory Mashanov and Justin Molloy) ;ILEZIHIZIPSTIHQIXLSHWXSZMWYEPMWIERHQERMTYPEXIWMRKPIQSPIGYPIW[MXLLMKLXMQIVIWSPYXMSRYWMRKX[SPEWIVFEWIH XIGLRMUYIW8SXEP-RXIVREP6I¾IGXMSR*PYSVIWGIRGI8-6*QMGVSWGST]ERHOptical Tweezers388-6*QMGVSWGST]YWIWXLI IZERIWGIRX½IPHEWWSGMEXIH[MXLEXSXEPP]MRXIVREPP]VI¾IGXIHPEWIVFIEQXSI\GMXI¾YSVSTLSVIWEXXLIWYVJEGISJEQMGVSWGSTI GSZIVWPMT7IRWMXMZIGEQIVEW]WXIQWEVIYWIHXSHIXIGXPMKLXIQMXXIHF]XLI¾YSVSTLSVIW8LIWIQIEWYVIQIRXWLEZIEVIWSPYXMSR SJEVSYRH½ZIRERSQIXVIW[MXLMRQMPPMWIGSRHW3TXMGEP8[II^IVWQEOIYWISJVEHMEXMSRTVIWWYVIXSTMGOYTERHQERMTYPEXI MRHMZMHYEPQSPIGYPIW9WMRKJEWXHIXIGXSVWXLITSWMXMSRSJSTXMGEPP]XVETTIHTEVXMGPIWEVIQIEWYVIH[MXLRERSQIXVITVIGMWMSR WSXLEXJSVGIWERHQSZIQIRXWTVSHYGIHF]WMRKPIQSPIGYPIWGERFIQIEWYVIH8LIVIWSPYXMSRMWEVSYRHSRIRERSQIXVIIZIV] QMPPMWIGSRH Atomic Force Microscopy%*1IREFPIWYWXSEREP]WIXLI WXVYGXYVISJFMSPSKMGEPQSPIGYPIWF]WGERRMRKXLIMVWYVJEGI XSTSPSK]YWMRKEQMGVSJEFVMGEXIHQIGLERMGEPTVSFISV±XMT² 8LI%*1YWIHEX2-16.4/2ERS;M^EVHMWMHIEPP]WYMXIH XSWXYH]MRKFMSPSKMGEPQEXIVMEPWMREUYISYWWSPYXMSREXVSSQ XIQTIVEXYVI%WXLI%*1XMTMWWGERRIHSZIVXLIWEQTPIMX VMHIWSZIVQSPIGYPIW½\IHXSXLIWYVJEGI(I¾IGXMSRWSJXLIXMT EVIQIEWYVIHYWMRKEPEWIVFEWIHTSWMXMSRWIRWSVTVSHYGMRKE XLVIIHMQIRWMSREPXSTSPSKMGEPQETSJXLIWYVJEGI8LIXIGLRMUYI MWMHIEPP]WYMXIHXSWXYHMIWSJQEXIVMEPJSV[LMGLLMKLVIWSPYXMSR H]REQMGMRJSVQEXMSRMWVIUYMVIH8LIYPXMQEXIVIWSPYXMSRHITIRHW SRXLIWLEVTRIWWERHWXMJJRIWWSJXLIWMPMGSRXMTXLIQIGLERMGEP TVSTIVXMIWSJXLIWTIGMQIRERHEPWSYTSRXLIQIGLERMGEP WXEFMPMX]SJXLIPEFSVEXSV]ERHQMGVSWGSTIW]WXIQ*SVWSJX FMSPSKMGEPQSPIGYPIWXLIVIWSPYXMSRMWEVSYRH½ZIRERSQIXVIW 9TTIVTERIPWLS[WEWMRKPIEGXMR½PEQIRXERHEWMRKPIQMGVSXYFYPI18F] Iwan Schaap); lower panels show different phases of bacterial Plasmid DNA replication (by Claudia Arbore). MRC National Institute for Medical Research 113 RESEARCH FACILITIES Electron cryomicroscopy ,MKLVIWSPYXMSRGV]SIPIGXVSRQMGVSWGST]GV]S)1IREFPIW XLIWXVYGXYVISJFMSPSKMGEPQSPIGYPIWERHPEVKIVQEXIVMEPWXSFI ZMWYEPMWIHMREJVS^IRL]HVEXIHWXEXI[MXLSYX½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lice of a three-dimensional tomogram showing the edge of a frozen hydrated cell and a computational model for membrane organelles. Image courtesy of Sebastian Wasilewski 114 MRC National Institute for Medical Research RESEARCH FACILITIES RESEARCH RE R ESE SEAR ARC CH HF FACILITIES ACIL AC CIL ILIT ITIE IES Bioresources Joachim Payne 'S[SVOIVW'LEVPSXXI%YWXMR-ER3PMZIV;MSPIXXE7LIPHSR1EKHEPIRE7SOEPWOE&VMER8VMRREQER.EGOMI;MPWSR The Large Scale Laboratory team has SZIV]IEVWSJGSQFMRIHGIPPGYPXYVI I\TIVMIRGIERHSJJIVWEJYPPGSRWYPXEXMSR WIVZMGIJSVEPPGYPXYVIVIUYIWXW8SHE] [IKVS[E[MHIVERKISJQEQQEPMER MRWIGX]IEWXERHFEGXIVMEPGIPPWJSV VIWIEVGL(MZMWMSRWEX2-16EW[IPP EWGSPPEFSVEXMRK[MXLSXLIV16'ERH EGEHIQMGYRMXW0EWX]IEV[IKVI[ EVSYRHPMXVIWSJL]FVMHSQEERH MRWIGXGIPPWERHPMXVIWSJ]IEWX ERHFEGXIVMEPGYPXYVIW'IPPWGERFI WYTTPMIHUYMGOJVS^IRSVP]WIHYWMRKE 'SRWXERX7]WXIQWGIPPHMWVYTXIV*SV GSRGIRXVEXMRKWYTIVREXERXW[ILEZIE 7EVXSVMYWGVSWW¾S[½PXVEXMSRW]WXIQERH E5YM\WXERHLSPPS[½FVIYRMX 3YVMRLSYWIMedia Production JEGMPMX] LEWJSVQYPEIJSVSZIVTVSHYGXW ERHPEWX]IEVTVSGIWWIHSVHIVW XSXEPPMRKNYWXSZIVPMXVIWSJ VIWIEVGLVIEKIRXWMRGPYHMRKEUYEVXIVSJ EQMPPMSRXYFIWSJDrosophila food and QMGVSFMSPSKMGEPTSYVIHTPEXIW ;ILEZIVIGIRXP]MRZIWXIHMREYXSQEXIH TPEXITSYVMRKXIGLRSPSK]EPPS[MRKYW XMQIXS[SVOGPSWIP][MXLXLIDrosophila KVSYTWHIZIPSTMRKXLIMVGLIQMGEPP] HI½RIHHMIXW8LIMellanby Freezer Archive MWXLI16'´WTYVTSWIHIWMKRIH JEGMPMX]JSVXLIPSRKXIVQWIGYVIWXSVEKI SJJVS^IRQEXIVMEP%XXLIQSQIRX[I EVIVIWTSRWMFPIJSVSZIVLEPJEQMPPMSR WEQTPIW Wioletta inspects a hybridoma culture. Brian sets up one of our bioreactors. MRC National Institute for Medical Research 115 RESEARCH FACILITIES Genomics Abdul Karim Sesay 'S[SVOIVW0IIRE&LE[6SWYR,EVWLE.ERM2EGLMQE/LEXSSR 8LI+IRSQMGWJEGMPMX]TVSZMHIWRI\XKIRIVEXMSRWIUYIRGMRKERHQMGVSEVVE]WIVZMGIW7IVZMGIWMRGPYHIWEQTPITVITEVEXMSRLMKL XLVSYKLTYXWIUYIRGMRKERHQMGVSEVVE]L]FVMHMWEXMSR7YTTSVXMWEPWSTVSZMHIHJSVHEXEEREP]WMW7MXYEXIH[MXLMRXLI(MZMWMSRSJ 7]WXIQW&MSPSK]XLIJEGMPMX]MWIUYMTTIH[MXLWXEXISJXLIEVXMRWXVYQIRXEXMSRJSVKIRSQMGWIUYIRGMRKKIRSX]TMRKERHKIRI I\TVIWWMSRWXYHMIWMRGPYHMRK-PPYQMRE+%--\ERH,M7IURI\XKIRIVEXMSRWIUYIRGIVWXLI%JJ]QIXVM\+IRI'LMTERHXLI -PPYQMREM7GER7]WXIQW Microarray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eena Bhaw-Rosun, Abdul Karim Sessay, Nachima Khatoon and Harsha Jani. High-throughput sequencing ,MKLXLVSYKLTYXWIUYIRGMRKXIGLRSPSKMIWEVIVIZSPYXMSRMWMRKQSPIGYPEVKIRIXMGWZEWXP]I\TERHMRKSYVEFMPMX]XSWXYH]KIRSQI WXVYGXYVILS[KIRIWEVIVIKYPEXIHERHLS[GIPPERHXMWWYIHMJJIVIRXMEXMSRSGGYVW'SQFMRIH[MXLMRGVIEWMRKP]WSTLMWXMGEXIH FMSMRJSVQEXMGWEREP]WMWXLIWIQIXLSHWSJQEWWMZIP]TEVEPPIPWIUYIRGMRKF]W]RXLIWMWEVIPMOIP]XSMQTEGXSREPPEVIEWSJFEWMG FMSPSKMGEPVIWIEVGL[MXLXLIMVEFMPMX]XSKIRIVEXIFMPPMSRWSJFEWIWSJLMKLUYEPMX](2%WIUYIRGIMREQEXXIVSJHE]W-RSVHIVXS QEMRXEMRMXWTSWMXMSREXXLIJSVIJVSRXSJFEWMGVIWIEVGL2-16LEWIWXEFPMWLIHEGIRXVEPRI\XKIRIVEXMSRWIUYIRGMRKGSVIJEGMPMX] 8LIJEGMPMX]GYVVIRXP]WYTTSVXW(2%62%WIUYIRGMRKYWMRKXLI-PPYQMRE+IRSQI%REP]^IV--\JSVVIEHWYTXSFEWIWJSVFSXL 116 MRC National Institute for Medical Research RESEARCH FACILITIES WMRKPIERHTEMVIHIRHVYRWERHXLI-PPYQMRE,M7IUWIUYIRGIV8LI,M7IUTVSZMHIWSYXTYXSJYTXS+FTIVVYR \FTVIEHPIRKXL8LMWJEGMPMX]TVSZMHIWEGSWXIJ½GMIRXWIVZMGITVSHYGMRKVETMHERHLMKLP]EGGYVEXI(2%ERH62%WIUYIRGI HEXE&]EWWMWXMRKEXEPPWXEKIWJVSQI\TIVMQIRXEPHIWMKRPMFVEV]TVITEVEXMSRXSHEXEEWWIQFP]ERHEREP]WMWXLIWIVZMGIHVEQEXMGEPP] I\XIRHWXLIEFMPMX]SJ2-16WGMIRXMWXWXSQEOIHMWGSZIVMIWMRKIRSQMGWITMKIRSQMGWKIRII\TVIWWMSREREP]WMWERHTVSXIMRRYGPIMG EGMHMRXIVEGXMSRW8LIJEGMPMX]LEWE'SZEVMWW]WXIQJSV(2%WLIEVMRKJSVRI\XKIRIVEXMSRWIUYIRGMRKERHJSVGLVSQEXMRWLIEVMRK ;ISJJIVERI\XIRWMZITPEXJSVQJSVUYEPMX]GSRXVSPERHUYERXM½GEXMSRSJ(2%62%ERHTVSXIMRW8LIJSPPS[MRKIUYMTQIRXMW EZEMPEFPIJSV5'EREP]WMWE2ERSHVSTWTIGXVSTLSXSQIXIVX[S%KMPIRX&MSEREP]WIVX[S0MJI8IGLRSPSK]5YFMXW]WXIQW0MJI 8IGLRSPSK])+IPW]WXIQW'EPMTIV0EFGLMT<8W]WXIQ'EPMTIV0EFGLMT+<JSVLMKLXLVSYKLTYXUYEPMX]GSRXVSPERHUYERXM½GEXMSR SJ(2%ERH62% RNA-sequencing predicts different death rates of selecting thymocytes CD4 and CD8 single positive T-cells develop in the thymus from CD4+CD8+ double-positive precursor cells. The cellular and molecular events of this process are not well characterised. We characterised the kinetics of this process using a novel mouse model allowing for experimentally inducible T-cell HIZIPSTQIRXERHMHIRXM½IHERYQFIVSJHIZIPSTQIRXEPP]MRXIVQIHMEXIWYFTSTYPEXMSRW A) DP2 cells have a high susceptibility to death that behaves the same in each transfer. &(4GIPPWLEZIEPS[VIGSZIV]VEXI½XXMRK[MXLELMKLin vivo death rate. -HIRXM½GEXMSRSJRSZIPHIZIPSTQIRXEPMRXIVQIHMEXITSTYPEXMSRWMR T cell development. (A) Tetracycline inducible T cell development (B) Kinetics of developmental restoration (C) Developmental relationship between double-positive and single-positive cells. MRC National Institute for Medical Research 117 RESEARCH FACILITIES Flow cytometry 'S[SVOIVW&LEZMO4EXIP;E]RI8YVRFYPP 8LI¾S[G]XSQIXV]JEGMPMX]TVSZMHIWEWXEXISJXLIEVXLMKL WTIIHWXIVMPIGIPPWSVXMRKWIVZMGI;IWSVXQYPXMTPIX]TIWSJGIPP TSTYPEXMSRWJSVFSXLin vitro and in vivoWXYHMIWWMRKPIGIPPWSVXMRK ERHGPSRMRK-REHHMXMSRMXSJJIVWQYPXMTEVEQIXIV¾YSVSGLVSQI EREP]WMWSJGIPPQEVOIVWERHQIEWYVIQIRXSJGEPGMYQ¾Y\IW ETSTXSWMWGIPPG]GPIERH*6)8 8LIJEGMPMX]WIVZIWEPEVKIRYQFIVSJ2-16VIWIEVGLIVWJVSQ XLI-RJIGXMSRWERH-QQYRMX]+IRIXMGWERH(IZIPSTQIRXERH 2IYVSWGMIRGIWKVSYTW8VEMRMRKMWEPWSTVSZMHIHJSVVIWIEVGLWXEJJ MRGPYHMRK4L(WXYHIRXWERHTSWXHSGXSVEPVIWIEVGLIVW8LIJEGMPMX] MW[IPPIUYMTTIH[MXLJSYVGIPPWSVXIVWMRGPYHMRKX[SGSPSYV &IGOQER'SYPXIV1S*PS<(4WSVXIVWEGSPSYV&IGXSR (MGOMRWSR*%'7%VME--ERHEGSPSYV&IGXSR(MGOMRWSR-R¾Y\ 8LI-R¾Y\MWWMXYEXIHMRWMHIEGSRXEMRQIRXPIZIP'0FMSWEJIX] GEFMRIXJSVWSVXMRKWEQTPIWGPEWWM½IHEX'0%HHMXMSREPP]XLIVI EVIIMKLX¾S[G]XSQIXVMGEREP]WIVWXLEXMRGPYHIEGSPSYV&IGXSR (MGOMRWSR*%'7'EPMFYVEGSPSYV&IGXSR(MGOMRWSR*%'7:IVWI ERGSPSYV*%'7'ERXSEGSPSYV&IGXSR(MGOMRWSR076--ERH EGSPSYV&IGOQER'SYPXIV']ER%(48LIJEGMPMX]EPWSLSYWIW ER%YXSQEGW'IPPWITEVEXSV 118 MRC National Institute for Medical Research Graham Preece RESEARCH FACILITIES Level 4 high-containment virus laboratory ;MXLMRXLIGSQTPI\SJFYMPHMRKWXLEXQEOIYT2-16MWEWYMXISJPEFSVEXSVMIWJSVLERHPMRKZMVYWIW[MXLLMKLTEXLSKIRMGTSXIRXMEP JSVFMVHWLYQERWSVSXLIVQEQQEPW-XWTVIWIRGIMWRIGIWWMXEXIHF]XLI[SVOSJXLI;,3-R¾YIR^E'IRXVI;-'EX2-16 XLEXMRZSPZIWXLILERHPMRKSJMR¾YIR^EZMVYWIWJVSQEPPSZIVXLI[SVPHWYGLEWXLIRSZIP,2ZMVYWTVMSVXSMXWIQIVKIRGIEWE JYPPFPS[RTERHIQMGZMVYW-REHHMXMSRTSSVP]GLEVEGXIVMWIHZMVYWIWEVIEPWSVIGIMZIH7SQISJXLIWIZMVYWIWRSXEFP]ZMVYWIWJVSQ ^SSRSXMG,2MRJIGXMSRWLEZIGSRWMHIVEFPITEXLSKIRMGTSXIRXMEPMRFSXLFMVHWERHLYQERW;SVO[MXLTSSVP]GLEVEGXIVMWIH ZMVYWIWERHZMVYWIWXLEXQMKLXSVHSLEZITERHIQMGTSXIRXMEPVIUYMVIWELMKLHIKVIISJGSRXEMRQIRXXSTVIZIRXXLIWTVIEHSJ MR¾YIR^EZMVYWIWMRXSFMVHWSVXLIIRZMVSRQIRXEW[IPPEWSTIVEXSVTVSXIGXMSRXSQMRMQMWIXLIVMWOSJLERHPMRKZMVYWIWTSXIRXMEPP] LEVQJYPXSQER 8LIJEGMPMX]MWFYMPXXS,IEPXLERH7EJIX])\IGYXMZIVIUYMVIQIRXWERH()*6%VIKYPEXMSRWYRHIVXLI7TIGM½IH%RMQEPW4EXLSKIR 3VHIV-X[EWYWIHJSVXLIKVS[XLERHGLEVEGXIVMWEXMSRSJWEQTPIWSJXLITERHIQMG,2ZMVYWWIRXJVSQEVSYRHXLI[SVPHEX XLIIEVP]WXEKIWSJMXWKPSFEPWTVIEHERHXSKIRIVEXIVIJIVIRGIJIVVIXERXMWIVEXSXLIIQIVKMRKTERHIQMGZMVYWIWJSVZMVYWERXMKIRMG EREP]WIW-XLEWEPWSFIIRYWIHJSVXLIMWSPEXMSRERHGLEVEGXIVMWEXMSRSJLYQERMWSPEXIWSJ,2EZMERMR¾YIR^EZMVYWJSVI\EQTPI JVSQXLI8YVOMWLSYXFVIEOMRLYQERWMR8LIPEFSVEXSV]GETEGMX]LEWFIIRI\XIRHIHXSLEZIX[SWXERHEVHLMKLGSRXEMRQIRX PEFSVEXSV]EVIEWERHX[SPEFSVEXSVMIWIUYMTTIHXSLERHPIMRJIGXIHWQEPPERMQEPWYRHIVLMKLPIZIPGSRXEMRQIRX;MXLXLIIRLERGIH GETEGMX]MREHHMXMSRXSXLIZMVYWWYVZIMPPERGIERHGLEVEGXIVMWEXMSRWXYHMIWSJXLI;-'WMQYPXERISYWWXYHMIWSJXLIQIGLERMWQWSJ HMWIEWIGEYWEXMSRF]EZMERSVSXLIVMR¾YIR^EZMVYWIWGERFIGEVVMIHSYX *IEXYVIWSJXLIPEFSVEXSV]MRGPYHI %RIKEXMZITVIWWYVIEMVVIKMQI[MXL,)4%½PXIVIHMRTYXERHHSYFPI,)4%½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ycobacterium tuberculosisXLIMRZEWMSRSJFPSSHGIPPWF]XLIQEPEVMETEVEWMXIERHXLIKVS[XLSJ XLIVIXVSZMVYWIWXLEXGEYWI%-(7 MRC National Institute for Medical Research 119 RESEARCH FACILITIES Insectary Irene Tumwine 8LIMRWIGXEV]MWEHIWMKREXIHEVIEJSVXLIVIEVMRKSJMRWIGXWERHMRMXMEXMRKQEPEVMEMRJIGXMSRWMRQSWUYMXSIW-XGSRXEMRWEGSPSR]SJ Anopheles stephensi QSWUYMXSIWGSRWMWXMRKSJETTVS\MQEXIP]EHYPXQSWUYMXSIW8LIJEGMPMX]GSRWMWXWSJ WXEXISJXLIEVXXIQTIVEXYVIERHLYQMHMX]GSRXVSPPIHFVIIHMRKGEFMRIXW MRGYFEXSVWJSVTEVEWMXIHIZIPSTQIRX[MXLMRXLIQSWUYMXS EQMGVSWGST]EVIEJSVQSWUYMXSHMWWIGXMSRWERHEREP]WMW Anopheles stephensiMWERMQTSVXERXZIGXSVJSVI\TIVMQIRXEPQEPEVMEMRFSXLVSHIRXWERHLYQER8LIMRWIGXEV]EPPS[WJSVELMKL RYQFIVSJI\TIVMQIRXEPQSWUYMXSXVERWQMWWMSRWWSXLEXPEFSVEXSV]VIWIEVGLGERQSVIGPSWIP]QMQMGGSRHMXMSRWMRXLI½IPH 6ITPMGEXMRKXLIREXYVEPVSYXISJMRJIGXMSRMRQSYWIQSHIPWQEOIWXLIQSHIPWEWVIPIZERXEWTSWWMFPIJSVQSWUYMXSXVERWQMXXIH LYQERQEPEVME The microscopy area A view of the insectary interior The mosquitoes 120 MRC National Institute for Medical Research RESEARCH FACILITIES Electronic instrument prototyping and support Martyn Stopps ;SVOGSRHYGXIHMRGYXXMRKIHKIWGMIRGISJXIRVIUYMVIWRI[ MRWXVYQIRXEXMSRXLEXMWRSXEZEMPEFPIGSQQIVGMEPP]-RWXVYQIRXW EVIHIWMKRIHERHQERYJEGXYVIHJSVETTPMGEXMSRWMRTL]WMSPSK] ERHWMRKPIQSPIGYPIVIWIEVGL;SVOMRTVSKVIWWMRGPYHIW IRLERGIQIRXERHEYXSQEXMSRSJGSQQIVGMEPMQEKMRKETTEVEXYW ERHHIZIPSTQIRXSJQEKRIXMGX[II^IVWJSV(2%VIWIEVGL 9XMPMWMRKGYVVIRXXIGLRSPSKMIWXLIVIWSYVGIMRGSPPEFSVEXMSR [MXLVIWIEVGLIVWIREFPIWGSQTVILIRWMZIW]WXIQHIZIPSTQIRX JVSQMRMXMEPWTIGM½GEXMSRXLVSYKLTVSSJSJGSRGITXXSXLI½REP ETTPMGEXMSR Automated system development / modelling. Proof of concept device illustrating application of embedded processor XIGLRSPSK]TGMRXIVJEGIERH¾YMHMGHIZMGIW MRC National Institute for Medical Research 121 RESEARCH FACILITIES Mechanical Engineering 'S[SVOIVW(IVIO&VI[IV7XIZI'PEVOI4IXIV'SSOWSR6E],IVVMSXX%HEQ,YVWX6MGLEVH.SRIW 1IGLERMGEP)RKMRIIVMRKTVSZMHIWEHIWMKRGSRWXVYGXMSRERH GSQQMWWMSRMRKJEGMPMX]JSVFIWTSOIMRWXVYQIRXW8LMWGERMRZSPZI RI[HIZIPSTQIRXWSVQSHM½GEXMSRWXSI\MWXMRKIUYMTQIRX *EGMPMXMIWMRGPYHI ( ((IWMKR%YXS'%( ,MKLTVIGMWMSRQERYJEGXYVMRK 1MPPMRKQERYEPERH'2' 8YVRMRKQERYEPERH'2' 7LIIXQIXEPJSVQMRK 4PEWXMGZEGYYQJSVQMRK ;IPHMRK 8LII\TIVMIRGIHWXEJJGERQERYJEGXYVIUYMGOSRISJJTVSXSX]TIW JSPPS[IHF]GSRXMRYIHHIZIPSTQIRXERHQSHM½GEXMSRXSTVSHYGI XLIHIWMVIHMXIQSVETTEVEXYW'PSWIPMEMWSRMWQEMRXEMRIH[MXLXLI WGMIRXM½GWXEJJHYVMRKEPPWXEKIWSJHIWMKRERHQERYJEGXYVI3RWMXI VITEMVERHQEMRXIRERGISJPEFSVEXSV]IUYMTQIRXMWEPWSGEVVMIH SYXMRXLI[SVOWLST 8LIZEVMIHJEGMPMXMIWQIERXLEXEHMZIVWIVERKISJTVSNIGXWGERFI [SVOIHSRMRGPYHMRK 1MGVSWGSTIWXEKIW 1MGVSQERMTYPEXSVW 0EWIVKYEVHMRK 8IQTIVEXYVIGSRXVSPPIHGLEQFIVW 7TIGMEPMWXEHETXSVWERH½XXMRKW 122 MRC National Institute for Medical Research Alan Ling RESEARCH FACILITIES Facilities and Infrastructure Services Dave Ion Facilities and Infrastructure Services is an NIMR EHQMRMWXVEXMSRHMZMWMSRSJ½ZIHITEVXQIRXWTVSZMHMRKE[MHIVERKI SJWYTTSVXWIVZMGIWEGVSWWXLI-RWXMXYXI&YMPHMRK7IVZMGIW(SQIWXMG ERH'IRXVEP7IVZMGIW1IGLERMGEP)RKMRIIVMRK7GMIRXM½G)UYMTQIRX 'EVIERH'IRXVEP7XSVIW3REHEMP]FEWMWQSVIXLERTISTPI EVIIRKEKIHSR*EGMPMXMIWEGXMZMXMIWWYTTSVXMRK2-16EGVSWWXLIWI HITEVXQIRXW1SR*VMTPYWHYX]IRKMRIIVMRKGSZIVJVSQXLI VIWMHIRXQEMRXIRERGIXIEQ 1IGLERMGEP)RKMRIIVMRKMWEPWSTEVXSJXLI*EGMPMXMIWXIEQWIITEKI EWEHMVIGXWIVZMGIXSIRHYWIVWGMIRXMWXW Building Services (EVVIR;EVVMRKXSR-ER8SPPMRW+Y],EPPMJE\0]RHE+VE] &YMPHMRK7IVZMGIWTVSZMHIWEXIGLRMGEPFEWIXSXLI -RWXMXYXIJSVFYMPHMRKTVSNIGXWERHPEFVIJYVFMWLQIRXWEW [IPPEWQEMRXEMRMRKXLIFYMPHMRKERHMXWMRJVEWXVYGXYVI-X MWXLILSQISJ*EGMPMX]1EREKIQIRX[MXLVIWTSRWMFMPMX] JSVIZIV]XLMRKWYTTSVXMRKXLIKIRIVEPVYRRMRKSJ2-16 1EMRXIRERGIERH4VSNIGX;SVOJVEQI[SVOGSRXVEGXW XLEXEVITPEGIH[MXL2SVPERHERH:-2'-*EGMPMXMIW TVSZMHIWIVZMGIWXLEXEVIWTIGM½IHERHQSRMXSVIHF] XLI&YMPHMRK7IVZMGIWXIEQ Through Building Services and its partners, Norland and VINCI, a wide range of TVSNIGXWLEZIFIIRHIWMKRIHWTIGM½IHERH built from the knowledge and skills within the teams. In the current year this has included the Ground Floor South East Wing refurbishment for the Division of Physiology and Metabolism, an Insectary and additional aquatics facilities in the New Polio building. MRC National Institute for Medical Research 123 RESEARCH FACILITIES Facilities and Infrastructure Services (cont.) Domestic and Central Services .YPMI(EZMIW (SQIWXMGERH'IRXVEP7IVZMGIWTVSZMHIWGPIERMRKWIVZMGIW KIRIVEPNERMXSVMEPWIVZMGIWERHVIG]GPMRKEPSRK[MXLGIRXVEP JEGMPMXMIWPMOI+PEWW;EWLYT6IGITXMSRERH1EMP1EREKIH EGGSQQSHEXMSRMWTVSZMHIHMRH[IPPMRKWFSXLSRWMXIERH SJJWMXIJSVWXYHIRXWWGMIRXMWXWERHZMWMXMRK[SVOIVW7IVZMGIW EVITVSZMHIHJVSQXS1SR*VMEW[IPPEWWTIGMEP EVVERKIQIRXWJSVSYXSJLSYVW[SVOSRVIUYIWX 7GMIRXM½G)UYMTQIRX'EVI 1IPZMR3GLW(IRRMW3EXIW 7GMIRXM½G)UYMTQIRX'EVI7)'TVSZMHIWEXVMEKIERHVITEMV WIVZMGIXSEGSQTVILIRWMZIVERKISJWGMIRXM½GIUYMTQIRX The current inventory of equipment in use at NIMR numbers MXIQWERHMRGPYHIWIZIV]XLMRKJVSQ+MPWSR4MTIXXIW FIRGLXSTPEFOMXMRGYFEXSVWXLVSYKLXS9086%GIRXVMJYKIW% X]TMGEP]IEV[MPPWIIQSVIXLERMRHMZMHYEPIUYMTQIRXJEYPX VIWSPYXMSRWIMXLIVVITEMVSVIUYMTQIRXVITPEGIQIRX[LMGLIZIV MWQSWXGSWXIJJIGXMZI7XEXMWXMGEPP]SJEPPIUYMTQIRXMRYWI [MPPVIGIMZIEXXIRXMSRJVSQ7)'HYVMRKXLIGSYVWISJE]IEV Central Stores %PPER.IROMRW 8LI'IRXVEP7XSVIW*EGMPMX]TVSZMHIW2-16[MXLEPPHEMP]TVSHYGX RIIHWZMEIWXEFPMWLIHSVHIVMRKW]WXIQW*VSQXLITSMRXSJ HIPMZIV]SRXLIPSEHMRKFEROXS½REPHMWXVMFYXMSRXSIRHYWIVW [MXLTSVXIVEKIXLI'IRXVEP7XSVIWXIEQQSRMXSVWXSGOPIZIPW VITPIRMWLEWVIUYMVIHERHXEOIHIPMZIV]ERHHMWXVMFYXMSRSJEPP KSSHWVIGIMTXWMRXSXLI-RWXMXYXI%WWSGMEXIHSTIVEXMSRWMRXIVQW SJTVSHYGXQSZIQIRXMRGPYHIVYRRMRKXLIHMWGEVHEYXSGPEZI JEGMPMXMIW02SVHIVERHHMWXVMFYXMSREW[IPPEWEVERKISJWTIGMEPMWX KEWIW 124 MRC National Institute for Medical Research RESEARCH FACILITIES PhotoGraphics Joe Brock 'S[SVOIVW.EQMI&VSGO2IEP'VEQTLSVR,E]PI];SSH;EM,ER=EY 8LI4LSXS+VETLMGWWIVZMGITVSZMHIWETVSJIWWMSREP HIWMKRMPPYWXVEXMSRERHMQEKMRKJEGMPMX]XSZMWYEPMWI XLIMRRSZEXMZIVIWIEVGLGEVVMIHSYXEX2-16 3YVJYPP]XVEMRIHXIEQTVSZMHIWE[MHIVERKISJ WTIGMEPMWXWOMPPWYWMRKWXEXISJXLIEVXIUYMTQIRX WSJX[EVIERHXIGLRMUYIW8LIWIMRGPYHIHMKMXEP QERMTYPEXMSRMPPYWXVEXMSR*PEWLERMQEXMSR½PQ QEOMRKERHIHMXMRK(QSHIPPMRKWGERRMRKERH TLSXSKVETL]EW[IPPEWTVSZMHMRKETVMRXMRKGST]MRK ERHFMRHMRKWIVZMGI 8LMWJEGMPMX]MWSTIRXSEPPVIWIEVGLIVW[MWLMRKXS VIPEXIXLIMVWGMIRGIZMWYEPP]XLVSYKLTYFPMGEXMSR HMKMXEPTVIWIRXEXMSRERHTSWXIVW2SZIPQIXLSHW HIZIPSTIHF]YWJSVTVIWIRXMRKWGMIRGIYWMRK MRXIVEGXMZIERMQEXMSRWTVSZMHIQSVIH]REQMGMR HITXLI\TPEREXMSRWERH[IVIKYPEVP]VIGIMZIVIUYIWXWJSVGSTMIWF]VIWIEVGLIVWERHGSQTERMIW[SVPH[MHI[LSVIGSKRMWIXLMW QIHMEEWETS[IVJYPMRJSVQEXMZIXSSP 8LI4LSXS+VETLMGWXIEQHIWMKRERHTYFPMWL2-16TYFPMGEXMSRWWYGLEWXLMWVITSVXXLIMill Hill EssaysERHSXLIVMRLSYWI TYFPMGEXMSRW;IEPWSTVIWIRXXVEMRMRKGSYVWIWXLVSYKLSYXXLI]IEVJSVVIWIEVGLIVW[LS[MWLXSYWIETTPMGEXMSRWWYGLEW%HSFI 4LSXSWLSTERH1MGVSWSJX4S[IV4SMRXXSTVSJIWWMSREPPIZIP %WXLITVSZMHIVSJ%YHMS:MWYEPWYTTSVXXSXLI-RWXMXYXI4LSXS+VETLMGWQEMRXEMRXLIWIQMREVERHQIIXMRKVSSQJEGMPMXMIWSJJIVMRK ½VWXPMRIWYTTSVXXSEPPWXEJJ[MXLVIKEVHWXSXLIWIX¯YTERHVYRRMRKSJPIGXYVIWWIQMREVWERHIZIRXW;ITVSZMHITVSFPIQWSPZMRK WSPYXMSRWEW[IPPEWKIRIVEPQEMRXIRERGIERHVITEMVWIRWYVMRKWQSSXLERHIJJIGXMZIVYRRMRKSJXLIWIVIWSYVGIWJSVFSXLMRLSYWIERH ZMWMXMRKWTIEOIVW;IEPWSHIZIPSTERHIJJIGXRSZIPETTVSEGLIWJSVHMWWIQMREXMRKVIWIEVGLYWMRKZMWYEPXIGLRSPSKMIWXSOIITTEGI[MXL GYVVIRXERHJYXYVIXVIRHWEWZMWYEPXIGLRSPSKMIWTVSKVIWW Composite image showing 3D modelling, illustration and embedded movies within a single animation describing the role of myosin in merozoite infection of red blood cells. 8]TMGEPMPPYWXVEXMSRTVSHYGIHF]4LSXS+VETLMGWZMWYEPMWMRKWGMIRXM½GERH biological processes. MRC National Institute for Medical Research 125 RESEARCH FACILITIES Computing and Telecommunications Clive Lunny 'S[SVOIVW%SQEV%]EH.SWI%]EPE1EYVS*IVRERHIW(IFVE,EVTIV&IR/IWIP/IZMR1G-RIVRI]+VEIQI1MPPEV,EVWLE7LIXL 2EXLER7QMXL'LERHERM;IPQMPPEKI 8LI'SQTYXMRKHITEVXQIRXMWVIWTSRWMFPIJSVHIPMZIVMRKEFVSEHVERKISJ -8WIVZMGIWEX2-16LIPTMRKWXEJJXSEGLMIZIXLIMV[SVOKSEPWERHTVSZMHMRK XLIWYTTSVXRIIHIHXSQIIX2-16´WIZSPZMRKWGMIRXM½GVIUYMVIQIRXW 7IVZMGIW[ITVSZMHIGERFIFVSEHP]GEXIKSVM^IHEW-8WYTTSVXWIVZMGIW MRJVEWXVYGXYVIJEGMPMXMIWERHW]WXIQWERHWSJX[EVIWIVZMGIW8LIWIMRGPYHIXLI QEREKIQIRXERHWYTTSVXSJSYV0%2[MVIPIWWRIX[SVOERHXIPITLSRI W]WXIQWGSQQYRMGEXMSRWW]WXIQWWIVZIVWLSWXMRKQYPXMTPIWIVZMGIWERHE WYTTSVXWIGXMSRJSV;MRHS[W1EGMRXSWLERH0MRY\HIWOXSTERHPETXST4'W ERHSXLIVQSFMPIHIZMGIW 7IVZMGIW[ITVSZMHIEVIEGIRXVEPMWIHHEXEWXSVEKIW]WXIQ[MXLEGETEGMX] SJ8&VITPMGEXIHSJJWMXIJSVHMWEWXIVVIGSZIV]ERHTVSZMHMRKEYXSQEXMG FEGOYTJSVEPPYWIVWERHWGMIRXM½GJEGMPMXMIWE(VSTFS\PMOI½PIWLEVMRK W]WXIQ:42JSVVIQSXIEGGIWWMRXVERIXEGGIWWEZEMPEFPII\XIVREPP][IF WIVZIVWJSVMRXVERIXERHTYFPMG[IFWMXIW-8WIGYVMX]GSPPEFSVEXMSRWIVZMGIW MRGPYHMRKZMHISGSRJIVIRGMRK[MXLVIQSXITVIWIRXEXMSR434-1%4ERH[IF FEWIHIQEMPGLEXERHGEPIRHEVMRKLSWXMRKSJQYPXMTPIHEXEFEWIWMRGPYHMRK WXYHIRXETTPMGEXMSRWERHERMQEPVIGSVHW 126 MRC National Institute for Medical Research RESEARCH FACILITIES Library, information and communications Frank Norman 'S[SVOIVW4EXXM&MKKW0]RWI])EQIW2MGSPE;IWXSR 8LI0MFVEV]WIVZIWXLIMRJSVQEXMSRRIIHWSJWGMIRXM½GWXEJJERH WXYHIRXWEX2-16-XTVSZMHIWSRPMRIEGGIWWXSSZIVNSYVREPW ERHXSPMXIVEXYVIWIEVGLMRKXSSPWPMOI7GSTYW4YF1IHERH1IXEPMF 8LIVIEVII\XIRWMZITVMRXIHNSYVREPFEGO½PIWERHETVMRXIHFSSO GSPPIGXMSREW[IPPEWIEW]EGGIWWXSEHSGYQIRXHIPMZIV]WIVZMGI 0MFVEV]WXEJJTVSZMHIMRHMZMHYEPMWIHLIPTJSVWGMIRXMWXWMRXLIPEFSV SJ½GI)\TIVXEWWMWXERGI[MXLMRJSVQEXMSRWIEVGLMRKMWEZEMPEFPI MRGPYHMRKLIPT[MXLW]WXIQEXMGPMXIVEXYVIVIZMI[WHMJ½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´WQENSVVIWIEVGLSYXTYXWERHEGLMIZIQIRXWIRWYVMRK XLEXXLIWIEVIPMWXIHSRXLI-RWXMXYXI[IFWMXIERHMRXLI%RRYEP 6ITSVX-XEPWSQEMRXEMRW2-16´WLMWXSVMGEPEVGLMZIWERHVITSWMXSV] SJTYFPMGEXMSRW The Library and breakout space. One of the breakout tables. MRC National Institute for Medical Research 127 RESEARCH FACILITIES Web Team Christina McGuire 'S[SVOIV3PM'LS[HLYV] 8LI;IF8IEQMWVIWTSRWMFPIJSVXLIHE]XSHE] QEREKIQIRXSJXLI2-16[IFWMXIMRXVERIXERHSRPMRI TVIWIRGIERHPSRKIVXIVQWXVEXIKMGTVSNIGXWWYGLEW XLIVIGIRXVIHIZIPSTQIRXERHMQTPIQIRXEXMSRSJE GSRXIRXQEREKIQIRXW]WXIQSRXLII\XIVREP[IFWMXI 3YVEMQWEVIXSIRWYVIXLEXXLII\XIVREP[IFWMXI VI¾IGXWXLII\GIPPIRGISJWGMIRGIEX2-16QIIXWYWIV ERHSVKERMWEXMSREPRIIHWERHTVSQSXIWXLIVIWIEVGL ERHSYXVIEGL[SVOEX2-16-RXIVREPP][IEMQXS provide easy access to information and resources XLVSYKLSRPMRIW]WXIQW[LMGLWYTTSVXIJJIGXMZIERH IJ½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nline weekly newsletter for staff 128 MRC National Institute for Medical Research Customisable intranet homepage RESEARCH FACILITIES General services Safety and Security 8LI7EJIX]WIGXMSRTVSZMHIWEWEJI[SVOMRKIRZMVSRQIRX EXXLI-RWXMXYXI%PPWXEJJEVITVSZMHIH[MXLKIRIVEPWEJIX] XVEMRMRKERHEHZMGI7TIGMEPMWXWEJIX]ERHWIGYVMX]XVEMRMRKERH EHZMGIMWEZEMPEFPIJVSQXLVIIWEJIX]SJ½GIVWXLMWMRGPYHIW FMSPSKMGEPVEHMSPSKMGEPGLIQMGEPERH½VIWEJIX]8LIVIMWEPWS WTIGMEPMWXIUYMTQIRXEZEMPEFPIJSVYWI8LIVIMWLSYV WIGYVMX]GSZIVEKI8LIHITEVXQIRXEPWSVIWTSRHWXSEPPWMXI IQIVKIRGMIW Occupational Health 3GGYTEXMSREP,IEPXL3,MWGSRGIVRIH[MXLXLIIJJIGXWSJ LIEPXLSR[SVOERHSJ[SVOSRLIEPXL[MXLGSRWMHIVEXMSRJSV XLI[SVOMRKIRZMVSRQIRX3GGYTEXMSREPWIVZMGIWMRGPYHILIEPXL TVSXIGXMSRLIEPXLTVSQSXMSRERHPSWXXMQIQEREKIQIRX3YV TVSJIWWMSREPWIVZMGISFWIVZIW,IEPXLERH7EJIX]VIKYPEXMSRW ERHLIPTWXSWYTTSVXXLISZIVEPPRIIHWSJ2-16;ISJJIV MQTEVXMEPEHZMGIXSEPPIQTPS]IIWSRLIEPXLQEXXIVWVIPEXIHXS XLI[SVOMRKIRZMVSRQIRX8LI3,XIEQEPWSTVSZMHIWTIGM½G LIEPXLWYVZIMPPERGIXSWXEJJQIQFIVWI\TSWIHXSLE^EVHW Human Resources 8LI,YQER6IWSYVGIWWIGXMSR[SVOWMRTEVXRIVWLMTEGVSWW XLI-RWXMXYXIXSWYTTSVXMXWSFNIGXMZIWERHEHMZIVWIKVSYT SJWGMIRXM½GERHWYTTSVXWXEJJ%XIEQSJWTIGMEPMWXW[SVOXS IQFIHWLEVIHTVMRGMTPIWERHEGYPXYVIXLEXWYTTSVXWGMIRGI ERHTVSZMHII\TIVXEHZMGISRIQTPS]QIRXQEXXIVWWYGL EWVIGVYMXQIRXHIZIPSTQIRXTIVJSVQERGIVI[EVHERH VIGSKRMXMSR Finance and Purchasing The Finance team provides advice and support to staff MRXLIGSWXMRKSJKVERXETTPMGEXMSRWJYPPIGSRSQMGGSWXMRK I\TIRWIWERHWEPIWMRZSMGIW8LI]EVIEPWSVIWTSRWMFPIJSV XLIQEREKIQIRXVITSVXMRKERHJSVIGEWXMRKSJXLI-RWXMXYXI´W FYHKIXW8LI4YVGLEWMRKXIEQEWWMWXWWXEJJ[MXLEPPEWTIGXWSJ TVSGYVIQIRXMRGPYHMRKXIRHIVMRKJSVGETMXEPIUYMTQIRXWIVZMGI GSRXVEGXWERHGSRWYQEFPIW8LI]EPWSPMEMWIGPSWIP][MXLXLI 6'9/7LEVIH7IVZMGI'IRXVIXSIRWYVIXLEX[IKIXFIWXZEPYI JSVQSRI]MRTVMGMRK MRC National Institute for Medical Research 129 Institute management Organisational Structure Director’s Office Director: Dr Jim Smith Director of Research Dr Steve Gamblin Genetics and Development Dr David Wilkinson Developmental Biology Dr Jean-Paul Vincent and Dr James Briscoe Stem Cell Biology and Developmental Genetics Dr Robin Lovell-Badge Systems Biology Dr Jim Smith Neurosciences Dr Vassilis Pachnis Developmental Neurobiology Dr David Wilkinson Molecular Neurobiology Dr François Guillemot Neurophysiology Dr Troy Margrie Physiology and Metabolism Dr Alex Gould Infections and Immunity Drs Jonathan Stoye and Victor Tybulewicz (joint heads) Structural Biology Dr Justin Molloy Immune Cell Biology Dr Victor Tybulewicz Immunoregulation Dr Anne O'Garra Molecular Immunology Dr Gitta Stockinger Mycobacterial Research Dr Douglas Young Parasitology Dr Tony Holder Virology Dr Jonathan Stoye World Influenza Centre Dr John McCauley Mathematical Biology Dr Willie Taylor Molecular Structure Dr Steve Gamblin and Dr Steve Smerdon Physical Biochemistry Dr Justin Molloy NMR Centre Dr Tom Frenkiel Biological Services Procedural Services Student Office Director of Studies: Donna Brown Library and Information Services Assistant Director Mr John Wills Safety and Security PhotoGraphics Web Team Computing and Telecommunications Technology Transfer Bioresources Engineering Services ----Mechanical Engineering ----Electronics Engineering ----Engineering Repair Facilities ----Building Services ----Domestic and Central Services ----Glasswashing ----Stores/Portering Director of Operations Michele Marron Finance ----Accounts ----Procurement ----Purchasing Human Resources ----Occupational Health Last updated 19 September 2012 130 MRC National Institute for Medical Research 'IPPG]GPIVITSVXIVMRXLIHIZIPSTMRK[MRKSJEJVYMX¾]%WGIPPWHMZMHIXLI]JSPPS[EWXIVISX]TIHTVSKVIWWMSRJVSQSRITLEWISJ replication to another. The red, amber and green cells here show cells in different phases of this process. Photo Courtesy of Luis Alberto Baena Lopez MRC National Institute for Medical Research 131 Nobel Laureates *MZIWGMIRXMWXWJVSQ2-16LEZIFIIRE[EVHIH2SFIP4VM^IWJSVXLIMVWGMIRXM½GVIWIEVGL Henry Dale, OM, FRS (1875-1968) ,IRV](EPI[SVOIHEX2-16JVSQMXWMRGITXMSRMRERH[EWXLI½VWX(MVIGXSVWIVZMRKJVSQ ,MWVIWIEVGLSRXLIJYRGXMSRWSJRIVZIGIPPWPIHXSXLIHMWGSZIV]SJEGIX]PGLSPMRIEWE RIYVSXVERWQMXXIVERHXSXLIGLIQMGEPFEWMWSJRIYVSXVERWQMWWMSR*SVXLMW[SVOLIVIGIMZIHXLI2SFIP 4VM^IJSV4L]WMSPSK]SV1IHMGMRIMR Henry Dale Archer Martin, CBE, FRS (1910-2002) %VGLIV1EVXMR[SVOIHEX2-16JVSQ&IJSVIEVVMZMRKEX2-16LI[SVOIHSREQMRSEGMH EREP]WMWERHXLIHIZIPSTQIRXSJTEVXMXMSRGLVSQEXSKVETL]JSVXLITYVM½GEXMSRSJFMSPSKMGEPQSPIGYPIW,I VIGIMZIHXLI2SFIP4VM^IJSV'LIQMWXV]JSVXLMW[SVOMR%X2-16LIHIZIPSTIHXLIQIXLSHSJKEW PMUYMHGLVSQEXSKVETL][LMGLLEWLEHJEVVIEGLMRKMQTEGXSRXLIWXYH]SJFMSGLIQMWXV] Archer Martin Rodney Porter, FRS (1917-1985) 6SHRI]4SVXIV[SVOIHEX2-16JVSQ,MWVIWIEVGLSRXLIQER]WTIGM½GMXMIWSJERXMFSHMIW PIHXSXLIWITEVEXMSRSJERXMKIRFMRHMRK*EFERHGV]WXEPPMRI*GTVSXISP]XMGJVEKQIRXWSJERXMFSHMIW ERIWWIRXMEPWXITJSVXLIHIXIVQMREXMSRSJXLIMVGSQTPIXIWIUYIRGIWSJEQMRSEGMHW*SVXLMW[SVOLI VIGIMZIHXLI2SFIP4VM^IMR4L]WMSPSK]SV1IHMGMRI Rodney Porter John Cornforth, FRS (1914-) .SLR'SVRJSVXL[SVOIHEX2-16JVSQ,IGSQTPIXIHXLI½VWXXSXEPW]RXLIWMWSJXLIRSR EVSQEXMGWXIVSMHWERHMRGSPPEFSVEXMSR[MXL+ISVKI4STNEOLIMHIRXM½IHXLIGLIQMGEPWXVYGXYVISJ GLSPIWXIVSP,IVIGIMZIHXLI2SFIP4VM^IJSV'LIQMWXV]MR John Cornforth Peter Medawar, OBE, OM, FRS (1915-1987) 4IXIV1IHE[EV[EW(MVIGXSVSJ2-16JVSQ,I[EWSRISJXLIJSVIQSWXFMSPSKMWXWSJLMW KIRIVEXMSRERHEPWSELYKIP]KMJXIHTSTYPEVMWIVSJWGMIRGI)EVPMIVMRLMWGEVIIVLIWXYHMIHLS[XLI MQQYRIW]WXIQVINIGXWJSVIMKRXMWWYIKVEJXWERHHMWGSZIVIHXLITLIRSQIRSRSJMQQYRIXSPIVERGI*SV XLMW[SVOLI[EWE[EVHIHXLI2SFIP4VM^IJSV4L]WMSPSK]SV1IHMGMRIMR Peter Medawar 132 MRC National Institute for Medical Research Five famous alumni Brigitte Askonas, FRS (1923-2013) &VMKMXXI-XE%WOSREW[SVOIHEX2-16JVSQ7LI[EW,IEHSJXLI(MZMWMSRSJ-QQYRSPSK] JVSQ7LIQEHIWIQMREPGSRXVMFYXMSRWXSSYVYRHIVWXERHMRKSJXLIQSPIGYPEVFEWMWSJP]QTLSG]XI VIWTSRWIWXSTVSXIMRWERHIWTIGMEPP]XSMRJIGXMSYWEKIRXW Brigitte Askonas Philip D’Arcy Hart, CBE (1900-2006) 4LMPMT(´%VG],EVXNSMRIHXLI16'MR[SVOMRKSRHYWXHMWIEWIWMRGSEPQMRIVWXLIRQSZIHXSXLI 16'8YFIVGYPSWMW6IWIEVGL9RMXYRXMPLIVIXMVIHMR-RLIVERXLI½VWXGSRXVSPPIHGPMRMGEPXVMEP XSWLS[XLIIJ½GEG]SJWXVITXSQ]GMREKEMRWXXYFIVGYPSWMW%PEXIVXVMEPPIHXSXLIMRXVSHYGXMSRSJ&'+ ZEGGMREXMSRMRXLI9/%JXIVLIVIXMVIHLIQSZIHXS2-16[MXLER16'VIWIEVGLKVERX[SVOMRKYRXMP Philip D’Arcy Hart Robert Edwards, CBE, FRS (1925-2013) 6SFIVX)H[EVHW[SVOIHEX2-16JVSQ(YVMRKXLMWXMQILMWMRXIVIWXWQSZIHJVSQTYVI WGMIRGIXSFMSQIHMGMRIERHEHIWMVIXSHSWSQIXLMRKEFSYXLYQERMRJIVXMPMX],MWWXYHMIWSRMRHYGIH SZYPEXMSRERHWYTIVSZYPEXMSRMRQMGITVIWEKIHLMWPEXIV[SVOEX'EQFVMHKI[MXL4EXVMGO7XITXSIMR[LMGL XLI]ETTPMIHWYGLETTVSEGLIWXSLYQERWXLYWFVMRKMRKEFSYXXLIVIZSPYXMSRMRin vitroJIVXMPMWEXMSR*SVXLMW PEXIV[SVOLIVIGIMZIHXLI2SFIP4VM^IJSV4L]WMSPSK]SV1IHMGMRIMR Robert Edwards Charles Harington, FRS (1897-1972) 'LEVPIW,EVMRKXSR[EW(MVIGXSVSJ2-16JVSQERHSZIVWE[XLI-RWXMXYXI´WQSZIJVSQ ,EQTWXIEHXS1MPP,MPP,I[EWERSYXWXERHMRKFMSGLIQMWX[LSGSRXVMFYXIHXSSYVYRHIVWXERHMRKSJXLI XL]VSMHKPERHERHSJXLILSVQSRIWMXTVSHYGIWTEVXMGYPEVP]XL]VS\MRI%RSXLIVEGLMIZIQIRX[EWXLI W]RXLIWMWSJKPYXEXLMSRIERHLIYRHIVXSSOTMSRIIVMRK[SVOMRMQQYRSGLIQMWXV]%W(MVIGXSVLIWXVSRKP] IRGSYVEKIHGSSTIVEXMSRFIX[IIRWGMIRXMWXW[SVOMRKMRHMJJIVIRXHITEVXQIRXW Charles Harington James Lovelock, CBE, FRS (1919-) .EQIW0SZIPSGO[SVOIHEX2-16JVSQ,MWQSWXMQTSVXERXMRZIRXMSR [LMPIEXXLI-RWXMXYXI[EWXLIIPIGXVSRGETXYVIHIXIGXSV[LMGL[EWEFPIXSHIXIGXQMRYXIEQSYRXWSJ GLIQMGEPW3VMKMREPP]HIWMKRIHJSVEREP]XMGEPTYVTSWIWMX[EWEPWSEFPIXSHIXIGXMRHYWXVMEPTSPPYXERXWMRXLI EXQSWTLIVIEPIVXMRKXLI[SVPHXSXLIHERKIVWSJYRGLIGOIHTSPPYXMSR%JXIVPIEZMRK2-16LIFIGEQIER MRHITIRHIRXWGMIRXMWXERHHIZIPSTIHXLI+EME,]TSXLIWMW James Lovelock MRC National Institute for Medical Research 133 In memoriam Neil Brown (1929 - 2012) 2IMP&VS[RHMIHSR%TVMP,I[SVOIHMR2-16´W(MZMWMSRSJ4EVEWMXSPSK] JSV]IEVWMRQEPEVMETEVEWMXIFMSPSK]ERHLSWXMQQYRMX] /IRHVMGO2IMP&VS[REXXIRHIH7SYXLKEXI'SYRX]+VEQQEV7GLSSPXLIR[IRX SRXSHS2EXMSREP7IVZMGIMRXLI6S]EP%VQ]:IXIVMREV]'SVTW-RLI GSQTPIXIHERLSRSYVWHIKVIIMR>SSPSK]EX-QTIVMEP'SPPIKIEPVIEH]WTIGMEPMWMRK MRTEVEWMXSPSK]XLIWYFNIGXXLEX[EWXSHI½RIXLI[LSPISJLMWGEVIIVMRWGMIRGI -RLIGSQTPIXIHEX[S]IEV%RMQEP,IEPXL8VYWXVIWIEVGLWXYHIRXWLMTEXXLI 0SRHSR7GLSSPSJ,]KMIRIERH8VSTMGEP1IHMGMRI *VSQ2IMP[SVOIHMRXLI&MSPSKMGEP6IWIEVGL(MZMWMSRSJXLIHVYK GSQTER]1E]ERH&EOIVMRZIWXMKEXMRKXLIGLIQSXLIVET]SJXV]TERSWSQMEWMW ERHWTIGM½GEPP]JSGYWMRKSRXLIHIZIPSTQIRXSJ1IXEQMHMYQJSVYWIMRXLI XVIEXQIRXSJGEXXPIXV]TERSWSQMEWMW(YVMRKXLMWXMQILI[EWWIGSRHIHXS)EWX %JVMGEXSLIPT[MXLXLI½VWXPEVKIWGEPI½IPHXVMEPSJXLMWGSQTSYRH6IPEXIH work on the interactions between host immunity and the chemotherapeutic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lasmodium knowlesi8LIWI[SVOIVWHIQSRWXVEXIHXLIEFMPMX]SJWIVYQERXMFSHMIWJVSQEP. knowlesi immune monkey to WTIGM½GEPP]VIGSKRMWIFMRHXSERHXLIREKKPYXMREXIERHEKKVIKEXIQSROI]IV]XLVSG]XIWMRJIGXIH[MXLQEXYVIWXEKIWWGLM^SRXW SJXLITEVEWMXI2IMPVI½RIH)EXSR´WWGLM^SRXMRJIGXIHGIPPEKKPYXMREXMSR7-'%XIWXERHPSSOIHEXGLVSRMGP. knowlesi infections in QSROI]WVIRHIVIHWIQMMQQYRIMRZEVMSYW[E]W,IHIQSRWXVEXIHEPSRK[MXLSXLIVGSPPIEKYIWXLEXTEVEWMXIWMWSPEXIHHYVMRK XLIGLVSRMGTLEWI[IVIZEV]MRKXLIMVWYVJEGIERXMKIRW%RXMFSHMIWMRHYGIHF]TVIZMSYW7-'%ZEVMERXWHMHRSXVIGSKRMWIIEGL WYGGIWWMZIZEVMERXETTIEVMRKMRXLIFPSSH-QTSVXERXP]2IMPERHGSPPIEKYIW[IVIEFPIXSWLS[XLEXXLIWIERXMKIRWMRHYGIHZEVMERX WTIGM½GRSRTVSXIGXMZIERHTVSXIGXMZIMQQYRIVIWTSRWIW[LMGLEWWSGMEXIH[MXLXLIMRHYGXMSRSJRI[7-'%ZEVMERXWERH TEVEWMXIOMPPMRKVIWTIGXMZIP] 2IMP´W½RHMRKWHMHRSXWMX[IPP[MXLWSQIQIQFIVWSJXLIQEPEVMEVIWIEVGLGSQQYRMX]EX½VWX,MWL]TSXLIWMWWYKKIWXIHXLEX XLIHIZIPSTQIRXSJERIJ½GMIRXQEPEVMEZEGGMRIQMKLX[IPPFIGSQTVSQMWIHF]XLIEFMPMX]SJXLITEVEWMXIXSYRHIVKSERXMKIRMG ZEVMEXMSRERHXLYWIZEHIXLIMRHYGIHMQQYRMX]-RWSQIUYEVXIVWXLMWL]TSXLIWMW[EWMKRSVIHSVHMWQMWWIHSYXSJLERHEWRS WYGLZEVMEFPIERXMKIRWLEHFIIRJSYRHMRXLIQENSVLYQERQEPEVMETEXLSKIRPlasmodium falciparum and it was not considered XLEXERXMKIRMGZEVMEXMSRSGGYVVIHMRXLMWTEVEWMXI,S[IZIV2IMP´W[SVOVINYZIREXIHXLIWIEVGLJSVXLIWIERXMKIRWMRP. falciparum 8LIHMWGSZIV]MRXLIQMHWSJFSXLXLIERXMKIRWERHXLIQYPXMKIRIJEQMP][LMGLIRGSHIWXLIQIREFPIHWXYHMIWTVSZMHMRK MQTSVXERXERW[IVWXSUYIWXMSRWSJZMVYPIRGITEXLSPSK]ERXMKIRMGZEVMEXMSRERHIZEWMSRSJXLILSWXMQQYRIVIWTSRWIMRP. falciparumMRJIGXMSRW2IMP´WZMWMSRERHLMWXIREGMSYWEHLIVIRGIXSLMWZMI[SJXLIMQTSVXERGISJERXMKIRMGZEVMEXMSRMRMQQYRMX]XS QEPEVME[IVIEGORS[PIHKIHF]LMWTIIVWEXE*IWXWGLVMJXLIPHMRLMWLSRSYVF]XLI;IPPGSQI8VYWXMR 2IMPVIXMVIHJVSQ2-16MRFYXWGMIRXM½GTYFPMGEXMSRWFIEVMRKLMWREQI[IVITYFPMWLIHF]LMWGSPPIEKYIWYTYRXMP 134 MRC National Institute for Medical Research In memoriam Mike Gaze (1927 - 2012) 1MOI+E^IHMIHSR7ITXIQFIVEKIH,I[EW,IEHSJ2-16´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“Dr Gaze is distinguished for his work on mechanisms of regeneration in vertebrates. He [EWXLI½VWXXSWXYH]VIKIRIVEXMSRF]RIYVSTL]WMSPSKMGEPQIXLSHWWSQEOMRKXLITVSGIWWEQIREFPIXSUYERXMXEXMZIWXYH]&]GSQFMRMRK XLMWETTVSEGL[MXLXLIGPEWWMGEPQIXLSHWSJI\TIVMQIRXEPIQFV]SPSK]LILEWTVSHYGIHWXVSRKWYTTSVXJSVGIPPWTIGM½GMX]EWXLIKYMHMRK JEGXSVMRVIKIRIVEXMSR² -REHHMXMSRXSSZIVVIWIEVGLTETIVW1MOI+E^ITYFPMWLIHERMR¾YIRXMEPVIWIEVGLQSRSKVETLThe formation of nerve GSRRIGXMSRW%GSRWMHIVEXMSRSJRIYVEPWTIGM½GMX]QSHYPEXMSRERHGSQTEVEFPITLIRSQIRE%VIZMI[EXXLIXMQITVEMWIHXLI FSSOWE]MRK±XLMWMWXLIQSWXWXMQYPEXMRKERHTIVLETWFIWXEGGSYRXEZEMPEFPISRXLMWHMJ½GYPXFYXMQTSVXERXWYFNIGX² .EQ8EXE[LS[EWLIEHSJXLI0EFSVEXSV]SJ(IZIPSTQIRXEP&MSGLIQMWXV]VIQIQFIVW1MOI+E^IERHLMWMQTSVXERXGSRXVMFYXMSR to research at the Institute: “Some of the studies of the Gaze group on retino-tectal connection and function were carried out with the South African clawed frog Xenopus laevis - the Rolls-Royce of animals for developmental biologists. They had set up a small facility in their own laboratory for rearing and maintaining Xenopus larvae. Mike was most generous when I asked him to provide us with some of their surplus tadpoles while we were setting up a controlled facility in our own laboratory. His group also taught us all we needed to know about fertilising Xenopus eggs, rearing tadpoles, maintaining and feeding them as well as adult animals’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±(V+E^I´W[SVOSRXLI HIZIPSTQIRXSJVIXMRSXIGXEPGSRRIGXMSRWLEHFIIRSJEGSRWMWXIRXP]LMKLWXERHEVHERHLEHWLS[RERMRGVIEWMRKWSTLMWXMGEXMSR SZIVXLI]IEVW²ERHETTVSZIHXLIETTPMGEXMSR,MWKVSYTQSZIHEXXLIIRHSJXLEX]IEVFIGSQMRKXLI16'2IYVEP(IZIPSTQIRX ERH6IKIRIVEXMSR+VSYT-XVIQEMRIHEX)HMRFYVKLYRXMP+E^I´WVIXMVIQIRXMR MRC National Institute for Medical Research 135 In memoriam Tony Barrett (1938 - 2012) 8SR]&EVVIXXHMIHSR3GXSFIVEKIH,I[SVOIHMR2-16´W'SQTYXIV 0EFSVEXSV]JSV]IEVWWTIGMEPMWMRKMRXLIQEXLIQEXMGEPEREP]WMWSJFMSPSKMGEP VIWIEVGLTVSFPIQW 8SR][EWFSVRSR3GXSFIV,IEXXIRHIHWGLSSPERHXIGLRMGEPGSPPIKIMR 2SVXLEQTXSRERHPEXIVKEMRIHE1EXLWHIKVIIEX'LIPWIE'SPPIKISJ7GMIRGIERH 8IGLRSPSK],IXLIRQSZIHXS&MVOFIGO'SPPIKIMREWER16'WGLSPEVERH VIKMWXIVIHEWE4L(WXYHIRXMRXLI(ITEVXQIRXSJ'V]WXEPPSKVETL][MXL(V', 'EVPMWPIEWLMWWYTIVZMWSV,MW4L([SVO[EWSRXLIETTPMGEXMSRSJQEXLIQEXMGEP QIXLSHWMRXLI<VE]GV]WXEPPSKVETLMGEREP]WMWSJQSPIGYPEVWXVYGXYVIW8SR][SVOIH [MXL6I\4EPQIVSRXLIGV]WXEPWXVYGXYVISJT]VMHS\EPTLSWTLEXIS\MQIYWMRK XLIRI[P]HIZMWIHLMKLP]QEXLIQEXMGEPP]JSVQYPEXIH(MVIGX4LEWMRK1IXLSHW,I IZIRXYEPP]WYGGIIHIHMRWSPZMRKXLIWXVYGXYVIXLI½VWXF]HMVIGXQIXLSHWMRXLI HITEVXQIRXERHJSVXLMWKEMRIHLMW4L(MR,MW½VWXTETIV&EVVIXX%2ERH 4EPQIV6%%GXE'V]WXEPPSKVB25ETTIEVIHMR ,I[EWETSWXHSGJVSQEX1-8&SWXSR'SPYQFME9RMZIVWMX]ERH1E\ 4PERGO-RWXMXYXIMR,IMHIPFIVK[LIVILI[SVOIH[MXL/IR,SPQIWSRRI[QIXLSHW SJTLEWIHIXIVQMREXMSRJSVPEVKIQSPIGYPEVWXVYGXYVIW,MWTETIVWSRXLIYWISJXLI *EWX*SYVMIV8VERWJSVQ**8[IVIEQSRKWXXLI½VWXXSEPIVXXLIGV]WXEPPSKVETLMG GSQQYRMX]XSXLMWQIXLSH[LMGLGYXWHS[RXLIXMQIJSVGEPGYPEXMSRSJ*SYVMIVQETWF]EWMKRM½GERXJEGXSV-R8SR]FIGEQI LIEHSJXLI4VSKVEQQMRKERH1IXLSHW+VSYTMRXLI)\TIVMQIRXEP'EVXSKVETL]9RMXEXXLI6S]EP'SPPIKISJ%VX[LIVILIYWIH *SYVMIVXVERWJSVQWJSVMQTVSZIHGSRXSYVMRKXIGLRMUYIWMRQETW -RLINSMRIHXLI'SQTYXIV7GMIRGI+VSYTMR2-16´W)RKMRIIVMRK(MZMWMSRQEMRXEMRMRKLMWIQTLEWMWSRYWMRKQEXLIQEXMGEP QIXLSHWXSTVSGIWWMQEKIHEXEXSKMZIFIXXIVVIWSPYXMSRERHFIXXIVFMSPSKMGEPMRJSVQEXMSR,I[SVOIHTEVXMGYPEVP]SRIPIGXVSR QMGVSKVETLWJSVI\EQTPISJFEGXIVMEPGIPP[EPPWXVYGXYVI]IEWXT]VYZEXIGEVFS\]PEWIXIXVEQIVWERHXLIIR^]QIGEVFSRMG ERL]HVEWI0EXIVLIEPWS[SVOIHSRQSHIPPMRKFMSPSKMGEPIZIRXWWYGLEWEQTLMFMERQMHHPIIEVH]REQMGWERHXLIKVS[XLTEXXIVRW SJGLMGO[MRKFYHW 8SR]´W[SVO[EWVIGSKRMWIHMR[LIRLI[EWKMZIRER16'YRPMQMXIHETTSMRXQIRX-RXLI'SQTYXIV7GMIRGI+VSYT QSZIHSYXSJXLI)RKMRIIVMRK(MZMWMSRERHFIGEQIXLIRI['SQTYXIV0EFSVEXSV]YRHIV1SRMGE.SVHER7LIVIGSQQIRHIHLMW [SVOWE]MRK±8SR]´WWXVIRKXLMWLMWEFMPMX]XSGSQQYRMGEXIZIV]IJJIGXMZIP][MXLWGMIRXMWXWERHXSXVERWPEXIXLIMVTVSFPIQWMRXSE JSVQ[LMGLMWWYMXEFPIJSV?GSQTYXIVEREP]WMWA² (YVMRKLMWGEVIIVEX2-16LI[SVOIH[MXLFMSTL]WMGMWXWIPIGXVSRQMGVSWGSTMWXWRIYVSTL]WMSPSKMWXWHIZIPSTQIRXEPFMSPSKMWXW QSPIGYPEVTLEVQEGSPSKMWXWTEVEWMXSPSKMWXWERHQMGVSFMSPSKMWXW8SR]PIJX2-16MRNSMRMRK&VYRIP9RMZIVWMX]EWE0IGXYVIVMR 'SQTYXIV7GMIRGIERH6IWIEVGL*IPPS[MRXLI(ITEVXQIRXSJ1EXLIQEXMGW[LIVILIGSRXMRYIHXS[SVOSRMQEKIIRLERGMRK XIGLRMUYIW,IFIGEQIER,SRSVEV]*IPPS[SJXLI9RMZIVWMX]MRJSPPS[MRKLMWVIXMVIQIRX6I\4EPQIV6IEHIV)QIVMXYW &MVOFIGO'SPPIKI0SRHSRWEMH±8LIXIGLRMUYISJMQEKIIRLERGIQIRX[LMGL8SR][SVOIHSRJSVWSPSRKLEWRS[FIGSQILMKLP] WSTLMWXMGEXIHERHIRNS]WEQYPXMXYHISJIZIV]HE]ETTPMGEXMSRW-XMWWEJIXSWE]XLEX8SR]QEHIWMKRM½GERXGSRXVMFYXMSRWXSXLMW MQTSVXERXEVIESJWGMIRGI² 8SR]&EVVIXXWXEVXIHLMWGEVIIVEWETVSJIWWMSREPNE^^XVYQTIXIV[LSQEHIVIGSVHMRKWJSVXLI&&'ERH[SVOIH[MXLWIZIVEPSJXLI 9/´WPIEHMRKNE^^QYWMGMERWMRGPYHMRK(YHPI]1SSVI3JPEXI8SR]XSSOXSEVVERKMRKGPEWWMGNE^^TMIGIWJSVXLIIPIGXVSRMGOI]FSEVH ERHVIPIEWIHWIZIVEP'(W[LMGLQEOIZIV]KSSHPMWXIRMRK,IEPWSIRNS]IHWLSSXMRKWUYEWLFEHQMRXSRERHKSPJ7EHP]LIFIGEQI MPPERHLEHEQENSVSTIVEXMSRJVSQ[LMGLLIHMHRSXVIGSZIV,IHMIHTIEGIJYPP]SRXLIQSVRMRKSJ7YRHE]XL3GXSFIV 136 MRC National Institute for Medical Research In memoriam Guy Dodson (1937 - 2012) +Y](SHWSR)QIVMXYW4VSJIWWSVSJ'LIQMWXV]EXXLI9RMZIVWMX]SJ=SVOERH JSVQIV,IEHSJ7XVYGXYVEP&MSPSK]EX2-16HMIHSR(IGIQFIVXLEKIH ,I[EWERSYXWXERHMRK<VE]GV]WXEPPSKVETLIV[SVPHVIRS[RIHJSVLMWVIWIEVGL SRXLIXLVIIHMQIRWMSREPWXVYGXYVISJFMSPSKMGEPP]MQTSVXERXTVSXIMRWTEVXMGYPEVP] MRWYPMRERHJSVLMWWXYHMIWSJXLIQIGLERMWQSJEGXMSRSJRYQIVSYWIR^]QIW ,IEPWSIWXEFPMWLIHX[S½VWXGPEWWGIRXVIWJSVXLIWXYH]SJTVSXIMRWXLI=SVO 7XVYGXYVEP&MSPSK]0EFSVEXSV]ERHXLI7XVYGXYVEP&MSPSK]+VSYTEX2-16,I[EW IPIGXIHEWE*IPPS[SJXLI6S]EP7SGMIX]MR +Y][EWFSVRERHIHYGEXIHMR2I[>IEPERH%X%YGOPERH9RMZIVWMX]'SPPIKI LIKVEHYEXIH&7GWGMIRGIGLIQMWXV]QENSVMR17GGLIQMWXV][MXLEXLIWMW MRGV]WXEPPSKVETL]MRERH4L(MRJSVVIWIEVGLTVMRGMTEPP]YWMRK<VE] EREP]WMWGSQFMRIH[MXLEREP]XMGEPGLIQMWXV],I[EWKVIEXP]EXXVEGXIHF]XLI<VE] GV]WXEPPSKVETL]VIWIEVGLSRPEVKIVFMSPSKMGEPQSPIGYPIWMR(SVSXL],SHKOMR´W PEFSVEXSV]MR3\JSVH9RMZIVWMX]ERHMRLIGEQIXS3\JSVHEWETSWX HSGXSVEPVIWIEVGLEWWMWXERX,IWXE]IHSREWEVIWIEVGLJIPPS[YRXMP(SVSXL]´W VIXMVIQIRXMR8LIVIFIX[IIRERHLITPE]IHXLIPIEHMRKVSPIMR HIXIVQMRMRKXLIWXVYGXYVISJXLI½VWXTSP]TITXMHILSVQSRIMRWYPMRERHPEXIVMR EQENSVGV]WXEPPSKVETLMGTETIVLIVIPEXIHXLILSVQSRI´WGLIQMGEPERHFMSPSKMGEP TVSTIVXMIWXSMXWEXSQMGWXVYGXYVI ,MW[SVOSRMRWYPMRGSRXMRYIHJSPPS[MRKLMWQSZIXS=SVOMRIWTIGMEPP][MXLXLIYWISJQYXERXERHGLIQMGEPP]QSHM½IH ZIVWMSRWSJXLILSVQSRIHIWMKRIHJSVEREP]WMWSJXLILSVQSRI´WWXVYGXYVIEWWIQFP]ERHEGXMSR,IEPWSGSPPEFSVEXIHGPSWIP] [MXLPEFSVEXSVMIWMRTLEVQEGIYXMGEPGSQTERMIWJSVXLITVITEVEXMSRSJMRWYPMRWXLEXGSYPHFIYWIHXSMQTVSZIHMEFIXIWXLIVET] 8LIRYQIVSYWIR^]QIWSJFMSPSKMGEPERHTLEVQEGIYXMGEPMRXIVIWXWXYHMIHMR=SVOMRGPYHIHFEGXIVMEPEQ]PEWIWVMFSRYGPIEWIW(2% K]VEWIERHJYRKEPPMTEWIW+Y]´W[SVOSRPMTEWIWI\IQTPM½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½VWXWSPYXMSRSJXLIWXVYGXYVISJXLIGEXEP]XMGHSQEMRSJXLIQEPEVMEPTVSXIEWI 4J79& *VSQLMWGLIQMWXV]FEGOKVSYRHERHLSRIHF]QER]MR¾YIRGIWEX3\JSVH+Y]HIZIPSTIHEHIITVSSXIHFIPMIJMRXLITEVXMGYPEV ZEPYIXSFMSPSK]SJGV]WXEPWXVYGXYVIWXSMRJSVQERHGLEPPIRKIGLIQMGEPQIGLERMWQW8LI3\JSVHIRZMVSRQIRXEPWSVIMRJSVGIH LMWTSPMXMGEPGSQQMXQIRXERHXLVSYKLVIWIEVGLGSPPEFSVEXMSRWERHGSRXEGXWIWXEFPMWLIHXLIVILIVIQEMRIHGPSWIP]PMROIH[MXL ERHWYTTSVXMZISJWGMIRXMWXWMR-RHME'LMREERH'YFE4IVLETWQSWXMQTSVXERXP]LIEGUYMVIHEWX]PISJWGMIRXM½GPIEHIVWLMTERH EWWSGMEXMSR[MXLJIPPS[WGMIRXMWXWXLEXXSKIXLIV[MXLLMWKVIEXGLEVQ[EWI\XVIQIP]EXXVEGXMZIERH[EWGPIEVP]VI¾IGXIHMRXLIIEWI [MXL[LMGLGS[SVOIVWERHGSHMWGYWWERXWJVSQQYPXMTPIHMWGMTPMRIWERHQER]GSYRXVMIWWSYKLXLMWGSQTER] MRC National Institute for Medical Research 137 In memoriam Ita Askonas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¾YIRGIMRXLI½IPHSJMQQYRSPSK]ERHMRXLIHIZIPSTQIRXERHEHZERGIQIRXSJ MRXIVREXMSREPP]EGGPEMQIHMRZIWXMKEXSVW -XE[EWFSVRMR:MIRREXS'^IGLTEVIRXWMR,IVJEQMP]PIJX%YWXVMEMR ERHWIXXPIHMR'EREHEMR)HYGEXIHEX1G+MPP9RMZIVWMX]MR1SRXVIEPWLI QSZIHXSXLI9RMXIH/MRKHSQMRXLIPEXIWXSHSE4L(MRFMSGLIQMWXV]EX XLI9RMZIVWMX]SJ'EQFVMHKI-RWLISFXEMRIHETSWMXMSRMRXLI&MSGLIQMWXV] (MZMWMSREX2-16XSWXYH]LS[QMPOTVSXIMRWEVIQEHI -RXLIQMHW-XEWXEVXIHWXYH]MRKERXMFSH]W]RXLIWMWERHWIGVIXMSRWLS[MRK XLEXEJXIVMQQYRMWEXMSRERXMFSH]WIGVIXMRKGIPPW[IVIRSXSRP]TVIWIRXMR P]QTLSMHXMWWYIFYXEPWSMRFSRIQEVVS[ERHPYRK-R.SLR,YQTLVI]WIXYTXLI½VWX-QQYRSPSK](MZMWMSREX2-16 ERHMRZMXIH-XEXSFISRISJXLIJSYRHMRKQIQFIVW-RWLI[EWKMZIRETIVQERIRXWXEJJTSWMXMSRMRVIGSKRMXMSRSJLIV ±HMWXMRKYMWLIHVITYXEXMSRMRXLMWGSYRXV]ERHEFVSEHJSVLIVVIWIEVGLMRTVSXIMRW]RXLIWMWERHTEVXMGYPEVP]SRERXMFSH]JSVQEXMSR² %JXIVWXYH]MRKXLIEWWIQFP]ERHWIGVIXMSRSJERXMFSHMIWEPWSORS[REWMQQYRSKPSFYPMRW-XE%WOSREWJSGYWIHSRXLIFILEZMSYV SJ&GIPPWXLIGIPPWXLEXTVSHYGIERXMFSHMIW-RTEVXMGYPEVWLIPSSOIHEX[LMGLERXMFSHMIW[IVITVSHYGIHEJXIVHMJJIVIRXERXMKIRW [IVIEHQMRMWXIVIHXSERMQEPW ,IV[SVOMRXLIWSRXLIVSPISJ8P]QTLSG]XIWMRMRJIGXMSRIWTIGMEPP]MRJIGXMSRW[MXLXLIMR¾YIR^EERHVIWTMVEXSV]W]RG]XMEP ZMVYWIWMWWIIREWLIVQENSVGSRXVMFYXMSR,IV[SVOTEZIHXLI[E]XSYRHIVWXERHMRKZMVEPERXMKIRTVIWIRXEXMSRXS8GIPPW-R WLIFIGEQI,IEHSJXLI(MZMWMSRSJ-QQYRSPSK]EX2-16ETSWXWLILIPHYRXMPWLIVIXMVIHMR %RRI3´+EVVE,IEHSJ2-16´W(MZMWMSRSJ-QQYRSVIKYPEXMSRVIQIQFIVW-XEEWERMRWTMVMRKQIRXSV “Ita was passionate about introducing young scientists to immunology and worked hard to support students from many countries, especially in the developing world. Many of the PhD students and postdocs she trained are now eminent scientists. She also trained many physicians in experimental immunology. She continued to actively advise scientists at all levels taking a great interest in young VIWIEVGLIVWKMZMRKXLIQEHZMGISRI\TIVMQIRXEPERHGEVIIVETTVSEGLIW,IVPMJIPSRKHIITMRXIVIWXMRWGMIRXM½GUYIWXMSRWERHXLIJYXYVISJ MQQYRSPSK]VIWIEVGLMRXLI9/MRWTMVIHYWEPP² 138 MRC National Institute for Medical Research 7GMIRXM½GWIQMREVW 2IEVP]WIQMREVWERHPIGXYVIWF]ZMWMXMRKWTIEOIVWEVIKMZIREXXLI-RWXMXYXIIEGL]IEV)EGLQENSVEVIESJWGMIRGILEWMXWS[R WIQMREVWIVMIWERHXLI1MPP,MPP0IGXYVIWIVMIWMWERERRYEPWIVMIWSJEFSYXXIRPIGXYVIWKMZIRF]IQMRIRXWGMIRXMWXWJVSQEVSYRH XLI[SVPH%WIPIGXMSRSJLMKLPMKLXWJVSQXLITEWX]IEVMWWLS[R Dario Alessi 9RMZIVWMX]SJ(YRHII Gordon Brown 9RMZIVWMX]SJ%FIVHIIR Doreen Cantrell 9RMZIVWMX]SJ(YRHII Teresa Carlomagno 7XVYGXYVEP 'SQTYXMSREP&MSPSK])1&0,IMHIPFIVK+IVQER] Philip Cohen 9RMZIVWMX]SJ(YRHII Barry Dickson -RWXMXYXISJ1SPIGYPEV4EXLSPSK]:MIRRE%YWXVME Douglas Epstein (ITEVXQIRXSJ+IRIXMGW9RMZIVWMX]SJ4IRRW]PZERME97% Sarah-Maria Fendt 1EWWEGLYWIXXW-RWXMXYXISJ8IGLRSPSK] Steven Gerondakis 1SREWL9RMZIVWMX]%YWXVEPME Magdalena Götz 0YH[MK1E\MQMPMERW9RMZIVWMXmX1YRMGL+IVQER] Otto Haller 9RMZIVWMX]SJ*VIMFYVK+IVQER] Harald zur Hausen (/*>+IVQER'ERGIV6IWIEVGL'IRXIV,IMHIPFIVK+IVQER] Edith Heard '267-RWXMXYX'YVMI4EVMW*VERGI Mark Howarth (ITEVXQIRXSJ&MSGLIQMWXV]9RMZIVWMX]SJ3\JSVH Richard W Kriwacki (ITEVXQIRXSJ7XVYGXYVEP&MSPSK]7X.YHI'LMPHVIR´W6IWIEVGL,SWTMXEP1IQTLMW8297% Susan Mango ,EVZEVH9RMZIVWMX]97% Sarkis Mazmanian 'EPMJSVRME-RWXMXYXISJ8IGLRSPSK]97% Linda Partridge 1E\4PERGO-RWXMXYXIJSV&MSPSK]SJ%KIMRK-RWXMXYXISJ,IEPXL]%KIMRKERH+))9'0 Janez Plavec 216'IRXVI2EXMSREP-RWXMXYXISJ'LIQMWXV]0NYFPNERE7PSZIRME Fiona Powrie 9RMZIVWMX]SJ3\JSVH Markus Ralser 'EQFVMHKI7]WXIQW&MSPSK]'IRXVI9RMZIVWMX]SJ'EQFVMHKI Gideon Schreiber (ITEVXQIRXSJ&MSPSKMGEP'LIQMWXV];IM^QERR-RWXMXYXISJ7GMIRGI-WVEIP Alain Vincent 'IRXVIHI&MSPSKMIHY(IZIPSTTIQIRX'2679RMZIVWMXI8SYPSYWI*VERGI Gerhard Wagner ,EVZEVH1IHMGEP7GLSSP97% MRC National Institute for Medical Research 139 Staff honours 2012 Editorial boards Siew Lan Ang -RXIVREXMSREP.SYVREPSJ(IZIPSTQIRXEP&MSPSK] Mike Blackman 40374EXLSKIRW)YOEV]SXMG'IPP James Briscoe 4037&MSPSK](IZIPSTQIRX(IZIPSTQIRXEP&MSPSK]2IYVEP(IZIPSTQIRX (IZIPSTQIRXEP(]REQMGW Denis Burdakov 40373RI%QIVMGER.SYVREPSJ4L]WMSPSK]*VSRXMIVWMR1SPIGYPEV2IYVSWGMIRGI Roger Buxton *)171MGVSFMSPSK]0IXXIVW John Doorbar .SYVREPSJ+IRIVEP:MVSPSK] Paul Driscoll .SYVREPSJ7XVYGXYVEPERH*YRGXMSREP+IRSQMGW40373RI Greg Elgar &VMI½RKWMR*YRGXMSREP+IRSQMGW+IRSQI&MSPSK]ERH)ZSPYXMSR Richard Goldstein &1')ZSPYXMSREV]&MSPSK].SYVREPSJ'LIQMGEP&MSPSK]4)(7 François Guillemot &1'(IZIPSTQIRXEP&MSPSK](IZIPSTQIRXEP'IPP+IRIW (IZIPSTQIRX2IYVEP(IZIPSTQIRX Tony Holder )YOEV]SXMG'IPP1SPIGYPEVERH&MSGLIQMGEP4EVEWMXSPSK] George Kassiotis 403732) Jean Langhorne 40374EXLSKIRW-RXIVREXMSREP.SYVREPSJ4EVEWMXSPSK] Steve Ley 'IPP6IWIEVGL&MSGLIQMGEP.SYVREP Malcolm Logan (IZIPSTQIRXEP(]REQMGW(IZIPSTQIRXEP&MSPSK](IZIPSTQIRX Robin Lovell-Badge 3VKERSKIRIWMW7I\YEP(IZIPSTQIRX&MSPSK]SJ7I\(MJJIVIRGIW John McCauley :MVYW6IWIEVGL:EGGMRI6IWIEVGL Elke Ober (IZIPSTQIRXEP&MSPSK] Anne O’Garra .SYVREPSJ)\TIVMQIRXEP1IHMGMRI Annalisa Pastore 403732)4IIV..&'4VMSR7GMIRGI.IX Andres Ramos 3TIR1EKRIXMG6IWSRERGI.SYVREP Katrin Rittinger &MSGLIQMGEP.SYVREP Benedict Seddon *VSRXMIVWMR-QQYRSPSKMGEP1IQSV]-QQYRSPSK] Steve Smerdon 7GMIRGI7MKREPMRK Jim Smith 8VIRHWMR+IRIXMGW3TIR&MSPSK] Gitta Stockinger *VSRXMIVWMR-QQYRSPSK] Jonathan Stoye .SYVREPSJ:MVSPSK] James Turner )HMXSVMEP%HZMWSV]&SEVH'LVSQSWSQI6IWIEVGL&MSPSK]SJ6ITVSHYGXMSR Victor Tybulewicz *VSRXMIVWMR&GIPP&MSPSK]*VSRXMIVWMR8GIPP&MSPSK]*EGYPX]SJ Jean-Paul Vincent 7GMIRGI7MKREPPMRK(IZIPSTQIRXEP&MSPSK] David Wilkinson 1IGLERMWQWSJ(IZIPSTQIRX+IRI)\TVIWWMSR4EXXIVR(IZIPSTQIRXEP&MSPSK]*EGYPX]SJ &MS1IH'IRXVEP(IZIPSTQIRXEP&MSPSK] Robert Wilkinson -RXIVREXMSREP.SYVREPSJ8YFIVGYPSWMWERH0YRK(MWIEWI8YFIVGYPSWMW403732) Mark Wilson 40374EXLSKIRW Douglas Young 8YFIVGYPSWMW Lyle Zimmerman KIRIWMW 8LI.SYVREPSJ+IRIXMGWERH(IZIPSTQIRX 140 MRC National Institute for Medical Research Staff honours 2012 (cont.) 7GMIRXM½G'SQQMXXIIWERH7GMIRXM½G%HZMWXSV]&SEVHW7%& Mike Blackman 1IQFIV7:7)1MGVSFMSPSK]-QQYRSPSK]ERH-RJIGXMSR+VERX)ZEPYEXMSR4ERIP%KIRGI2EXMSREPI HIPE6IGLIVGLI%26*VERGI )\IGYXMZI'SQQMXXIIQIQFIV)9)ZM1EPEV2IX[SVOSJ)\GIPPIRGI 'SSVHMREXSVSJ³-RXIV1EP8VEMRMRK´)91EVMI'YVMI-RMXMEP8VEMRMRK2IX[SVO James Briscoe ;IPPGSQI8VYWX)\TIVX6IZMI[+VSYT 6SWPMR-RWXMXYXI7GMIRXM½G%HZMWSV]&SEVH 'SQTER]SJ&MSPSKMWXW 0´%KIRGI2EXMSREPIHIPE6IGLIVGLI*VERGI Roger Buxton *IPPS[SJXLI7SGMIX]SJ&MSPSK] Luiz Pedro de Carvalho 7GMIRXM½G7XIIVMRK;SVOMRK+VSYT77;+JSV2-,2-%-(WTSRWSVIH'SQQYRMX]%RRSXEXMSR 4VSNIGXSJMycobacterium tuberculosis Genome John Doorbar -RWXMXYX2EXMSREPHY'ERGIV Paul Driscoll 1IQFIV)\XIVREP%HZMWSV]&SEVH,IRV];IPPGSQI2160EFSVEXSVMIW&MVQMRKLEQ9RMZIVWMX] 'LEMVQER)\IGYXMZI'SQQMXXII'SPPEFSVEXMZI'SQTYXMRK4VSNIGXJSV216 Alex Gould ;IPPGSQI8VYWX4IIV6IZMI['SPPIKI Ad hocQIQFIVSJ;IPPGSQI8VYWX-RZIWXMKEXSV%[EVHW7IPIGXMSR4ERIP 9/1IXEFSPMG(MWGYWWMSR+VSYT *VERGMW'VMGO-RWXMXYXI'ERGIV6IWIEVGL7XVEXIK];SVOKVSYT *VERGMW'VMGO-RWXMXYXI7]QTSWME'SSVKERMWIV 6S]EP&VSQTXSR,SWTMXEP6IWIEVGL'SRWSVXME9WIV+VSYT François Guillemot 7IPIGXMSR'SQQMXXIIJSVXLI4IXIVERH4EXVMGME+VYFIV-RXIVREXMSREP6IWIEVGL%[EVH in Neuroscience Tony Holder ;IPPGSQI8VYWX)\TIVX6IZMI[+VSYT4EXLSKIRFMSPSK]ERHHMWIEWIXVERWQMWWMSR Ed Hulme 1IQFIV7GMIRXM½G%HZMWSV]&SEVHSJ,ITXEVIW8LIVETIYXMGW Jean Langhorne ;IPPGSQI8VYWX)\TIVX6IZMI[+VSYT±-QQYRI7]WXIQMR,IEPXLERH(MWIEWI² Steve Ley MRC Infections and Immunity Board Robin Lovell-Badge 7IRWI%FSYX7GMIRGI%HZMWSV]'SYRGMP7GMIRGI1IHME'IRXVI%HZMWSV]&SEVH4VIWMHIRXSJXLI -RWXMXYXISJ%RMQEP8IGLRSPSK]'SSTXIHQIQFIVSJXLI7GMIRXM½GERH'PMRMGEP%HZERGIW %HZMWSV]'SQQMXXIISJXLI,YQER*IVXMPMX]ERH)QFV]S%YXLSVMX],*)%1IQFIVERH 7IGVIXEV]SJXLI.YV]JSVXLI&&:%*SYRHEXMSR*VSRXMIVWSJ/RS[PIHKI&MSQIHMGMRI%[EVH 6S]EP7SGMIX]1IQFIVSJ'SYRGMP4YFPMG0MFVEV]SJ7GMIRGI4037&SEVH1IQFIV1IQFIVSJ *IPHFIVK*SYRHEXMSR%[EVH'SQQMXXII1IQFIVSJ,*)%4YFPMG(MEPSKYI3ZIVWMKLX+VSYTSR 1MXSGLSRHVMEPXVERWJIV Justin Molloy ;IPPGSQI8VYWX)\TIVX6IZMI[+VSYT &&76'8SSPWERH6IWSYVGIW (VIWHIR'&+1E\4PERGO6IZMI[4ERIP Andrew Oates 7XIIVMRK'SQQMXXII)YVSTIER7GMIRGI*SYRHEXMSR6IWIEVGL2IX[SVOMRK4VSKVEQQI John Offer 6S]EP7SGMIX]SJ'LIQMWXV]4VSXIMRERH4ITXMHI7GMIRGIKVSYT Anne O’Garra 7GMIRXM½G%HZMWSV]&SEVH/I]WXSRI'SRJIVIRGIW'SPSVEHS97%16'%&4-9/-R¾EQQEXMSR ERH-QQYRSPSK]-RMXMEXMZI7XIIVMRK+VSYT)6'+VERX%HZERGIH6IWIEVGLIV+VERXW 07(MEKRSWXMGXSSPWXLIVETMIWERHTYFPMGLIEPXL7GMIRXM½G%HZMWSV]&SEVH-RWXMXYXIJSV &MSQIHMGEP7GMIRGIW&IPPMR^SRE7[MX^IVPERH7GMIRXM½G%HZMWSV]&SEVH&E]PSV-RWXMXYXIJSV -QQYRSPSK](EPPEW97% 6S]EP7SGMIX]'SQQMXXII7' Annalisa Pastore 7GMIRXM½G%HZMWSV]&SEVHSJ&MSXIGLRSPSK]-RWXMXYXIMR,IPWMROM*MRPERH 6IJIVIIJSVXLI½VWX7GMIRGI)ZEPYEXMSRSJ-XEPMER-RWXMXYXMSRWSVKERM^IHF]XLI-XEPMER1MRMWXV]SJ Education 'SSVKERM^IVSJ)4*0)8,[SVOWLST1SPIGYPEV'VS[HMRK%WGSRE-WG;SVOWLST(MWGYWWMSR KVSYTSR-VSR7YPJYVGPYWXIVTVSXIMRW0SRHSR Steve Smerdon (MEQSRH0MKLX7SYVGI7GMIRXM½G%HZMWSV]'SQQMXXII MRC National Institute for Medical Research 141 Staff honours 2012 (cont.) Jim Smith 1IQFIV7GMIRXM½G%HZMWSV]&SEVH8[MWX(\%717GMIRXM½G 7YFNIGX,IEHJSV(IZIPSTQIRXEP&MSPSK]&MSPSK]-QEKI0MFVEV] 1IQFIV7GMIRXM½G%HZMWSV]&SEVH-RWXMXYXIJSV8S\MGSPSK]ERH+IRIXMGW/EVPWVYLI 1IQFIV7GMIRXM½G%HZMWSV]'SYRGMP-RHMER-RWXMXYXISJ7GMIRGI)HYGEXMSRERH6IWIEVGL--7)6 1IQFIV7GMIRXM½G%HZMWSV]'SQQMXXII&MSWGMIRGIWERH&MSIRKMRIIVMRK+VSYTEX-RHMER -RWXMXYXISJ8IGLRSPSK]-RHSVI +SZIVRSVERH'LEMVSJ)HYGEXMSR'SQQMXXII0EX]QIV9TTIV7GLSSP 'LEMV6S]EP7SGMIX];IPPGSQI8VYWX7MV,IRV](EPI*IPPS[WLMT-RXIVZMI['SQQMXXII (MVIGXSVSJ6IWIEVGL*VERGMW'VMGO-RWXMXYXI Gitta Stockinger )6'7XEVXMRK+VERXWTERIP %GEHIQ]SJ*MRPERHTERIP )1&3PSRKXIVQJIPPS[WLMTTERIP *'8KVERXTERIP4SVXYKEP %HZMWSV]&SEVH(ITEVXQIRXSJ&MSQIHMGMRI&EWIP %HZMWSV]&SEVH(6*>&IVPMR Victor Tybulewicz 'SYRGMPSJ%GEHIQ]SJ1IHMGEP7GMIRGIW %XMTI%ZIRMVGEVIIVHIZIPSTQIRXJIPPS[WLMTWSJXLI'267ERH-27)61'LEMV Jean-Paul Vincent %GEHIQ]SJ1IHMGEP7GMIRGIW7IGXMSREPGSQQMXXII'LEMV7%&SJXLI-RWXMXYXHI FMSPSKMIHY(IZIPSTTIQIRXHI1EVWIMPPI'LEMV)ZEPYEXMSR'SQQMXXIIISJXLI (ITEVXQIRXSJ(IZIPSTQIRXEP&MSPSK]SJXLI-RWXMXYX'YVMI David Wilkinson )1&30SRK8IVQ*IPPS[WLMTW'SQQMXXII ;IPFMS7GMIRXM½G'SYRGMP 1SYWI%XPEWERH+IRI)\TVIWWMSR(EXEFEWI)1%+) +IRI)\TVIWWMSR(EXEFEWI+<( ,IPQLSPX^7SGMIX]&MSMRXIVJEGIW4VSKVEQ Robert Wilkinson 7GMIRXM½G%HZMWSV]&SEVH1IQFIV8LI%JVMGE'IRXVIJSV,IEPXLERH4STYPEXMSR7XYHMIW 1XYFEXYFE/[E>YPY2EXEP 8VYWXIIERHFSEVHQIQFIV7SYXL%JVMGER'IRXVIJSV)TMHIQMSPSKMGEPEREP]WMWERHQSHIPMRK 7XIPPIRFSWGL9RMZIVWMX]'ETI8S[R7SYXL%JVMGE Douglas Young ;IPPGSQI8VYWX(&8-RHME%PPMERGI7IRMSV*IPPS[WLMT4ERIP 8YFIVGYPSWMW:EGGMRI-RMXMEXMZI8&:-+SZIVRERGI&SEVH %IVEW&MSQEVOIVWERH'SVVIPEXIW;SVOMRK+VSYT -RWXMXYXISJ-RJIGXMSYW(MWIEWIWERH1SPIGYPEV1IHMGMRI--(11'ETI8S[R7GMIRGI%HZMWSV] /[E>YPY2EXEP6IWIEVGL-RWXMXYXIJSV8YFIVGYPSWMWERH,-:/6-8,(YVFER7GMIRGI%HZMWSV] 3VGLMH4VSNIGX+7/(MWIEWIWSJXLI(IZIPSTMRK;SVPH8VIW'ERXSW7GMIRGI%HZMWSV] 16''IRXVIJSV1SPIGYPEV&EGXIVMSPSK] -RJIGXMSR'1&--QTIVMEP'SPPIKI1EREKIQIRX Committee ;,3-R¾YIR^E'IRXVI -RXIVREXMSREP*IHIVEXMSRSJ4LEVQEGIYXMGEP1ERYJEGXYVIVW %WWSGMEXMSRW 142 MRC National Institute for Medical Research PhD theses awarded in 2012 Name Division Title of thesis Daniela Drechsel 1SPIGYPEV2IYVSFMSPSK] Emma Cookson 4L]WMGEP&MSGLIQMWXV] John Ewbank -QQYRSVIKYPEXMSR Victoria Felton :MVSPSK] Thorsten Gantke -QQYRI'IPP&MSPSK] Claire Hastings 4EVEWMXSPSK] Joseph Hedden 1SPIGYPEV7XVYGXYVI Saira Hussain :MVSPSK] +IRSQI[MHIEREP]WMWSJX[SXVERWGVMTXMSREPTVSKVEQQIWSJ RIYVSKIRIWMW 'LEVEGXIVMWEXMSRSJXLI;IMFIP4EPEHIFSH]JYWMSRTSVIYWMRK STXMGEPERHIPIGXVSGLIQMGEPXIGLRMUYIW Mycobacterium tuberculosis induced transcription in QEGVSTLEKIWVSPISJ840)6/WMKREPPMRKMRRIKEXMZI VIKYPEXMSRSJ8]TI--RXIVJIVSRTVSHYGXMSRERHMQTPMGEXMSRW JSVGSRXVSPSJXYFIVGYPSWMW 7XYHMIWSJXLIVIKYPEXMSRSJXLI*ZKIRIMQTPMGEXMSRWJSV VIXVSZMVEPVIWXVMGXMSR 4VSHYGXMSRERHGLEVEGXIVM^EXMSRSJXLI840%&-22* O&TGSQTPI\ 2SZIPQEPEVMETEVEWMXITVSXIMRWMRZSPZIHMRIV]XLVSG]XI invasion 8LIVSPISJ'PTERH4GJMR8VERWGVMTXMSRERHTVIQ62% ´IRH4VSGIWWMRK -QMRSWYKEVWEWERXMZMVEPWEKEMRWXLYQERMR¾YIR^E%ZMVYWIW Steven Moore (IZIPSTQIRXEP2IYVSFMSPSK] 8LIVIKYPEXSV]PSKMGSJ4E\I\TVIWWMSRMRXLIRIYVEPXYFI Rosalind Morley (IZIPSTQIRXEP2IYVSFMSPSK] Aylin Morris-Davies 1SPIGYPEV7XVYGXYVI Lily Nematollahi 1SPIGYPEV7XVYGXYVI Hui Lin Dorothy Ng 4EVEWMXSPSK] Ana Penedos 7XIQ'IPP&MSPSK]ERH (IZIPSTQIRXEP+IRIXMGW -RZIWXMKEXMSRMRXSXLIGIPPYPEVQIGLERMWQYWYRHIVP]MRKGIPP WSVXMRKF])TLVIGITXSVWERHITLVMRW *YRGXMSREPGLEVEGXIVM^EXMSRSJTSP]YFMUYMXMRGLEMRWMRMQQYRI WMKREPPMRK 216ERHFMSTL]WMGEPMRZIWXMKEXMSRSJHIEXLHSQEMR EWWIQFPMIW -QTEGXSJWIUYIRXMEPLIXIVSPSKSYWMRJIGXMSRSRTVIZMSYWP] IWXEFPMWLIHLYQSVEPMQQYRMX] 6IKYPEXMSRSJ,STJYRGXMSRF]1IG8IPTLSWTLSV]PEXMSRW Jonathan Pitt -QQYRSVIKYPEXMSR Ridzuan Razak 4EVEWMXSPSK] Andrea Ruecker 4EVEWMXSPSK] Lasse Stach 1SPIGYPEV7XVYGXYVI Katarina Timofeev 1SPIGYPEV2IYVSFMSPSK] 8LIVSPISJMRXIVPIYOMRMRWYTTVIWWMSRSJMycobacterium tuberculosis infection and BCG vaccination in resistant and WYWGITXMFPIQSYWIWXVEMRW -RZIWXMKEXMRK+%4PSGEPMWEXMSRERHTLSWTLSV]PEXMSRHYVMRK Plasmodium falciparumWGLM^SRXHIZIPSTQIRX ,SQMRKMRSRKIXXMRKSYX'LEVEGXIVMWEXMSRSJ7)6%E TYXEXMZIQEPEVMEPTVSXIEWI[MXLEVSPIMRIKVIWW 7XVYGXYVEPERHJYRGXMSREPEREP]WIWSJTLSWTLSWIVMRI TLSWTLSXLVISRMRIFMRHMRKHSQEMRW 6IKYPEXMSRSJPE]IVWTIGM½GE\SRXEVKIXMRKMRXLIHIZIPSTMRK ZMWYEPW]WXIQSJDrosophila MRC National Institute for Medical Research 143 MRC Centenary award winners -R.YRIXLI16'E[EVHIH2-16EWYFWXERXMEPWYQSJQSRI]XSLIPTWYTTSVXIEVP]GEVIIVVIWIEVGLIVW[MXL16''IRXIREV])EVP] 'EVIIV%[EVHW*SPPS[MRKETERIPVIZMI[XLI(MVIGXSVQEHIE[EVHWPMWXIHFIPS[*VSQIEGLGEXIKSV]XLI³FIWXSJKVSYT´[EW WIPIGXIHWLS[RMRFSPH PLT Awards Dimitrios Anastasiou 4L]WMSPSK]ERH1IXEFSPMWQ John Offer 4L]WMGEP&MSGLIQMWXV] Peter Thorpe7XIQ'IPP&MSPSK]ERH (IZIPSTQIRXEP+IRIXMGW Venizelos PapayannopouloW1SPIGYPEV-QQYRSPSK] Mark Wilson 1SPIGYPEV-QQYRSPSK] Luiz De Carvalho 1]GSFEGXIVMEP6IWIEVGL Fellowships CDFs Aylin Morris-Davies 1SPIGYPEV7XVYGXYVI Benjamin Richier 1SPIGYPEV2IYVSFMSPSK] Lasse Stach 1SPIGYPEV7XVYGXYVI George Young -QQYRSVIKYPEXMSR Robert Moon 4EVEWMXSPSK] Jonathan Pitt -QQYRSVIKYPEXMSR Elizabeth Underwood 1SPIGYPEV7XVYGXYVI Emma Cookson 4L]WMGEP&MSGLIQMWXV] Lily Nematollahi 1SPIGYPEV7XVYGXYVI Student Awards Alex Brown 2IYVSTL]WMSPSK] Sean Constable (IZIPSTQIRXEP2IYVSFMSPSK] Harald Hartweger -QQYRI'IPP&MSPSK] Wilson Li :MVSPSK] Laura Robertson 1SPIGYPEV7XVYGXYVI Anna Strobl 7]WXIQW&MSPSK] Roberta Azzarelli 1SPIGYPEV2IYVSFMSPSK] Kat Collins 1SPIGYPEV7XVYGXYVI Ashleigh Howes -QQYRSVIKYPEXMSR Training & Travel Awards Martin Carkett (IZIPSTQIRXEP&MSPSK] Clare Davy :MVSPSK] Maria Elena Ledesma Fernandez7XIQ'IPP&MSPSK]ERH (IZIPSTQIRXEP+IRIXMGW Olivia Mitchell -QQYRI'IPP&MSPSK] Roksana Ogrodowicz 1SPIGYPEV7XVYGXYVI Victoria Pelly 1SPIGYPEV-QQYRSPSK] Rohini Rana 1SPIGYPEV7XVYGXYVI Irina Stefana 4L]WMSPSK]ERH1IXEFSPMWQ Harriet Taylor (IZIPSTQIRXEP2IYVSFMSPSK] Nadege Vernet 7XIQ'IPP&MSPSK]ERH (IZIPSTQIRXEP+IRIXMGW Matteo Villa 1SPIGYPEV-QQYRSPSK] 144 MRC National Institute for Medical Research Thibaut Brugat 4EVEWMXSPSK] Leona Gabrysova-QQYRSVIKYPEXMSR Eva Herrero 7XIQ'IPP&MSPSK]ERH (IZIPSTQIRXEP+IRIXMGW Simone Kunzelmann 4L]WMGEP&MSGLIQMWXV] Damian Perez-Mazliah 4EVEWMXSPSK] Ana Silva -QQYRI'IPP&MSPSK] Charles Sinclair -QQYRI'IPP&MSPSK] Darren Wight :MVSPSK] George Gentsch 7]WXIQW&MSPSK] Tim Ragan 1SPIGYPEV7XVYGXYVI Patricia Garcez 1SPIGYPEV2IYVSFMSPSK] Current funding sources 8LI1IHMGEP6IWIEVGL'SYRGMP16'MWXLITVMRGMTEPWSYVGISJVIWIEVGLJYRHMRK8LIFYHKIXGYVVIRXP]QTEMWWIXIZIV] ½ZI]IEVWJSPPS[MRKER-RWXMXYXI[MHIVIZMI[SJVIWSYVGIW8LMWVIZMI[XEOIWTPEGIEJXIVXLI½ZI]IEVP]TIIVVIZMI[GSRHYGXIHF] 16'6IWIEVGL&SEVHWSJXLITVSKVEQQIWSJXLIMRHMZMHYEP(MZMWMSRW 8LI-RWXMXYXIEPWSEXXVEGXWJYRHMRKWYTTSVXJVSQE[MHIVERKISJHMJJIVIRXEKIRGMIWMRGPYHMRKQIHMGEPVIWIEVGLGLEVMXMIW MRXIVREXMSREPWSYVGIWTEVXMGYPEVP]XLI)9ERHJVSQMRHYWXVMEPERHGSQQIVGMEPGSQTERMIW %7XEV16' %GEHIQ]SJ1IHMGEP7GMIRGIW %VXLVMXMW6IWIEVGL9/ BBSRC &SILVMRKIV-RKIPLIMQ Discovery Foundation EDCTP EMBO EPSRC )9 )YVS&MS-QEKMRK )YVSTIER6IWIEVGL'SYRGMP FEBS *SRHEXMSR0IHYU +IVQER6IWIEVGL'SYRGMP ,EVV]'VSWWPI]*SYRHEXMSR ,YQER*VSRXMIVW7GMIRGI4VSKVEQ 0EPSV*SYRHEXMSR*IPPS[WLMT 1EVWLEPP7GLSPEVWLMT*SYRHEXMSR 1IVMIY\%PPMERGI 16'8IGLRSPSK] MSD 2-, 4EVOMRWSR´W9/ 7ERS½4EWXIYV 7SYXLIVR%JVMGER'SRWSVXMYQJSVVIWIEVGL)\GIPPIRGI7%'36) 7[MWW2EXMSREP7GMIRGI*SYRHEXMSR ;IPPGSQI8VYWX MRC National Institute for Medical Research 145 Bibliography 1. +YXXIV](7,SPHIV%%ERH8I[EVM6 Sexual development in Plasmodium: lessons from functional analyses. PLOS Pathogens 8I 2. %FY(E]E%/LSOLE1/ERH>MQQIVQER0& The Hitchhiker’s guide to Xenopus genetics Genesis 50 3. 4. %HVSZIV11EVXSVIPP+1EVXMR769VSWIZ(/SREVIZ4:7ZIVKYR(- (EYVE<8IQYWWM4ERH4EWXSVI% The role of hydration in protein stability: comparison of the cold and heat unfolded states of Yfh1. Journal of Molecular Biology 417 %NIXYRQSFM;%3VMQEHIKYR%)&VS[R&.%JSPEFM2/3PEFM]M*%%RIXSV .-3QSOLSHMSR73WMRYWM/%OMRFEQM*37LSOYRFM;7SHIMRHI3ERH *IVRERHI^6I]IW( Haemoglobinuria among children with severe malaria attending tertiary care in Ibadan, Nigeria. Malaria Journal 11:336 5. %PQIMHE%61%VVS^1EHIMVE7*SRWIGE4IVIMVE(6MFIMVS,0EWVEHS6 4EGLRMW:ERH:IMKE*IVRERHIW, RET/GFR_ signals are dispensable for thymic T cell development In Vivo. PLOS ONE 7I 6. %QEQFYE2K[E%8IXXIL//%1ERWOI1+SQI^)WGSFEV27XI[EVX 0&(IIVLEOI1)'LIIWIQER-,2I[FSPH'-,SPHIV%%/RYITJIV) .ERLE3.EPPS[1'EQTMRS71EGMRRMW&/[MEXOS[WOM(4ERH'SR[E](. Population genomic scan for candidate signatures of balancing selection to guide antigen characterization in malaria parasites. PLOS Genetics 8I 7. %QTSJS;/&E]PSV2'SFI]7'S\2.(EZIW7)H[EVHW7*IVKYWSR2 +VSLQERR+,E]%/EX^./YPPEFYXV/0EQFIVX00IZERHS[WOM61MWLVE %'1SRXS%7MUYIMVE18EWLMVS1;EHHIPP%0;EMVEKOEV2;SSH. >EQFSR1ERH>LERK; -QTVSZMRKMR¾YIR^EZEGGMRIZMVYWWIPIGXMSR6ITSVXSJE;,3MRJSVQEP consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010. -R¾YIR^EERH3XLIV6IWTMVEXSV]:MVYWIW6 8. %RHIVWSR6,&VS[R2%1SLYR8.ERH1SSVQER%*1 Insights from cardiac development relevant to congenital defects and adult clinical anatomy. Journal of Cardiovascular Translational Research Epub ahead of print 9. %RHIVWSR6,'LEYHLV]&1SLYR8.&EQJSVXL7(,S]PERH(4LMPPMTW ,1;IFF71SSVQER%*.&VS[R2%ERH,IRHIVWSR(. Normal and abnormal development of the intrapericardial arterial trunks in humans and mice. Cardiovascular Research 95 10. %RHIVWSR6,1SLYR8.ERH1SSVQER%*1 What is a ventricle? Cardiology in the Young 21 11. %RKIPS/6ERG^)%4MQIRXIP(,YRHELP',ERRMFEP.*PIMWGLQERR% 4MGLPIV&ERH1EVKVMI8; %FMSTL]WMGEPWMKREXYVISJRIX[SVOEJ½PMEXMSRERHWIRWSV]TVSGIWWMRKMR mitral cells. Nature 488¯ 146 MRC National Institute for Medical Research 12. %VFSVI'0I[MW01ERH;IFF16 The kinetic mechanism of initiation by RepD as part of asymmetric, rolling circle plasmid unwinding. Biochemistry 51¯ 13. %VRZMK/ERH=SYRK( Non-coding RNA and its potential role in Mycobacterium tuberculosis pathogenesis. RNA Biology 9 14. &EIRE0STI^0%2SNMQE,ERH:MRGIRX.4 Integration of morphogen signalling within the growth regulatory network. Current Opinion in Cell Biology 24 15. &EKLIVM*EQ77VIIRMZEWER6&IVREVH4/RS[IV/'7IOMHS60SZIPP &EHKI6.YWX;ERH,EVPI]:6 Sox9 gene regulation and the loss of the XY/XX sex-determining mechanism in the mole vole Ellobius lutescens. Chromosome Research 20 16. &EPEWOEW26MFIMVS%4ERSZWOE.(IWWEYH)7EWEM24EKI/EVIR1 &VMWGSI.ERH6MFIW: Gene regulatory logic for reading the Sonic Hedgehog signaling gradient in the vertebrate neural tube. Cell 148 17. &ERGLIVIEY.4EWGYEP:ERH3´+EVVE% *VSQ-0XS-0XLII\TERHMRKWTIGXVYQSJERXMMR¾EQQEXSV] cytokines. Nature Immunology 13 18. &ERWEP%7&VEHPI]%7&MWLST/2/MERM%PMOLER7ERH*SVH& Chronic fatigue syndrome, the immune system and viral infection. Brain, Behavior, and Immunity 26 19. &EXPPI)ERH;MPOMRWSR(+ Molecular mechanisms of cell segregation and boundary formation in development and tumorigenesis. Cold Spring Harbor Perspectives in Biology 4E 20. &IPP%71MPPW.);MPPMEQW+4&VERRMKER.%;MPOMRWSR%.4EVOMRWSR8 0IEXLIVFEVVS[6.8EXI);,SPHIV%%ERH7QMXL(* Selective inhibitors of protozoan protein N-myristoyltransferases as starting points for tropical disease medicinal chemistry programs. PLoS Neglected Tropical Diseases 6I 21. &IP]EIZ22&MVz.%XLEREWEOMW(*IVRERHI^6I]IW(ERH4SXSGRMO%. Global transcriptional analysis of primitive thymocytes reveals EGGIPIVEXIHH]REQMGWSJ8GIPPWTIGM½GEXMSRMRJIXEPWXEKIW Immunogenetics 64 22. &IRXPI]7('SQEW-&V]ERX.1;EPOIV(7QMXL2,,EVVMW768LYVWXSR7 +EKRIY\7;SSH.%RXSRMS15YEMP1%+ILVI*%HIKFSPE6%4EVOLMPP. ERHHI.SRK&' The genome of Mycobacterium africanum West African 2 reveals a PMRIEKIWTIGM½GPSGYWERHKIRSQIIVSWMSRGSQQSRXSXLIM. tuberculosis complex. PLoS Neglected Tropical Diseases 6I 23. &IVPEXS(7XI[EVX.2I[XSR61EKPIRRSR+%1SRXM4*PMRHEPP%ERH 1YVTL]7 Evaluation of minichromosome maintenance protein 7 as a prognostic marker in canine cutaneous mast cell tumours. Veterinary and Comparative Oncology 10 Bibliography (cont.) 24. &IVVMQER.%ERH6SWIRXLEP4& Paraxial charge compensator for electron cryomicroscopy. Ultramicroscopy 116 25. &MERGS46ERH;IFF16 Helicase unwinding: active or merely perfect? Journal of Molecular Biology 420 26. &MIVMRKW6,IPPIR2/MWOMR2/RMTI0*SRWIGE%:4EXIP&1IPM%6SWI 1,ERREL1.ERH'EVXIV8 The interplay between the Rab27A effectors Slp4 a and MyRIP controls hormone-evoked Weibel-Palade body exocytosis. Blood 120 27. &PMWW8/EERK&/ERH>LYS1 The growth of Molecular Brain: impact factor is coming in 2013. Molecular Brain 5 28. &PSSQ'-+VELEQ'1&IVV]146;MPOMRWSR/%3RM86S^EOIEW*<Y >6SWWIPPS9VKIPP.'LEYWWEFIP(&ERGLIVIEY.4EWGYEP:0MTQER1 ;MPOMRWSR6.ERH3´+EVVE% Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLOS ONE 7:e46191 29. &SRH)0MERK*7ERHKVIR/.7QIH7}VIRWIR%&IVKQER4&VMKLIRXM 7%HEQW;'&IXIQEVMEQ7%6ERKEOE1<0ERKI';MPOMRWSR6. %RHIVWWSR.ERH0SVq/ 4PEWQEG]XSMHHIRHVMXMGGIPPWMR½PXVEXIXLIWOMRMRTSWMXMZIXYFIVGYPMRWOMR test indurations. Journal of Investigative Dermatology 132 30. &SVKSKRE'>EZEXXEVS)(I%RHVIE1+VMJ½R,1(IPP´3WXI:%^^MQSRXM &0ERHMRM114IL;04½WXIV,(SSVFEV.0ERHSPJS7ERH+EVMKPMS1 Characterization of beta papillomavirus E4 expression in tumours from Epidermodysplasia Verruciformis patients and in experimental models. Virology 423 31. &VIEY1%;MPWSR(;MPOMRWSR(+ERH<Y5 Chemokine and Fgf signalling act as opposing guidance cues in formation of the lateral line primordium. Development 139 32. &VMEXE4'LIR'=6EQSW%ERH+LIV^M6 Functional and molecular insights into KSRP Function in mRNA decay. Biochimica et Biophysica Acta Epub ahead of print 33. &VMH[IPP6EFF.-ERRY^^M'4EWXSVI%ERH&EVSRHIEY(4 Effector role reversal during evolution: the case of frataxin in Fe-S cluster biosynthesis. Biochemistry 51¯ 34. &VMWGSI.ERH6SLEXKM6 Singapore signalling: the 2012 hedgehog pathway cocktail. EMBO Reports 13 35. &VMWGSI.ERH7LEVTI. Genetics of system biology. Current Opinion in Genetics & Development 22 36. &VS[RPMI6.1MSWKI0%:EWWMPEOSW(7ZIRWWSR01'STI%ERH>EQS]WOE 6 0EGOSJXLITLSWTLEXEWI4842MRGVIEWIWEHLIWMSRSJQYVMRIVIKYPEXSV] 8GIPPWXSMQTVSZIXLIMVMQQYRSWYTTVIWWMZIJYRGXMSR Science Signaling 5VE 37. &YRRI]8()WTSWMXS(1EW(VSY\'0EQFIV)&E\IRHEPI6;1EVXMRW 1'SPI%7ZIVKYR((VMWGSPP4'ERH/EXER1 Structural and functional integration of the PLCa interaction domains critical for regulatory mechanisms and signaling deregulation. Structure 20¯ 38. &YVPMRE*1SVVMW'&ILVIRHX6;LMXI4ERH3JJIV. Simplifying native chemical ligation with an N-acylsulfonamide linker. Chemical Communications 48 39. &YVXI*&VS[R&.3VMQEHIKYR%)%NIXYRQSFM;%&EXXEKPME*)P]&/ %JSPEFM2/%XLEREWEOMW(%OMROYRQM*/S[SFEVM33QSOLSHMSR7 3WMRYWM/%OMRFEQM*37LSOYRFM;%7SHIMRHI3ERH*IVRERHI^6I]IW ( 7IZIVIGLMPHLSSHQEPEVMEW]RHVSQIWHI½RIHF]TPEWQETVSXISQI TVS½PIW PLOS ONE 7I 40. &YWLEXM2ERH&VMWGSI. Regulation of Neuronal Subtype Identity in the Vertebrate Neural Tube (Neuronal Subtype Identity Regulation). In: eLS. .SLR;MPI] 7SRW0XH 41. &Y\XSR67+VIIR.,YRX(1/ELVEQERSKPSY'7XETPIXSR16ERH 7[IIRI]24 Long range transcriptional control of virulence critical genes in Mycobacterium tuberculosis by nucleoid-associated proteins? Virulence 3¯ 42. 'EPPIV])14EVO'=<Y<>LY,7QMXL.'ERH8LSQWIR+, Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins. Open Biology 2 43. 'EWXMPPS7(1EXLIY%1EVMERM2'EVVIXIVS.0zTI^6uSW*0SZIPP&EHKI6 ERH7ERGLI^'IWTIHIW1 Novel transcriptional targets of the SRY-HMG box transcription factor SOX4 link its expression to the development of small cell lung cancer. Cancer Research 72 44. 'LERK%7QSPPIXX/0+STEYP//'LER&,ERH(EZMW)3 Mycobacterium tuberculosis H37Rv sigC is expressed from two promoters but is not auto-regulatory. Tuberculosis 48 45. 'LETQER81&SYPSG2&Y\XSR67'LYKL.0SYKLIIH/)%3WFSVRI 7%7E\X]&7QIVHSR7.8E]PSV(0ERH;LEPPI]( Substituted aminopyrimidine protein kinase B (PknB) inhibitors show activity against Mycobacterium tuberculosis. Bioorganic & Medicinal Chemistry Letters 22 46. 'LIR.1&S]6}XXKIV7(LEV27[IIRI]2&Y\XSR674SNIV* 6SWIROVERHW-ERH'SPI78 EspD is critical for the virulence-mediating ESX-1 secretion system in Mycobacterium tuberculosis. Journal of Bacteriology 194 47. 'LIYRK0=16M^^SXM/0SZIPP&EHKI6ERH0I8MWWMIV46 Pituitary phenotypes of mice lacking the Notch signalling ligand Deltalike 1 homologue (Dlk1). Journal of Neuroendocrinology Epub ahead of print MRC National Institute for Medical Research 147 Bibliography (cont.) 48. 'MH%VVIKYM%+EVMKPMS4/ERHE8ERH(SSVFEV. Oncogenic human papillomaviruses: high-risk human papillomaviruses: towards a better understanding of the mechanisms of viral transformation, latency and immune-escape. Open Virology Journal 6 58. (ENEW&EMPEHSV*&SRIZ&+EVGI^47XERPI]4+YMPPIQSX*ERH4ETEPSTYPY 2 microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons. Nature Neuroscience 15 49. 'SGUYIX.)PPMW4.-1ELEHIZEMEL7/%JJEVE2%:EMQER(ERH&YVKS]RI47 A genetic basis for a postmeiotic X versus Y chromosome intragenomic GSR¾MGXMRXLIQSYWI PLOS Genetics 8I 59. (I0SW6MSW4,EJRIV1ERH4EWXSVI% Explaining the length threshold of polyglutamine aggregation. Journal of Physics. Condensed Matter 24 50. 'SPPMRW'6ERH&PEGOQER1. Apicomplexan AMA1 in host cell invasion: a model at the junction? Cell Host & Microbe 10 51. 'SPY^^E-1EGHSREPH.87EHS[WOM1-8E]PSV;6ERH+SPHWXIMR6% Analytic Markovian rates for generalized protein structure evolution. PLOS ONE 7I 52. 'SQEW-&SVVIPP76SIX^IV%6SWI+1EPPE&/EXS1EIHE1+EPEKER. 2MIQERR7ERH+EKRIY\7 Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosisWXVEMRWMHIRXM½IWGSQTIRWEXSV]QYXEXMSRWMR62% polymerase genes. Nature Genetics 44 53. 'SRIWE&SXIPPE%1IMRXNIW+'SYWWIRW%/ZERHIV4PEW,+SPMEXL 67GLYX^'1SVIRS6I]IW61ILXE11EVXMRIEY%6;MPOMRWSR6. 'SPIFYRHIVW6ERH;MPOMRWSR/% 'SVXMGSWXIVSMHXLIVET]ZMXEQMR(WXEXYWERHMR¾EQQEXSV]G]XSOMRI TVS½PIMRXLI,-:8&MQQYRIVIGSRWXMXYXMSRMR¾EQQEXSV]W]RHVSQI (TB-IRIS). Clinical Infectious Diseases 55 54. 'SYWWIRW%/;MPOMRWSR6.,ERMJE=2MOSPE]IZWO]]:)POMRKXSR48-WPEQ /8MQQW41:IRXSR86&SXLEQPI]+,4EGOI+)(EVQEPMRKEQ1 (EZMHWSR621MPFYVR,.&EOIV0:&EVOIV6(1IMR'%&LE[6SWYR 02YEQEL6=SYRK(&(VSFRMI[WOM*%+VMJ½XLW'.ERH1EVXMRIEY%6 :MXEQMR(EGGIPIVEXIWVIWSPYXMSRSJMR¾EQQEXSV]VIWTSRWIWHYVMRK tuberculosis treatment. Proceedings of the National Academy of Sciences of the United States of America 109 148 60. (IGEVTIRXVMI*:IVRIX21ELEHIZEMEL7/0SRKITMIH+7XVIMGLIQFIVKIV )%ORMR7IMJIV-3NEVMOVI3%&YVKS]RI471IX^PIV+YMPPIQEMR'ERH 1MXGLIPP1. ,YQERERHQSYWI>*=KIRIWTVSHYGIEGSRWIVZIHXIWXMWWTIGM½G XVERWGVMTXIRGSHMRKE^MRG½RKIVTVSXIMR[MXLEWLSVXEGMHMGHSQEMRERH QSHM½IHXVERWEGXMZEXMSRTSXIRXMEP Human Molecular Genetics 21 61. (IRE\E1/EPEMX^MHSY1+EVIJEPEOM%%GLMQEWXSY%0EWVEHS61EIW8 ERH4EGLRMW: Maturation-promoting activity of SATB1 in MGE-derived cortical interneurons. Cell Reports 2¯ 62. (IZS]%&YRXSR7XEW]WL]R6/%8]FYPI[MG^:0.7QMXL%.,ERH*MWLIV )1' Genomically humanized mice: technologies and promises. Nature Reviews Genetics 13 63. (ME^%PSRWS.%KYEHS8;Y'74EPE^YIPSW.,SJQERR'+EVGI^4 +YMPPIQSX*0Y,'0YX^&+Y^QER1ERH+EPZI6STIVL- The CB1 cannabinoid receptor drives corticospinal motor neuron differentiation through the Ctip2/Satb2 transcriptional regulation axis. Journal of Neuroscience 32 64. (NSVHNIZMG7ERH(VMWGSPP4' Targeting VEGF signalling via the neuropilin co-receptor. Drug Discovery Today Epub ahead of print 65. (SSVFEV.5YMRX;&EROW0&VEZS-+7XSPIV1&VSOIV86ERH7XERPI]1% The biology and life-cycle of human papillomaviruses. Vaccine 30* 55. 'VEMK%++VEY+).ERWI'/E^YVE.;1MPRIV(&EVR[IPP.;8YVRIV+ ERH0ERKLSVRI. The role of animal models for research on severe malaria. PLOS Pathogens 8I 66. (SYWI',+VIIR.07EPKEHS477MQTWSR4.8LSQEW.'0ERKWPI]+ ,SPHIV%%8EXI);ERH'SXE) Regulation of the Plasmodium motor complex: phosphorylation of Myosin A Tail Interacting Protein (MTIP) loosens its grip on MyoA. Journal of Biological Chemistry 287 56. 'VY^02.YPMERS1%&YHY%.YPMERS0,SPHIV%%&PEGOQER1.ERH +EVGME'67 Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites. Malaria Journal 11:69 67. (YPI]%/4PSUYMR1.=)OWQSRH9%QQERR'+1IWWIV6.1]IVW0 ,EWIROVYK/.ERH/EWWMSXMW+ Negative impact of IFN-a on early host immune responses to retroviral infection. Journal of Immunology 189 57. HE'VY^02.YPMERS1%&YHY%.YPMERS0,SPHIV%%&PEGOQER1.ERH +EVGME'67 Extracellular ATP triggers proteolysis and cytosolic Ca2+ rise in Plasmodium berghei and Plasmodium yoelii malaria parasites. Malaria Journal 11: 68. )ZERW%0*EMEP8+MPGLVMWX1.(S[R8:EPPMIV04IHIVWIR6%;EVHPI*' ERH7QMXL.' Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells. PLOS ONE 7:e33346 MRC National Institute for Medical Research Bibliography (cont.) 69. *EVVS[6)+VIIR./EXMWQMXWSYPME>8E]PSV;6,SPHIV%%ERH1SPPS].) The mechanism of erythrocyte invasion by the malarial parasite, Plasmodium falciparum. Seminars in Cell & Developmental Biology 22 80. +IQQE7+MSZERM7&VMRHMWM18VMTEPHM4&VSKM77EZMRM0*MSVMRM- 2SZIPPMRS)&YXMRM7'EQTMERM+4IR^S1ERH&PEGOQER1. Quinolylhydrazones as novel inhibitors of Plasmodium falciparum serine protease PfSUB1. Bioorganic & Medicinal Chemistry Letters 22 70. *MRRI]&%7GL[IMKLSJJIV)2EZEVVS2yI^0&qRq^IGL'&EVSRI* ,YKLIW')0ERKER7%0S[I/04SPPMXX%=1SYVES7E(7LIEVHS[R 72EWL+&7QMXLIVW26IMWI7SYWE'8]FYPI[MG^:0.ERH;EXWSR74 CLEC-2 and Syk in the megakaryocytic/platelet lineage are essential for development. Blood 119 81. +MHISR,4;MPOMRWSR/%6YWXEH863RM8+YMS,7LIVQER(6 :SVHIVQIMIV,16SFIVXWSR&(=SYRK(&ERH;MPOMRWSR6. Bioinformatic and empirical analysis of novel hypoxia-inducible targets of the human antituberculosis T cell response. Journal of Immunology 189 71. *MZMER,YKLIW%,SYKLXSR.ERH(EZMW) Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid. Microbiology 158 72. *VEGGEPZMIVM(8MFIVXM14ERHMRM%&SREXM0ERH4ETEPIS) Functional annotation of the mesophilic-like character of mutants in a cold-adapted enzyme by self-organising map analysis of their molecular dynamics. Molecular BioSystems 8 82. +MPGLVMWX1. From expression cloning to gene modeling: the development of Xenopus gene sequence resources. Genesis 50 83. +MPGLVMWX1.ERH4SPPIX2 Databases of gene expression in Xenopus development. Methods in Molecular Biology 917 84. +MRHIW01EXWYM,%GLMVSR61SLYR8,S7=ERH+EVHMRIV, Comparison of ex-vivo high-resolution episcopic microscopy with in-vivo JSYVHMQIRWMSREPLMKLVIWSPYXMSRXVERWZEKMREPWSRSKVETL]SJXLI½VWX trimester fetal heart. Ultrasound in Obstetrics & Gynecology 39 73. *VIMXEWHS6SWjVMS%40EQF87TIRGI47XITLIRW60ERK%6SIVW% 1YPPIV;3´+EVVE%ERH0ERKLSVRI. IL-27 promotes IL-10 production by effector Th1 CD4+ T cells: a critical mechanism for protection from severe immunopathology during malaria infection. Journal of Immunology 188 85. +zQI^+EZMVS10SZIPP&EHKI6*IVRjRHI^%ZMPqW*ERH0EVE4I^^M) The vascular stem cell niche. Journal of Cardiovascular Translational Research 5 74. *VIMXEWHS6SWEVMS%4ERH0ERKLSVRI. T cell-derived IL-10 and its impact on the regulation of host responses during malaria. International Journal for Parasitology 42 86. +zQI^+EZMVS1:7GSXX')7IWE]%/1EXLIY%&SSXL7+EPMGLIX'ERH 0SZIPP&EHKI6 Betacellulin promotes cell proliferation in the neural stem cell niche and stimulates neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 109 75. *VMHL:ERH6MXXMRKIV/ The tandem CARDs of NOD2: intramolecular interactions and recognition of RIP2. PLOS ONE 7I 76. *YOYHE84VEXXS*7GLMQIRXM.'8YVRIV.1%'EQIVMRM3XIVS6(ERH ,}}K' Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis. PLOS Genetics 8I 77. +EPMERS1.SLRWSR&*1]IVW6)PPMW.(ERMIPW6ERH>EQFSR1 *EXEPGEWIWSJMR¾YIR^E%,2MRGLMPHVIRMRWMKLXWJVSQ[LSPI genome sequence analysis. PLOS ONE 7:e33166 78. +ERXOI87VMWOERXLEVENEL77EHS[WOM1ERH0I]7' IgB kinase regulation of the TPL-2/ERK MAPK pathway. Immunological Reviews 246 79. +IEGL8.7XIQTPI(0ERH>MQQIVQER0& Genetic analysis of Xenopus tropicalis. Methods in Molecular Biology 917 87. +SRGEPZIW:&VERRMKER.%;LEPPI](%RWIPP/,7E\X]&,SPHIV%% ;MPOMRWSR%.8EXI);ERH0IEXLIVFEVVS[6. Discovery of Plasmodium vivax N-myristoyltransferase inhibitors: screening, synthesis, and structural characterization of their binding mode. Journal of Medicinal Chemistry 55 88. +SR^EPI^]1IVGLERH.%>EVEKS^E'SRXVIVEW6+YEHEVVEQE1IHMRE 6,IPKYIVE6ITIXXS%'6MZIVE+YXMIVVI^7'IVRE'SVXIW.*7ERXSW %VKYQIHS0ERH'S\6% Evaluation of the cell growth of mycobacteria using Mycobacterium smegmatis mc2 155 as a representative species. Journal of Microbiology 50 89. +SSHI(/ERH)PKEV+ Capturing the regulatory interactions of eukaryote genomes. &VMI½RKWMR*YRGXMSREP+IRSQMGWEpub ahead of print 90. +VERX.1ELEHIZEMEL7//LMP47ERKVMXLM126S]S,(YGO[SVXL. 1G'EVVI].6:ERHI&IVK.06IRJVII1&8E]PSV;)PKEV+'EQIVMRM3XIVS 6(+MPGLVMWX1.ERH8YVRIV.1 Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature 4879 MRC National Institute for Medical Research 149 Bibliography (cont.) 91. +VMJ½R,;Y>1EVRERI6(I[EV:1SPMNR%5YMRX;:ER,SSJ' 7XVY]J*'SPEY&.IROMRW(ERH(SSVFEV. E4 antibodies facilitate detection and type-assignment of active HPV infection in cervical disease. PLOS ONE 7I 92. +VM^IROSZE.%OLXEV7,YQQIVMGL,8SQPMRWSR%%WERXI)%;IRFSVR %*M^IX.4SYPXIV1;MWIQER*/*MWLIV)1'8]FYPI[MG^:0.&VERHRIV7 'SPPMRKI.ERH0PS]H7) Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice. Proceedings of the National Academy of Sciences of the United States of America 109 93. +VSSQ,'8ERH&MWLST/2 The tale of xenotropic murine leukemia virus-related virus. Journal of General Virology 93 94. +VSSQ,'8;EVVIR%=2IEP()ERH&MWLST/2 No evidence for infection of UK prostate cancer patients with XMRV, BK virus, Trichomonas vaginalis or human papilloma viruses. PLOS ONE 7I 95. +Y7/IPP]+;ERK<*VIROMIP87LIZGLMO:)ERH4MGOIVWKMPP6; Solution structure of homology region (HR) domain of type II secretion system. Journal of Biological Chemistry 287 96. +YMSPM70SZIPP&EHKI6ERH8YVRIV.1% Error-prone ZW pairing and no evidence for meiotic sex chromosome inactivation in the chicken germ linI PLOS Genetics 8I 97. +YXXIV](7*IVKYWSR(.44SYPMR&<Y>7XVEWGLMP9/PST37SP]EOSZ0 7ERHVMRM71&VEH](2MIHYW^]RWOM'%.ERWI'.,SPHIV%%8SFMR%&ERH 8I[EVM6 A putative homologue of CDC20/CDH1 in the malaria parasite is essential for male gamete development. PLOS Pathogens 8I 98. +YXXIV](74SYPMR&*IVKYWSR(.47^SSV&;MGOWXIEH&'EVVSPP40 6EQEOVMWLRER'&VEH](4EX^I[MX^)17XVEWGLMP97SP]EOSZ0+VIIR.0 7MRHIR6)8SFMR%&,SPHIV%%ERH8I[EVM6 A unique protein phosphatase with kelch-like domains (PPKL) in Plasmodium modulates ookinete differentiation, motility and invasion. PLOS Pathogens 8I 99. ,EWLEWL2.SLRWSR%0ERH'LE67 Topoisomerase II- and condensin-dependent breakage of MEC1ATRsensitive fragile sites occurs independently of spindle tension, anaphase, or cytokinesis. PLOS Genetics 8I 100. ,EYFIVX(0M.7EZIPMIZ%'EP^EWGME87YXXIV)1IX^PIV&/EMWIV( 8]FYPI[MG^:0.ERH;IGOFIGOIV+ Vav1 GEF activity is required for T cell mediated allograft rejection. Transplant Immunology 26 101. ,IHKIXLSVRI/ERH;IFF16 Fluorescent SSB as a reagentless biosensor for single-stranded DNA. Methods in Molecular Biology 922 150 MRC National Institute for Medical Research 102. ,IRHIVWSR67EPM%&EOIV10'EVVEKLIV&(IZOSXE&(S[RMRK/, )KIPQER),*IRK>*VERO.+VMKSVMIJJ2.MERK;0YHXOI7.1IHEPME3 4IRG^IO4%6SWIRXLEP4&6SWWQERR1+7GLQMH1*7GLV}HIV+*7XIZIR %'7XSOIW(0;IWXFVSSO.(;VMKKIVW;=ERK,=SYRK.&IVQER,1 'LMY;/PI][IKX+.ERH0E[WSR'0 3YXGSQISJXLI½VWXIPIGXVSRQMGVSWGST]ZEPMHEXMSRXEWOJSVGIQIIXMRK Structure 20 103. ,MRHPI]'%PM*1G(S[IPP+'LIRK/.SRIW%+YMPPIQSX*ERH4LMPTSXX % 4SWXXVERWPEXMSREPQSHM½GEXMSRSJ2KRHMJJIVIRXMEPP]EJJIGXWXVERWGVMTXMSR of distinct targets to regulate the balance between progenitor maintenance and differentiation. Development 139 104. ,SHWSR(.7GLEIJJIV16SQERS2*SRXEREYH40EJSRX'&MVOIRWXSGO .1SPMRS*'LVMWXMER,0SGOI].'EVQMKREG(*IVRERHI^*YIRXI10I 8MWWMIV4ERH1SPPEVH4 Existence of long-lasting experience-dependent plasticity in endocrine cell networks. Nature Communications 3:605 105. ,SPHIV%%1SLH6MH^YER1%ERH+VIIR.0 'EPGMYQHITIRHIRXTVSXIMROMREWIERHGEPGMYQ¾Y\IWMRXLIQEPEVME parasite. Microbes and Infection 14¯ 106. ,SPPMRK[SVXL('ERHIP%12MGEWXVS+1EVXMR76&VMEXE4+LIV^M6ERH 6EQSW% KH domains with impaired nucleic acid binding as a tool for functional analysis. Nucleic Acids Research 40 107. ,SPQ0%GOPERH+0)H[EVHW16&VIGOIRVMHKI6%7MQ6&ERH3JJIV. 'LIQMGEPPEFIPPMRKSJEGXMZIWIVYQXLMSIWXIVTVSXIMRWJSVUYERXM½GEXMSR Immunobiology 217 108. ,SYKLXSR.8S[RWIRH';MPPMEQW%66SHKIVW%6ERH0;EPOIV/& &}XXKIV)'7TVMRKIV&ERH(EZMW)3 An important role for Mycobacterium tuberculosis UvrD1 in pathogenesis and persistence apart from its function in nucleotide excision repair. Journal of Bacteriology 194 109. ,Y,:SWW.>LERK+&YGL]4>YS8;ERK0;ERK*>LSY*;ERK+ 8WEM''EPHIV0+EQFPMR7.>LERK0(IYFIP:>LSY&7OILIP..ERH >LSY4 A human antibody recognizing a conserved epitope of H5 hemagglutinin FVSEHP]RIYXVEPM^IWLMKLP]TEXLSKIRMGEZMERMR¾YIR^E,2ZMVYWIW Journal of Virology 86 110. ,YRX(17[IIRI]241SVM0;LEPER6,'SQEW-2SVQER0'SVXIW8 %VRZMK/&(EZMW)37XETPIXSR16+VIIR.ERH&Y\XSR67 Long range transcriptional control of an operon necessary for virulencecritical ESX-1 secretion in Mycobacterium tuberculosis. Journal of Bacteriology 194 111. ,YVX%''LSXTMXE]EWYRSRHL8'S\2.(ERMIPW6*V]%1+YFEVIZE0: ,E]HIR*+,YM(7,YRKRIW30EGOIRF]%0MQ;1IMNIV%4IRR' 8EWLMVS19]IOM81ERH>EQFSR1 %RXMZMVEPVIWMWXERGIHYVMRKXLIMR¾YIR^E%,2TERHIQMGTYFPMG health, laboratory, and clinical perspectives. The Lancet Infectious Diseases 12 Bibliography (cont.) 112. -UFEP1)WWIR7'<MES,&VSSOIW71&VS[R-,ERH1G'EYPI].; Selection of variant viruses during replication and transmission of H7N1 viruses in chickens and turkeys. Virology 433¯ 123./PEWWIR/1EVXMRIEY%6;MPOMRWSR6.'SSOI+'SYVXRI]%4ERH,MGOWSR 1 The effect of tenofovir on vitamin D metabolism in HIV-infected adults is dependent on sex and ethnicity. PLOS ONE 7:e44845 113. -WEEGWSR;IGLWPIV);ERK56SFIVXW-4EKPMEVYPS).EGOWSR( 9RXIVWTIVKIV''SPIQER2+VMJ½R,ERH(SSVFEV. Reconstruction of human papillomavirus type 16-mediated early-stage neoplasia implicates E6/E7 deregulation and the loss of contact inhibition in neoplastic progression. Journal of Virology 86 124./PIMRNYRK.ERH*VEXIVREPM* Urea-water solvation forces on prion structures. Journal of Chemical Theory and Computation 8 114. .EJOMRW%%FY(E]E%2SFPI%>MQQIVQER0&ERH+YMPPI1 Husbandry of Xenopus tropicalis. Methods in Molecular Biology 917 115. .YRKQMGLIP7'PETTIVXSR.%0PS]H.,EVM*.7T]GLIV'4EZMG00M.,EMVI 0*&SREPPM10EVWIR(,0YOEW'0YOEW.1EGQMPPER(2MIPWIR107XYGOM 1ERH7QIVHSR7. The molecular basis of ATM-dependent dimerization of the Mdc1 DNA damage checkpoint mediator. Nucleic Acids Research 40 116. /EPWHSVJ&7OSPMQS[WOE/,7GVMFE8.(E[WSR6(LIHE/;SSH/ ,SJQIMWXIV.,ERIOSQ;%0ERKI'ERH;MPOMRWSR6. Relationship between chemokine receptor expression, chemokine levels and HIV-1 replication in the lungs of persons exposed to Mycobacterium tuberculosis. European Journal of Immunology Epub ahead of print 117. /ETYWXMR%7XITERSZE:%RMSP2'MRIW(&4SPMEOSZ%=EVSZSM70IFIHIZE 8;EMX66]^LEOSZ+4EVJ]SRSZE=+YVWO]==EREKMWE[E,1MREWLOMR1 &IEFIEPEWLZMPPM6:SVSXRMOSZ%&SFMO%ERH8OEGLYO: Fibulin-5 binds urokinase-type plasminogen activator and mediates urokinase-stimulated `1-integrin-dependent cell migration. Biochemical Journal 443 118. /EXWMQMXWSYPME>ERH8E]PSV;6 Coarse-grained simulation of myosin-V movement. Computational and Mathematical Methods in Medicine 119. /LER71%PM6%WM2ERH1SPPS].) Active actin gels. Communicative & integrative biology 5 120. /MGLIZE%&SPPIRFEGL8;EVXPMGO3.YPMGLIV*ERH+SR^EPI^+EMXER1 Investigating the principles of morphogen gradient formation: from tissues to cells. Current Opinion in Genetics & Development 22¯ 121. /MGLIZE%'SLIR1ERH&VMWGSI. Developmental pattern formation: insights from physics and biology. Science 338 122. /MXEQYVE//MWLM-XEOYVE'8WYFSM87EXS7/MXE/3LXE2ERH1M^YWLMQE 2 Autophagy-related Atg8 localizes to the apicoplast of the human malaria parasite Plasmodium falciparum. PLOS ONE 7I 125./PIMRNYRK.7GSXX;64%PPMWSR.6ZER+YRWXIVIR;*ERH*VEXIVREPM* Implicit solvation parameters derived from explicit water forces in largescale molecular dynamics simulations. Journal of Chemical Theory and Computation 8 126./PMQSZ%-+EVXIR66YWWIPP'&EVV-+&IWWIPEEV8+(ERMIPW6)RKIPLEVHX 3++VSLQERR+-XEQYVE7/IPWS%1G'EYPI].3HEKMVM87QMXL( 8EWLMVS1<Y<;IFF]6;ERK(=I>=YIPSRK7>LERK;ERH'S\2 WHO recommendations for the viruses to be used in the 2012 7SYXLIVR,IQMWTLIVI-R¾YIR^E:EGGMRIITMHIQMSPSK]ERXMKIRMGERH KIRIXMGGLEVEGXIVMWXMGWSJMR¾YIR^E%,2THQ%,2ERH& MR¾YIR^EZMVYWIWGSPPIGXIHJVSQ*IFVYEV]XS7ITXIQFIV Vaccine 30 127./WMSRHE37EZIPMIZ%/SGLP66ETPI].*EVSYHM17QMXL+EVZMR.) ;YP½RK'6MXXMRKIV/'EVXIV8ERH8]FYPI[MG^:0. Mechanism and function of Vav1 localization in TCR signaling. Journal of Cell Science 125 128.0EPPIQERH40IFER2/YR^IPQERR7'LEPSMR07IVTIVWY),;IFF16 &EVQER8ERH0MSRRI' Transient kinetics of aminoglycoside phosphotransferase(3v)-IIIa reveals a potential drug target in the antibiotic resistance mechanism. FEBS Letters 586¯ 129.0EWSRHIV)+VIIR.0'EQEVHE+8EPEFERM,,SPHIV%%0ERKWPI]+ERH %PERS4 The Plasmodium falciparum schizont phospho-proteome reveals extensive phosphatidylinositol and cAMP-Protein Kinase A signalling. Journal of Proteome Research 11¯ 130.0E[XSR.&VYKEX8=EQ<=6IMH%&SILQI93XXS84EMR%.EGOWSR% &IVVMQER1'YRRMRKLEQ(4VIMWIV4ERH0ERKLSVRI. Characterization and gene expression analysis of the cir multi-gene family of Plasmodium chabaudi chabaudi (AS). BMC Genomics 13 131.0I(VqEY++EVGME'EQTQER]06EFEHjR1%*IVVSRLE88S^IV7 &VMWGSI.ERH1EVXM) Canonical BMP7 activity is required for the generation of discrete neuronal populations in the dorsal spinal cord. Development 139 132.0I8MWWMIV46,SHWSR(.0EJSRX'*SRXEREYH47GLEIJJIV1ERH1SPPEVH 4 Anterior pituitary cell networks. Frontiers in Neuroendocrinology 33 133.0II&6M^^SXM//[SR(7/MQ7=3L7)TWXIMR(.7SR==SSR.&EIO/ ERH.ISRK= Direct transcriptional regulation of Six6 is controlled by SoxB1 binding to a remote forebrain enhancer. Developmental Biology 366 MRC National Institute for Medical Research 151 Bibliography (cont.) 134. 0II/8ER.1SVVMW1&6M^^SXM/,YKLIW.'LIEL47*IPUYIV*0MY<4MPX^ 70SZIPP&EHKI6ERH8LSQEW45 Congenital hydrocephalus and abnormal subcommissural organ development in Sox3 transgenic mice. PLOS ONE 7I 144. 0S[I(1&ERKERM21ILXE160ERK(16SWWM%+;MPOMRWSR/% ;MPOMRWSR6.ERH1EVXMRIEY%6 A novel assay of antimycobacterial activity and phagocytosis by human neutrophils. Tuberculosis Epub ahead of print 135. 0IWGVSEVX*1SLYR81IMPLEG71&IRRIXX1ERH&YGOMRKLEQ1 %PMRIEKIXVIIJSVXLIZIRSYWTSPISJXLILIEVXGPSREPEREP]WMWGPEVM½IW controversial genealogy based on genetic tracing. Circulation Research 111 145. 0S[I(16IHJSVH47;MPOMRWSR6.3´+EVVE%ERH1EVXMRIEY%6 Neutrophils in tuberculosis: friend or foe? Trends in Immunology 33 136. 0M(6SQEMR+*PEQEV%0(YPYG((YPPEIVW10M<,>YVE[WOM7 &SWUYIX24EPYGOE%/0I+VERH63´+EVVE%>YVE[WOM+&ERGLIVIEY. ERH3L7 Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells. Journal of Experimental Medicine 209 137. 0M,'SPPEHS1:MPPEWERXI%1EXLIY%0]RGL'.'EREQIVS16M^^SXM/ 'EVRIMVS'1EVXMRI^+:MHEP%0SZIPP&EHKI6ERH7IVVERS1 p27Kip1 directly represses Sox2 during embryonic stem cell differentiation. Cell Stem Cell 11 138. 0M50M20I8MWWMIV4+VEXXER(6ERH/IVQER/ Miniaturized electrochemical immunosensor for label-free detection of growth hormone. Electroanalysis 24 139. 0MFIVPIW(%8IMGLQERR7%&ELEV-&EWXSPPE9&PSSQ.&SVRFIVK&EYIV) 'SP[IPP0.HI/SRMRK%4.(SOLSP]ER2:)GLEZI.)PSJWWSR%+IVPSJJ(0 +SPHWXIMR6%+VELRIR.%,SPHIV180EORIV'0EVXMPPSX20SZIPP7' 2E]PSV+4IVMGE84SPPSGO((4YTOS86IKER06SKIV%6YFMRWXIMR2 7LEOLRSZMGL)7N}PERHIV/7YR]EIZ78IYJIP%-8LSVRI.08LSVRXSR.; ;IMRVIMGL(1ERH;LIPER7 The interface of protein structure, protein biophysics, and molecular . evolution. Protein Science 21 140. 0MR(',+YS50YS.>LERK.2KY]IR/'LIR18VER8(VERW½IPH 4.&VS[R74,SY^I.:MQSPVEXERE1.MES<=;ERK=&MVHWEPP2.1ERH 7[EQMREXL+ -HIRXM½GEXMSRERHTLEVQEGSPSKMGEPGLEVEGXIVM^EXMSRSJQYPXMTPIEPPSWXIVMG binding sites on the free fatty acid 1 receptor. Molecular Pharmacology 82 141. 0MR=4<MSRK<;LEVXSR7%1EVXMR76'SSQFW4.:EGLMIVM7+ 'LVMWXSHSYPSY);EPOIV4%0MY.7OILIP..+EQFPMR7.,E]%.(ERMIPW67 ERH1G'EYPI].; )ZSPYXMSRSJXLIVIGITXSVFMRHMRKTVSTIVXMIWSJXLIMR¾YIR^E%,2 hemagglutinin. Proceedings of the National Academy of Sciences 109¯ 142. 0SIFFIVQERR.7GLRSIPPIV'8LSVRXSR,(YVERX07[IIRI]247GLYMNW 13´+EVVE%.SLERWWSR'ERH3TIRWLE[4. IL-10 regulates viral lung immunopathology during acute respiratory syncytial virus infection in mice. PLOS ONE 7I 143. 0STIW6:IVLI]ZER;MNO22IZIW+ERH4EGLRMW: Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum. Proceedings of the National Academy of Sciences of the United States of America 109: 152 MRC National Institute for Medical Research 146. 0YHFVSSO01&IVREVH4&EKLIVM*EQ76]ER.7IOMHS6;MPLIPQ( 0SZIPP&EHKI6ERH,EVPI]:6 )\GIWW(%<PIEHWXS<=SZSXIWXMGYPEVHMWSVHIVSJWI\HIZIPSTQIRX (DSD) in mice by inhibiting steroidogenic factor-1 (SF1) activation of the testis enhancer of SRY-box-9 (Sox9). Endocrinology 153 147. 0]GIXX7.&EMPPMI+'SYPXIV)&LEXX7/IPPEQ41G'EYPI].;;SSH.02 &VS[R-,4]FYW3+0IMKL&VS[R%.ERH'SQFEXMRK7[MRI-R¾YIR^E -RMXMEXMZI'37-'SRWSVXMYQ )WXMQEXMRKVIEWWSVXQIRXVEXIWMRGSGMVGYPEXMRK)YVEWMERW[MRIMR¾YIR^E viruses. Journal of General Virology 93 148. 1EGLE.8IMGLQERSZE67EXIV%;IPPW(8PETEOSZE8>MQQIVQER0ERH /V]PSZ: Deep ancestry of mammalian X chromosome revealed by comparison with the basal tetrapod Xenopus tropicalis. BMC Genomics 13:315 149. 1EKPIRRSR+%ERH(SSVFEV. The biology of papillomavirus latency. Open Virology Journal 6 150. 1ES'7LYOPE10EVVSY]1EYQYW+(M\*0/IPPI]0%7XIVRFIVK1. 7SFVEP&;ERHHI'EVZEPLS047 Functional assignment of Mycobacterium tuberculosis proteome revealed by genome-scale fold-recognition. Tuberculosis Epub ahead of print 151. 1EVXMRS04IRRIPP7/IPP]+&YM888/SXMO/SKER37QIVHSR7.(VEOI %*'YVV]7ERH'SRXI16 Analysis of the interaction with the hepatitis C virus mRNA reveals an alternative mode of RNA recognition by the human La protein. Nucleic Acids Research 40¯ 152. 1EVX]RSKE&(VIGLWIP(ERH+YMPPIQSX* Molecular control of neurogenesis: a view from the mammalian cerebral cortex. Cold Spring Harbor Perspectives in Biology 4:a008359 153. 1EWXIPMG&*VIMXEWHS6SWEVMS%4:IPHLSIR16IREYPH.'.EVVE; 7TSREEW%16SIX]RGO77XSGOMRKIV&ERH0ERKLSVRI. IL-22 protects against liver pathology and lethality of an experimental blood-stage malaria infection. Frontiers in Immunology 3:00085 154. 1EXLIY%'SPPEHS1;MWI'1ERXIVSPE0'IOEMXI08]I%.'EREQIVS 1&YNERHE07GLIHP%'LIEL/7)7OSXLIMQ6-0SXLI6%0zTI^HI 1YREMR%&VMWGSI.7IVVERS1ERH0SZIPP&EHKI6 Oncogenicity of the developmental transcription factor Sox9. Cancer Research 72 Bibliography (cont.) 155. 1G)ZS]'6)'PSIXI61PPIV&7GLVGL%'ZER,IPHIR4(+EKRIY\7 ;EVVIR61ERH+I]ZER4MXXMYW2' Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints. PLOS ONE 7:e30593 156. 1IMRXNIW+7OSPMQS[WOE/,;MPOMRWSR/%1EXXLI[W/8EHSOIVE6 'SRIWE&SXIPPE%7IPHSR66ERKEOE1<6IFI/4ITTIV(.1SVVSRM' 'SPIFYRHIVW61EEVXIRW+ERH;MPOMRWSR6. Corticosteroid-modulated immune activation in the tuberculosis MQQYRIVIGSRWXMXYXMSRMR¾EQQEXSV]W]RHVSQI American Journal of Respiratory and Critical Care Medicine 186 157. 1IPM%'EVXIV81G'SVQEGO%,ERREL1.ERH6SWI10 Antibody alone is not a stimulator of exocytosis of Weibel-Palade bodies from human endothelial cells. Transplantation 94¯ 158. 1IRSR647SSRK(HI'LMEVE',SPX16%RMPOYQEV2ERH4EWXSVI% The importance of serine 776 in Ataxin-1 partner selection: A FRET analysis. 7GMIRXM½G6ITSVXW 2:919 159. 1IX^EOSTMER)0MR;7EPQSR(MZSR1(ZMRKI,%RHIVWWSR))VMGWSR. 4IVPQERR8;LMXWIXX.%&IVXSRI4ERH%RK70 Genome-wide characterization of Foxa2 targets reveals upregulation SJ¾SSVTPEXIKIRIWERHVITVIWWMSRSJZIRXVSPEXIVEPKIRIWMRQMHFVEMR dopaminergic progenitors. Development 139 160. 1MGLIP104ERK(.,EUYI7*=4SXSGRMO%.4IRRMRKXSR(.ERH,E]HE] %' Interleukin 7 (IL-7) selectively promotes mouse and human IL-17– producing ab cells. Proceedings of the National Academy of Sciences of the United States of America 109 161. 1MRKYMPPSR'2MWLMQSXS7;SSH7:IRHVIPP)+MFWSR&VS[R..ERH 0SKER143 Hox genes regulate the onset of Tbx5 expression in the forelimb. Development 139 162. 1SLYR8.ERH;IRMRKIV;. Generation of volume data by episcopic three-dimensional imaging of embryos. Cold Spring Harbor Protocols 7 163. 1SLYR8.ERH;IRMRKIV;. Embedding embryos for high-resolution episcopic microscopy (HREM). Cold Spring Harbor Protocols 7 164. 1SLYR8.ERH;IRMRKIV;. )QFIHHMRKIQFV]SWJSVITMWGSTMG¾YSVIWGIRGIMQEKIGETXYVMRK)*-' Cold Spring Harbor Protocols 7 165 1SLYR8.ERH;IRMRKIV;. Episcopic three-dimensional imaging of embryos. Cold Spring Harbor Protocols 7 166. 1SPPEVH4,SHWSR(.0EJSRX'6M^^SXM/ERH(VSYMR. A tridimensional view of pituitary development and function. Trends in Endocrinology and Metabolism 23 167. 1SSH]47QMXL1)&6]ER'4'LYHEWEQE:&EOIV.61SPPS].ERH 'EHHMGO7 Bromomaleimide-linked bioconjugates are cleavable in mammalian cells. Chembiochem : a European journal of chemical biology 13 168. 1SSR6;,EPP.6ERKOYXM*,S=7%PQSRH21MXGLIPP+,4EMR% ,SPHIV%%ERH&PEGOQER1. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes. Proceedings of the National Academy of Sciences 110 169. 1SWW(/6IQEVUYI).*EFIV&;'EZEREKL(6%VRSX()8LSQEW%; ERH,SPHIV%% Plasmodium falciparum 19-kilodalton merozoite surface protein 1 174WTIGM½GERXMFSHMIWXLEXMRXIVJIVI[MXLTEVEWMXIKVS[XLin vitro can inhibit MSP1 processing, merozoite invasion and intracellular parasite development. Infection and Immunity 80 170. 2IEV]181SLYR8.ERH&VIGOIRVMHKI6% Hypoxia, long QT interval and sudden infant death syndrome (SIDS). Disease Models & Mechanisms Epub ahead of print 171. 2IREWLIZE8%'EVXIV8ERH1EWLERSZ+- %YXSQEXMGXVEGOMRKSJMRHMZMHYEPQMKVEXMRKGIPPWYWMRKPS[QEKRM½GEXMSR HEVO½IPHQMGVSWGST] Journal of Microscopy 246 172. 2IZIW+7LEL110MSHMW4%GLMQEWXSY%(IRE\E16SEPJI+7IWE]% ;EPOIV1'ERH4EGLRMW: The LIM homeodomain protein Lhx6 regulates maturation of interneurons and network excitability in the mammalian cortex. Cerebral Cortex Epub ahead of print 173. 2I[QER)6/RIEPI++6EZIPPM6&+/EVYTTEWEQ]12INEHEWP*/8E]PSV -%ERH1G+IILER.) Large multimeric assemblies of nucleosome assembly protein and histones revealed by small-angle X-ray scattering and electron microscopy. Journal of Biological Chemistry 287 174. 2MERK12(SWWIL%2HME]I/7EKRE1+VIKSV]:+SYHMEF](,E]% ERH(MST31 7IRXMRIPWYVZIMPPERGIJSVMR¾YIR^EMR7IRIKEP¯ Journal of Infectious Diseases 20677 175. 2MGEWXVS++EVGME1E]SVEP1*,SPPMRK[SVXL(/IPP]+1EVXMR76&VMEXE 4+LIV^M6ERH6EQSW% Noncanonical G recognition mediates KSRP regulation of let-7 biogenesis. Nature Structural & Molecular Biology 19¯ 176. 2XWIOLI11EXXLI[W/;SPWOI.&EHVM1;MPOMRWSR/%;MPOMRWSR6. 7XYVVSGO)(ERH1E]SWM&1 7GMIRXM½GPIXXIV%G7(/42EGIX]PWIV]PEWTEVX]PP]W]PTVSPMRIERH Galectin-3 levels in tuberculous pericardial effusion: implications for pathogenesis and prevention of pericardial constriction. Heart 98 177. O’Garra A Regulation of the immune response to pathogens - Part 1 of 2 -R']XSOMRIW-RXIVGIPPYPEVQIHMEXSVWVIKYPEXMRKLSWXHIJIRWI(The Biomedical & Life Sciences Collection),IRV]7XI[EVX8EPOW0XH0SRHSR MRC National Institute for Medical Research 153 Bibliography (cont.) 178. O’Garra A Regulation of the immune response to pathogens - Part 2 of 2 -R']XSOMRIW-RXIVGIPPYPEVQIHMEXSVWVIKYPEXMRKLSWXHIJIRWI (The Biomedical & Life Sciences Collection),IRV]7XI[EVX8EPOW0XH0SRHSR 179. 3´+EVVE%ERH4EQIV) Host pathogens. Current Opinion in Immunology 24 180. 3RM8+MHISR,4&ERKERM28WIOIPE67IPHSR6;SSH/;MPOMRWSR/% +SPMEXL683XXIRLSJJ8,ERH;MPOMRWSR6. Risk factors associated with indeterminate interferon gamma responses in the assessment of latent tuberculosis infection in a high incidence environment. Clinical and Vaccine Immunology 19 181. 3RM8+MHISR,4&ERKERM28WIOIPE67IPHSR6;SSH/;MPOMRWSR/% +SPMEXL683XXIRLSJJ8,1ERH;MPOMRWSR6. Smoking, BCG and employment and the risk of tuberculosis infection in HIV-infected persons in South Africa. PLOS ONE 7I 182. 3RM88WIOIPE6/[E^E&1ERNI^M0&ERKERM2;MPOMRWSR/%'SIX^II( ERH;MPOMRWSR6. A recent HIV diagnosis is associated with non-completion of isoniazid preventive therapy in an HIV-infected cohort in Cape Town. PLOS ONE 7I 183. 3]EPPSR.%TMX^,1MKYIP%PMEKE-8MQSJIIZ/*IVVIMVE0ERH7EPIGOIV- Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors. Developmental Biology 369¯ 184. 4EGEV]),EEW1%;MPHRIV,%^^EVIPPM6&IPP(1%FVSYW(2ERH +YMPPIQSX* Visualization and genetic manipulation of dendrites and spines in the mouse cerebral cortex and hippocampus using in utero electroporation. Journal of Visualized Experiments e4163 185. 4EGEV])1EVX]RSKE&ERH+YMPPIQSX* 'VYGMEP½VWXWXITWXLIXVERWGVMTXMSREPGSRXVSPSJRIYVSRHIPEQMREXMSR Neuron 74 186. 4EPQE'IVHE*%YKIV''VE[JSVH(.,SHKWSR%''6I]RSPHW7.'S[IPP ./7[MJX/%('EMW3:]OPMGO]0'SVVMI.)8ERH3KHIR( New caged neurotransmitter analogs selective for glutamate receptor sub-types based on methoxynitroindoline and nitrophenylethoxycarbonyl caging groups. Neuropharmacology 63¯ 187. 4ERHMRM%*SVRMPM%*VEXIVREPM*ERH/PIMRNYRK. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics. FASEB Journal 26 188. 4EVEMR/1E^YVMIV2&VSRGLEMR3&SVHE]''EFSGLIXXI4'LIWRIEY% 'SPS^^E+)P=EOSYFM;,EQHEGLI.0SGOIV1+MPGLVMWX1.4SPPIX2ERH 4IVVSR1 A large scale screen for neural stem cell markers in Xenopus retina. Developmental Neurobiology 72 154 MRC National Institute for Medical Research 189. 4EWXSVI% Physics and biology of neurodegenerative diseases. Journal of Physics. Condensed Matter 24 190. 4EWXSVI%ERH8IQYWWM4 Protein aggregation and misfolding: good or evil? Journal of Physics. Condensed Matter 24 191. 4EWXSVI%ERH8IQYWWM4% The two faces of Janus: functional interactions and protein aggregation. Current Opinion in Structural Biology 22 192. 4EXIP%,EVOIV21SVIMVE7ERXSW0*IVVIMVE1%PHIR/8MQQMW.*SWXIV /+EVIJEPEOM%4EGLRMW4%RHVI[W4)RSQSXS,1MPFVERHX.4EGLRMW: 'SPIW1'/MSYWWMW(ERH:IMKE*IVRERHIW, Differential RET signaling pathways drive development of the enteric lymphoid and nervous systems. Science Signaling 5:ra55 193. 4EX[EVHLER%'EVE^S.1'EVVEKLIV&,IRHIVWSR6,I]QERR.&,MPP ).IRWIR+.0EKIVWXIHX-0E[WSR'00YHXOI7.1EWXVSREVHI(1SSVI ;.6SWIQER%6SWIRXLEP47SV^ERS'377ER^+EVGME)7GLIVIW7,; 7YFVEQERMEQ7;IWXFVSSO.;MRR17[IHPS[.6ERH/PI][IKX+. Data management challenges in three-dimensional EM. Nature Structural & Molecular Biology 19 194. 4EYPW77QMXL7*ERH)PKEV+ Lens development depends on a pair of highly conserved Sox21 regulatory elements. Developmental Biology 365 195. 4EY[IPW/;MPPMEQW801SVVMW/0.SRGOLIIVI;:ERHIVWXIIR%/IPP]+ 7GL]QOS[MX^.6SYWWIEY*4EWXSVI%7IVTIPP0'ERH&VSIVWIR/ Structural basis for increased toxicity of pathological A`42:A`40 ratios in Alzheimer’s disease. Journal of Biological Chemistry 287 196. 4IEVWSR'7MPZE%ERH7IHHSR& Exogenous amino acids are essential for interleukin-7 induced CD8 T cell growth. PLOS ONE 7:e33998 197. 4IHVIyS74MWGS.40EVVSY]1EYQYW+/IPP]+ERHHI'EVZEPLS047 Mechanism of feedback allosteric inhibition of ATP phosphoribosyltransferase. Biochemistry 51¯ 198. 4ITTIV(.1EVEMW7&LEMNII*;MPOMRWSR6.(I%^IZIHS:ERH1IMRXNIW + Assessment at antiretroviral clinics during TB treatment reduces loss to follow-up among HIV-infected patients. PLOS ONE 7I 199. 4MGSRI(ERH8IQYWWM4% Dissimilar sweet proteins from plants: oddities or normal components? Plant Science 195 200. 4MXX.1&PEROPI]71G7LERI,ERH3´+EVVE% Vaccination against tuberculosis: how can we better BCG? Microbial Pathogenesis Epub ahead of print Bibliography (cont.) 201. 4MXX.17XEZVSTSYPSW)6IHJSVH47&IIFI%1&ERGVSJX+.=SYRK(&ERH 3´+EVVE% Blockade of IL-10 signaling during bacillus Calmette-Guérin vaccination enhances and sustains Th1, Th17, and innate lymphoid IFN-aand IL-17 responses and increases protection to Mycobacterium tuberculosis infection. The Journal of Immunology 189 202. 4SPPSGO((8LMPXKIR+ERH+SPHWXIMR6% Amino acid coevolution induces an evolutionary Stokes shift. Proceedings of the National Academy of Sciences of the United States of America 109)) 203. 4SPWLEOSZ:-)PMWIIZ&(&MVHWEPP&ERH*VSPSZE0= Structure and dynamics in solution of the stop codon decoding N-terminal domain of the human polypeptide chain release factor eRF1. Protein Science 21 204. 4SVXIZMR(:ME0))YQ7ERH=SYRK( Natural killer cell are recruited during pulmonary tuberculosis and ex-vivo, their response to mycobacteria vary between healthy human donors in association with KIR haplotype. Cellular Microbiology 14 205. 5YMRX;.IROMRW(1SPMNR%7XVYMNO0ZERHI7ERHX1(SSVFEV.1SPW. :ER,SSJ',EVHX/7XVY]J*ERH'SPEY& One virus one lesion - individual components of CIN lesions contain a WTIGM½G,4:X]TI Journal of Pathology 227 206. 6EFEHjR1%'E]YWS.0I(VqEY+'VY^'&EV^M14SRW7&VMWGSI.ERH 1EVXu) Jagged2 controls the generation of motor neuron and oligodendrocyte progenitors in the ventral spinal cord. Cell Death and Differentiation 19¯ 207. 6ERKEOE1<+MHISR,4;MPOMRWSR/%4EM11[ERWE/EQFE½P[I. 1EEVXIRW++P]RR.6&SYPPI%*MIPHMRK/+SPMEXL68MXYW61EXLII7ERH ;MPOMRWSR6. No discriminatory value of interferon release added to smear negative HIV-tuberculosis algorithms. European Respiratory Journal 39 208. 6ERKEOE1<+MHISR,4;MPOMRWSR/%4EM11[ERWE/EQFEJ[MPI. 1EEVXIRW++P]RR.6&SYPPI%*MIPHMRK/+SPMEXL68MXYW61EXLII7ERH ;MPOMRWSR6. Interferon release does not add discriminatory value to smear-negative HIV-tuberculosis algorithms. European Respiratory Journal 39 209. 6ERKEOE1<;MPOMRWSR/%+P]RR.60MRK(1IR^MIW(1[ERWE /EQFEJ[MPI.*MIPHMRK/;MPOMRWSR6.ERH4EM1 Predictive value of interferon-arelease assays for incident active tuberculosis: a systematic review and meta-analysis. Lancet Infectious Diseases 12 210. 6ERKEOE1<;MPOMRWSR6.+P]RR.6&SYPPI%ZER'YXWIQ++SPMEXL6 1EXLII7ERH1EEVXIRW+ Effect of antiretroviral therapy on the diagnostic accuracy of symptom WGVIIRMRKJSVMRXIRWM½IHXYFIVGYPSWMWGEWI½RHMRKMRE7SYXL%JVMGER,-: clinic. Clinical Infectious Diseases 55 211. 6EX^MRKIV*&VYGOWGL[EMKIV,;MWGLIRFEVX14EVWGLEPO&*IVRERHI^ 6I]IW(0EKPIV,-RHVE%+VERMRKIV;;MROPIV7/VMWLRE7ERH 6EQLEVXIV1 Rapid diagnostic algorithms as a screening tool for tuberculosis: an assessor blinded cross-sectional study. PLOS ONE 7:e49658 212. 6IIW1+SVFE'HI'LMEVE'&YM888+EVGME1E]E1(VEOI%PI\* 3OE^E[E,4EWXSVI%7ZIVKYR(ERH'LIR=Y; Solution model of the intrinsically disordered polyglutamine tractbinding protein-1. Biophysical Journal 102 213. 6MH^YER1%11SSR6;/RYITJIV)&PEGO7,SPHIV%%ERH+VIIR.0 Subcellular location, phosphorylation and assembly into the motor complex of GAP45 during Plasmodium falciparum schizont development. PLOS ONE 7:e33845 214. 6MWGS%HIP*VIWRS'1EQFSP%%PWMRE&IEYGLEQT(1EG/IR^MI/* =ERK,8&EVFIV(*1SVGIPPI'%VXLYV.7'0I]7'%VHEZMR'ERH 'YIRHE% p38aand p38bkinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation. Proceedings of the National Academy of Sciences of the United States of America 109 215. 6SFIVXWSR&(%PXQERR(&EVV]'&MWLEM&'SPI7(MGO8(YRGER/ (]I')LVX7)WQEMP,*P]RR.,EJRIV6,ERHPI]+,ERIOSQ;ZER ,IPHIR4/ETPER+/EYJQERR7,)/MQ40MIRLEVHX'1M^VELM:6YFMR )7GLRETTMRKIV(7LIVQER(8LSPI.:ERHEP3;EP^P+;EVRIV( ;MPOMRWSR6ERH=SYRK( Detection and treatment of subclinical tuberculosis. Tuberculosis 92 216. 6SKIX/&IR%HHM%1EQFSPI(IQE%+ERXOI8=ERK,8.ER^IR. 1SVVMGI2%FFSXX(ERH0I]7' IKK2 regulates TPL-2 activation of ERK-1/2 MAP kinases by direct phosphorylation of TPL-2 serine 400. Molecular and Cellular Biology 32 217. 6SQERS(&VERHQIMIV&MVKMX(7YR=&8VIRXLEQ(6ERH-VZMRK1 Orientation of the N-terminal lobe of the myosin regulatory light chain MRWOIPIXEPQYWGPI½FIVW Biophysical Journal 102 218. 6YIGOIV%7LIE1,EGOIXX*7YEVI^',MVWX)1%1MPYXMRSZMG/ ;MXLIVW1EVXMRI^'ERH&PEGOQER1. Proteolytic activation of the essential parasitophorous vacuole cysteine protease SERA6 accompanies malaria parasite egress from its host erythrocyte. Journal of Biological Chemistry 287 219. 7EHS[WOM1- Prediction of protein domain boundaries from inverse covariances. Proteins: Structure, Function, and Bioinformatics 81¯ 220. 7EHS[WOM1-ERH8E]PSV;6 Evolutionary inaccuracy of pairwise structural alignments. Bioinformatics 28 MRC National Institute for Medical Research 155 Bibliography (cont.) 221. 7EIR^6%)WWIR7'&VSSOIW71-UFEP1;SSH.02+VIRJIPP&8 1G'EYPI].;&VS[R-,ERH+SK.6 Quantifying transmission of highly pathogenic and low pathogenicity ,2EZMERMR¾YIR^EMRXYVOI]W PLOS ONE 7:e45059 233. 7GLYX^'-WQEMP>4VS\IRSW'.1EVEMW7&YVXSR6/IR]SR'1EEVXIRW +;MPOMRWSR6.ERH1IMRXNIW+ Burden of antituberculosis and antiretroviral drug-induced liver injury at a secondary hospital in South Africa. South African Medical Journal 102 222. 7ELEF>7YHEVWLER760MY<>LERK=/MVMP]YO%/EQSRNSL'17MQMG: (EM=&]IVW7;(SSVFEV.7YTV]RS[MG^*%ERH7GLPIKIP6 Quantitative measurement of human papillomavirus type 16 E5 oncoprotein levels in epithelial cell lines by mass spectrometry. Journal of Virology 86 234. 7IMFX.%VQERX30I(MKEVGLIV%'EWXVS(6EQIWL:.SYVRSX0 +YMPPIQSX*:ERHIVLEIKLIR4ERH&SYWGLIX8 Expression at the imprinted Dlk1-Gtl2 locus is regulated by proneural genes in the developing telencephalon. PLOS ONE 7I 223. 7EPEQEX/1SYHNSY1'LETYMW.,IV^SK0.EYQEMR)&qVMRKYI:6I^EIM ,4EWXSVI%0EYHI,ERH(VSR1 Integrity of helix 2-helix 3 domain of the PrP protein is not mandatory for prion replication. Journal of Biological Chemistry 287 235. 7LITTEVH34PEXXRIV*6YFMR%7PIRHIV%0MRILER.1&VERHRIV7 8]FYPI[MG^:0.*MWLIV)1'ERH;MWIQER*/ Altered regulation of tau phosphorylation in a mouse model of down syndrome aging. Neurobiology of Aging 33I¯I 224. 7ERHLY+&EXXEKPME*)P]&/%XLEREWEOMW(1SRXS]E6:EPIRGME8+MPQER 6,)ZERW'%*VMIHPERH.7*IVRERHI^6I]IW(ERH%KVERSJJ(( Discriminating active from latent tuberculosis in patients presenting to community clinics. PLOS ONE 7:e38080 236. 7LITTEVH3;MWIQER*/6YTEVIPME%8]FYPI[MG^:0.ERH*MWLIV)1' Mouse models of aneuploidy. 7GMIRXM½G;SVPH.SYVREP2012 225. 7ERIGOE%ERH*VMGOIP)1 Use and abuse of dendritic cells by Toxoplasma gondii. Virulence 3 226. 7ERJIPMGI(%HVSZIV11EVXSVIPP+4EWXSVI%ERH8IQYWWM4% Crowding versus molecular seeding: NMR studies of protein aggregation in hen egg white. Journal of Physics. Condensed Matter 24 227. 7EVOEV60IRHIVW0;MPOMRWSR/%;MPOMRWSR6.ERH2MGSP14 Modern lineages of Mycobacterium tuberculosisI\LMFMXPMRIEKIWTIGM½G patterns of growth and cytokine induction in human monocyte-derived macrophages. PLOS ONE 7I 228. 7EWEM2ERH&VMWGSI. Primary cilia and graded Sonic Hedgehog signaling. Wiley Interdisciplinary Reviews: Developmental Biology 1¯ 156 237. 7MQISRM-+MPGLVMWX1.+EVVIXX2%VQMWIR.ERH+YVHSR.& Widespread transcription in an amphibian oocyte relates to its reprogramming activity on transplanted somatic nuclei. Stem cells and development 21 238. 7MQSRIXXE*+IWXIVQERR21EVXMRIX/>&SRMSXXS18MWWMIVIW47IHHSR &ERH&SYVKISMW' -RXIVPIYOMRMR¾YIRGIW*3<4'(VIKYPEXSV]8GIPPWTIVMTLIVEP homeostasis. PLOS ONE 7:e36596 239. 7M^EVSZ%0EQIVW;,1SLYR8.&VS[R2%%RHIVWSR6,ERH 1SSVQER%*1 Three-dimensional and molecular analysis of the arterial pole of the developing human heart. Journal of Anatomy 220 229. 7EWWIPPM:4EGLRMW:ERH&YVRW%. The enteric nervous system. Developmental Biology 366 240. 7OSPMQS[WOE/,6ERKEOE1<1IMRXNIW+4ITTIV(.7IPHSR61EXXLI[W /;MPOMRWSR6.ERH;MPOMRWSR/% Altered ratio of IFN-a/IL-10 in patients with drug resistant Mycobacterium tuberculosis and HIV- tuberculosis Immune 6IGSRWXMXYXMSR-R¾EQQEXSV]7]RHVSQI PLOS ONE 7:e46481 230. 7GLEET-%8)KLMEMER*HIW+ISVKIW%ERH:IMKIP' )JJIGXSJIRZIPSTITVSXIMRWSRXLIQIGLERMGEPTVSTIVXMIWSJMR¾YIR^E virus. Journal of Biological Chemistry 287 241. 7QMXL0.7XETPIXSR16&Y\XSR67ERH+VIIR. Structure-function relationships of the Mycobacterium tuberculosis transcription factor WhiB1. PLOS ONE 7I 231. 7GLEIJIV%8ERH1EVKVMI8; Psychophysical properties of odor processing can be quantitatively described by relative action potential latency patterns in mitral and tufted cells. Frontiers in Systems Neuroscience 6:0030 242. 7QSPPIXX/07QMXL/1/ELVEQERSKPSY'%VRZMK/&&Y\XSR67ERH (EZMW)3 Global analysis of the regulon of the transcriptional repressor LexA, a key component of the SOS response in Mycobacterium tuberculosis. Journal of Biological Chemistry 287 232. 7GLYWXIV18VIMXWGLOI7/MPEVY71SPPS].,EVQIV2.ERH7XIMRFIVK+ Myosin-5, kinesin-1 and myosin-17 cooperate in secretion of fungal chitin synthase. EMBO Journal 31 243. 7RIPKVSZI6.'SVRIVI11)H[EVHW0(EKK&/IIFPI.6SHKIVW% 0]SRKE()7XI[EVX+6=SYRK(&;EPOIV&ERH,YWWIPP8 OX40 ligand fusion protein delivered simultaneously with the BCG vaccine provides superior protection against murine Mycobacterium tuberculosis infection. Journal of Infectious Diseases 205 MRC National Institute for Medical Research Bibliography (cont.) 244. 7SPIV2'VEIWGY'8+EPPE].*VETEVX=11ERWY](6E]REP&&EPHEGGM+ 4EWXSVI%,YERK1)ERH:IVRMW0 A S-adenosylmethionine methyltransferase-like domain within the essential, Fe-S containing yeast protein Dre2. FEBS Journal 279 245. 7TIRGI4..EVVE;0IZ]42ELVIRHSVJ;ERH0ERKLSVRI. Mosquito transmission of the rodent malaria parasite Plasmodium chabaudi. Malaria Journal 11 246. 7TIRGI4.ERH0ERKLSVRI. T cell control of malaria pathogenesis. Current Opinion in Immunology 24 247. 7TIVPMRK83PHEO1;EPGL6YGOLIMQ&;MGOIRLEYWIV'(SSVFEV. 4½WXIV,1EPING^]O11ENI[WOM7/IEXIW%'ERH7QSPE7 Human papillomavirus type 8 interferes with a novel C/EBP`-mediated mechanism of keratinocyte CCL20 chemokine expression and langerhans cell migration. PLOS Pathogens 8I 248. 7TSREEW%1&IP]EIZ2*EPGO,ERWIR14SXSGRMO%ERH0ERKLSVRI. 8VERWMIRXHI½GMIRG]SJHIRHVMXMGGIPPWVIWYPXWMRPEGOSJE1IVS^SMXI 7YVJEGI4VSXIMRWTIGM½G'(8GIPPVIWTSRWIHYVMRKTIEOPlasmodium chabaudi blood-stage infection. Infection and Immunity 80 249. 7XETPIXSR167QMXL0.,YRX(1&Y\XSR67ERH+VIIR. Mycobacterium tuberculosis WhiB1 represses transcription of the essential chaperonin GroEL2. Tuberculosis 92 250. 7XIMRLEYWIV10&EMPI]%47IR]S7)+YMPPIVQMIV'4IVPWXIMR87+SYPH%4 0II68ERH0IGLIRI'4 1YPXMMWSXSTIMQEKMRKQEWWWTIGXVSQIXV]UYERXM½IWWXIQGIPPHMZMWMSR and metabolism. Nature 481 251. 7XMIKPMX^&,EMVI0*(MOMG-ERH6MXXMRKIV/ Structural analysis of SHARPIN, a subunit of a large multi-protein E3 ubiquitin ligase, reveals a novel dimerization function for the pleckstrin homology superfold. Journal of Biological Chemistry 287 256. 7YPPMZER//PSIWW.5MER'&IPP(,E]%0MR=4ERH+Y= ,MKLXLVSYKLTYXZMVYWTPEUYIUYERXMXEXMSRYWMRKE¾EXFIHWGERRIV Journal of Virological Methods 179 257. 7YR=&EO&7GLSIRQEOIVW2ZER8VSXWIRFYVK%743SWXHMNO;:SWLSP 4'EQFVMHKI);LMXI./PI8MWWMIV4+LEVEZ]7211EVXMRI^&EVFIVE.4 7XSOZMW&VERXWQE;,:YPWQE8/IQTIVW1.4IVWERM0'EQTM-&SRSQM 1&IGO4IGGS^4>LY,(EZMW81),SOOIR/SIPIKE%'7(IP&PERGS (+6ERKEWEQM..6YMZIROEQT'%00EVSW.*./VMIO1/ERX7+&SWGL '%.&MIVQEW^26%TTIPQER(MNOWXVE21'SVWWQMX)4,SZIRW+'. 4IVIMVE%1(YRRIR.8H;EHI1+&VIYRMRK1,,IRRIOEQ6' 'LEXXIVNII/(EXXERM18;MX.1ERH&IVREVH(. Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nature Genetics 44¯ 258. 8EQYVM%9HSW6IMW1ERH+SPHWXIMR6% Using site-wise mutation-selection models to estimate the distribution SJWIPIGXMSRGSIJ½GMIRXWJVSQTL]PSKIRIXMGHEXE Genetics 90 259. 8EQYVM%9HSW6IMW1ERH+SPHWXIMR6% )WXMQEXMRKXLIHMWXVMFYXMSRSJWIPIGXMSRGSIJ½GMIRXWJVSQTL]PSKIRIXMG data using sitewise mutation-selection models. Genetics 190 260. 8ER'0+YREVEXRI.0EM('EVXLEKIRE0;ERK5<YI=>5YIO07 (SSVFEV.&EGLIPIVMI*8LMIVV]*ERH&IPPERKIV7 HPV-18 E2^E4 chimera: 2 new spliced transcripts and proteins induced by keratinocyte differentiation. Virology 429 261. 8EXXIVQYWGL77OMRRIV.%'LEYWWEFIP(&ERGLIVIEY.&IVV]141G2EF *;3´+EVVE%8E]PSV+4ERH&ERKLEQ'61 7]WXIQWFMSPSK]ETTVSEGLIWVIZIEPEWTIGM½GMRXIVJIVSRMRHYGMFPI signature in HTLV-1 associated myelopathy. PLOS Pathogens 8I 262. 8E]PSV;6.SRIW(8ERH7EHS[WOM1- Protein topology from predicted residue contacts. Protein Science 21 263. 8E]PSV;61SVPI]6/VEWEZMR%+VIKSV]0;MPOMRWSR(+ERH4SPMEOSZ % A mechanical model of cell segregation driven by differential adhesion. PLOS ONE 7I 252. 7XMIKPMX^&1SVVMW(EZMIW%'/SPMSTSYPSW1+'LVMWXSHSYPSY)ERH 6MXXMRKIV/ LUBAC synthesizes linear ubiquitin chains via a thioester intermediate. EMBO Reports 13 264. 8IQYWWM4% The good taste of peptides. Journal of Peptide Science 18 253. 7XMIKPMX^&6MXXMRKIV/ERH,EMVI0* Crystallization of SHARPIN using an automated two-dimensional grid screen for optimization. Acta Crystallographica Section F 68 265. 8IQYWWM4%ERH/[ERK;. New insights into the characteristics of sweet and bitter taste receptors. International Review of Cell and Molecular Biology 291 254. 7XS]I.4 Studies of endogenous retroviruses reveal a continuing evolutionary saga. Nature Reviews Microbiology 10 266. 8IVVMIRXI.+IVIX]77;EXEREFI%WEOE8+SR^EPI^5YIZIHS6ERH ;MPOMRWSR(+ Signalling from hindbrain boundaries regulates neuronal clustering that patterns neurogenesis. Development 139 255. 7XYGOM(1EPPE&,SWXIXXPIV7,YRE8*IPHQERR.=IFSEL1ERY(&SVVIPP 7*IRRIV0'SQEW-'SWGSPPk1ERH+EKRIY\7 Two new rapid SNP-typing methods for classifying Mycobacterium tuberculosis complex into the main phylogenetic lineages. PLOS ONE 7I 267. 8LMPXKIR+ERH+SPHWXIMR6% Assessing predictors of changes in protein stability upon mutation using self-consistency. PLOS ONE 7:e46084 MRC National Institute for Medical Research 157 Bibliography (cont.) 268. 8LSQTWSR'-0EGOIRF]%(ERMIPW671G'EYPI].;4IVI]EWPSZ( &VSFIVK)/1IMNIV%ERH>EQFSR1' )ZEPYEXMSRSJMR¾YIR^EZMVYWERXMZMVEPWYWGITXMFMPMX]XIWXMRKMR)YVSTI 6IWYPXWJVSQXLI½VWXI\XIVREPUYEPMX]EWWIWWQIRXI\IVGMWI Journal of Clinical Virology 56¯ 269. 8LSVTI4,(MXXQEV.'ERH6SXLWXIMR6 ScreenTroll: a searchable database to compare genome-wide yeast screens. Database 2012FEW 270. 8LSVTI4,ERH6SXLWXIMR6 Visualizing global effects of the DNA damage response. Nature Cell Biology 14 271. 8MQSJIIZ/.SP];,EHNMIGSRSQSY(ERH7EPIGOIV- 0SGEPM^IHRIXVMRWEGXEWTSWMXMSREPGYIWXSGSRXVSPPE]IVWTIGM½G targeting of photoreceptor axons in Drosophila. Neuron 75 272. 8SQMREKE1/SNMQE,=SOSXE)2EOEQSVM6%RWSR17LMQQIR8ERH 3M[E/ The calcium-induced mechanical change in the neck domain alters the activity of plant myosin XI. Journal of Biological Chemistry 287 273. 8SWIPERH'44S[IPP&ERH;IFF16 ATPase cycle and DNA unwinding kinetics of RecG helicase. PLOS ONE 7I 274. 8VIRX7'EWWERS8&IHWI+3NEVMOVI3%,YQF]8ERH(EZMIW; Altered serotonergic function may partially account for behavioral IRHSTLIRSX]TIWMRWXIVSMHWYPJEXEWIHI½GMIRXQMGI Neuropsychopharmacology 37 275. 8VIRX7(IRRIL]%6MGLEVHWSR,3NEVMOVI3%&YVKS]RI47,YQF]8 ERH(EZMIW; 7XIVSMHWYPJEXEWIHI½GMIRXQMGII\LMFMXIRHSTLIRSX]TIWVIPIZERXXS %XXIRXMSR(I½GMX,]TIVEGXMZMX](MWSVHIV Psychoneuroendocrinology 37 276. 8YSQIPE77EPS:8VMTEXLM7/'LIR>0EYVMPE/+YTXE&cMN}83MOEVM0 7XSGOMRKIV&0mLHIWQmOM,ERH0ELIWQEE6 -HIRXM½GEXMSRSJIEVP]KIRII\TVIWWMSRGLERKIWHYVMRKLYQER8LGIPP differentiation. Blood 119II 277. 8YVXSR.7XVSQ10ERKLEQ7(EXXERM1ERH0I8MWWMIV4 Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to Combined Pituitary Hormone (I½GMIRG] Clinical Endocrinology 76: 278. 9VV]>'LEQFIVW)7<]WXVEOMW)(MQIPSI76MGLEVHW(*+EFV]äSZj 0'LVMWXIRWIR.+YTXE%7EKPERM7&YWL%3´+EVVE%&VS[R>ERH ,E[V]PS[MG^'1 The role of 1_,25-dihydroxyvitamin D3 and cytokines in the promotion of distinct Foxp3+and IL-10+ CD4+T cells. European Journal of Immunology 42 279. ZERHIR&SSQ.,IMHIV(1EVXMR764EWXSVI%ERH1YIPPIV.; 3’-Phospho-adenosine-5’-phosphosulphate (PAPS) synthases - naturally JVEKMPIIR^]QIWWTIGM½GEPP]WXEFMPMWIHF]RYGPISXMHIFMRHMRK Journal of Biological Chemistry 287 158 MRC National Institute for Medical Research 280. ZERHIV:VMIW)'SPPMRW4.:EGLMIVM7+<MSRK<0MY.;EPOIV4%,EMVI0* ,E]%.7GLYXXIR13WXIVLEYW%(1)1EVXMR76&SYGLIV'%&7OILIP.. ERH+EQFPMR7. ,2TERHIQMGMR¾YIR^EZMVYWVIWMWXERGISJXLI-6 neuraminidase mutant explained by kinetic and structural analysis. PLOS Pathogens 8I 281. :qPI^*SVX1ERH1EVKVMI8; Cortical circuits: layer 6 is a gain changer. Current Biology 2266 282. :IVRIX21ELEHIZEMEL7/)PPMW4.HI6SSMN(+ERH&YVKS]RI47 Spermatid development in XO male mice with varying Y chromosome short arm gene content: evidence for a Y gene controlling the initiation of sperm morphogenesis. Reproduction 144 283. :MHEOM18MZSHEV7(SYPKIVEOM/8]FYPI[MG^:/IWWEVMW24EGLRMW:ERH /EVEKSKISW( Rac1-dependent cell cycle exit of MGE precursors and GABAergic interneuron migration to the cortex. Cerebral Cortex 22 284. :MRGIRX,%,IRHIVWSR'%6EKER8.+EV^E+EVGME%'EV]4(+S[IVW (11EPJSMW1(VMWGSPP4'7SFSXX*ERH'EPPEKLER%. Characterization of Vibrio cholerae Hfq provides novel insights into the role of the Hfq C-terminal region. Journal of Molecular Biology 420 285. :MRGIRX.4ERH1EKII8 Tiki casts a spell on Wnt. Cell 149 286. :MVKS2*IVRERHS'&MKKI&ERH,YWFERHW4 Evolvable physical self-replicators. %VXM½GMEP0MJI 18 287. :MWS*&LEXXEGLEV]E(/SRK=+MPGLVMWX1.ERH/LSOLE1/ Exon capture and bulk segregant analysis: rapid discovery of causative mutations using high-throughput sequencing. BMC Genomics 13:649 288. :SVHIVQIMIV,1,I[MRWSR6+;MPOMRWSR6.;MPOMRWSR/%+MHISR ,4=SYRK(&ERH7EQTWSR70 Conserved immune recognition hierarchy of mycobacterial PE/PPE proteins during infection in natural hosts. PLOS ONE 7:e40890 289. ;EPOIV2*'PEVO733RM8%RHVIY28I^IVE07MRKL77EVEMZE0 4IHIVWIR&/IPP](08VII.%(´%VQMIRXS.11IMRXNIW+1EYVM*% ;MPPMEQW%;MPOMRWSR6.*VMIHPERH.7ERH)POMRKXSR48 Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases. American Journal of Respiratory and Critical Care Medicine 185 290. ;EWMPI[WOM7'EPHIV0.+VERX8ERH6SWIRXLEP4& (MWXVMFYXMSRSJWYVJEGIKP]GSTVSXIMRWSRMR¾YIR^E%ZMVYWHIXIVQMRIH by electron cryotomography. Vaccine 291. ;EWMPI[WOM7/EVIPMRE(&IVVMQER.%ERH6SWIRXLEP4& %YXSQEXMGQEKRM½GEXMSRHIXIVQMREXMSRSJIPIGXVSRGV]SQMGVSWGST] images using apoferritin as a standard. Journal of Structural Biology 180 292. ;IMRIV&+SQI^.:MGXSV8';EVVIR617PSYXWO]%4PMOE]XMW&&4SWI] .)ZER,IPHIR4(+I]ZER4MXXMYW2'/SILVWIR17MWO47XSPXI';LMXI .+EKRIY\7&MVVIR&,YRK(1YVVE]1ERH+EPEKER. Independent large scale duplications in multiple M. tuberculosis lineages overlapping the same genomic region. PLOS ONE 7I 293. ;MKLX(.&SYGLIVMX:'2EHIV1%PPIR(.8E]PSV-%ERH&MWLST/2 The gammaretroviral p12 protein has multiple domains that function during the early stages of replication. Retrovirology 9:0083 294. ;MPLIPQ'8YVRIV.):ER7RMGO.ERH7XSGOMRKIV& The many lives of IL-9: a question of survival? Nature Immunology 13 295. ;MPOMRWSR/%1IMRXNIW+7IPHSR6+SPMEXL6ERH;MPOMRWSR6. Immunological characterisation of an unmasking TB-IRIS case. South African Medical Journal 102 296. ;MPOMRWSR/%8SVSO1)7GL[ERHIV7ERH1IMRXNIW+ HIV-associated tuberculosis 2012. Clinical and Developmental Immunology 2012:950964 297. ;MPOMRWSR6. Human genetic susceptibility to tuberculosis: time for a bottom-up approach? Journal of Infectious Diseases 205 304. =SYRK+6)OWQSRH97EPGIHS6%PI\STSYPSY07XS]I.4ERH/EWWMSXMW + 6IWYVVIGXMSRSJIRHSKIRSYWVIXVSZMVYWIWMRERXMFSH]HI½GMIRXQMGI Nature 491¯ 305. =SYRK+6/EWWMSXMW+ERH7XS]I.4 Emv2, the only endogenous ecotropic murine leukemia virus of C57BL/6J mice. Retrovirology 9 306. =SYRK+64PSUYMR1.)OWQSRH9;EH[E17XS]I.4ERH/EWWMSXMW+ Negative selection by an endogenous retrovirus promotes a higheravidity CD4+ T cell response to retroviral infection. PLOS Pathogens 8I 307. =Y>&VERRMKER.%1SWW(/&V^S^S[WOM%1;MPOMRWSR%.,SPHIV%% 8EXI);ERH0IEXLIVFEVVS[6. Design and synthesis of inhibitors of Plasmodium falciparum N-myristoyltransferase, a promising target for anti-malarial drug discovery. Journal of Medicinal Chemistry 55¯ 308. >LES0>IZEPPSW7)6M^^SXM/.ISRK=0SZIPP&EHKI6ERH)TWXIMR(. Disruption of SoxB1-dependent Sonic hedgehog expression in the hypothalamus causes septo-optic dysplasia. Developmental Cell 22 298. ;MXLIVW1EVXMRI^'7YEVI^'*YPPI7/LIV74IR^S1)FINIV.4/SYWWMW /,EGOIXX*.MVKIRWSRW%*MRR4ERH&PEGOQER1. Plasmodium subtilisin-like protease 1 (SUB1): insights into the active-site WXVYGXYVIWTIGM½GMX]ERHJYRGXMSRSJETERQEPEVMEHVYKXEVKIX International Journal for Parasitology 42 299. ;SNXEW^0'PSYXMIV.1&EYQERR1(ERMIP/:EVKE.*Y.%REWXEWWMEHMW/ 7XI[EVX%*6IQqR]M%8YVRIV.1%ERH8zXL% Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms. Genes & Development 26 300. ;Y57SRK63VXSKIVS2>LIRK,)ZERSJJ67QEPP'0+VMW[SPH1( 2EQIOE[E7,6S]S,8YVRIV.1ERH=ER; The RNase III enzyme DROSHA is essential for microRNA production and spermatogenesis. Journal of Biological Chemistry 287 301. =ERK,84ETSYXWSTSYPSY7&IPMGL1&VIRHIV'.ER^IR.+ERXOI8 ,ERHPI]1ERH0I]7' Coordinate regulation of TPL-2 and NF-gB signaling in macrophages by NF-gB1 p105. Molecular and Cellular Biology 32 302. =EXE/0PS]H.1EWPIR7&PIY]EVH.=7OILIP17QIVHSR7.ERH)WEWLM* Plk1 and CK2 act in concert to regulate Rad51 during DNA double strand break repair. Molecular Cell 45 303. =SYRK(ERH:IVVIGO*%; Creativity in tuberculosis research and discovery. Tuberculosis 9277 MRC National Institute for Medical Research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¯VSYKLP]QSRXLP]QIIXMRKW 160 MRC National Institute for Medical Research MRC National Institute for Medical Research 161 6 Research themes index Biochemistry Dimitrios Anastasiou 0YM^4IHVSHI'EVZEPLS )ZE*VMGOIP .YWXMR1SPPS] John Offer Martin Webb Biophysics Tom Carter )H,YPQI .YWXMR1SPPS] 4IXIV6SWIRXLEP -ER8E]PSV Martin Webb 162 40 65 66 60 64 65 Cancer Dimitrios Anastasiou 7XIZI+EQFPMR Andres Ramos Steve Smerdon .IER4EYP:MRGIRX Martin Webb 68 98 Cell Biology Kate Bishop 1MOI&PEGOQER Tom Carter )ZE*VMGOIP 1E\+YXMIVVI^ 8SR],SPHIV 7XIZI0I] Tim Mohun .YWXMR1SPPS] )POI3FIV /EXVMR6MXXMRKIV Benedict Seddon Jim Smith 35 36 60 40 41 45 65 94 69 49 95 MRC National Institute for Medical Research Jonathan Stoye Peter Thorpe 51 96 Developmental biology .IER4EYP:MRGIRX (EZMH;MPOMRWSR 0]PI>MQQIVQER Andrew Oates 98 84 99 93 Evolutionary biology 4EYP(VMWGSPP 6MGLEVH+SPHWXIMR 1EPGSPQ0SKER 6SFMR0SZIPP&EHKI 61 63 90 91 Genetics and genomics 7MI[0ER%RK 4EYP&YVKS]RI 1MOI+MPGLVMWX *VERpSMW+YMPPIQSX 1EPGSPQ0SKER 6SFMR0SZIPP&EHKI Tim Mohun )POI3FIV -VMW7EPIGOIV Jim Smith Peter Thorpe James Turner :MGXSV8]FYPI[MG^ .IER4EYP:MRGIRX 6SFIVX;MPOMRWSR 1EVO;MPWSR 0]PI>MQQIVQER 89 80 90 91 94 83 95 96 53 98 55 56 99 Immunity John Doorbar )ZE*VMGOIP 38 40 1E\MQMPMERS+YXMIVVI^ +ISVKI/EWWMSXMW .IER0ERKLSVRI 7XIZI0I] Anne O’Garra :IRM^IPSW4ETE]ERRSTSYPSW Andres Ramos /EXVMR6MXXMRKIV Benedict Seddon +MXXE7XSGOMRKIV 4EZIP8SPEV :MGXSV8]FYPI[MG^ Andreas Wack 6SFIVX;MPOMRWSR 1EVO;MPWSR (SYKPEW=SYRK 41 43 44 45 48 68 69 49 50 53 54 55 56 Infectious disease Kate Bishop 1MOI&PEGOQER 0YM^4IHVSHI'EVZEPLS John Doorbar (IPQMVS*IVRERHI^6I]IW )ZE*VMGOIP 7XIZI+EQFPMR 6MGLEVH+SPHWXIMR 1E\MQMPMERS+YXMIVVI^ 8SR],SPHIV +ISVKI/EWWMSXMW .IER0ERKLSVRI .SLR1G'EYPI] Anne O’Garra 4IXIV6SWIRXLEP Steve Smerdon +MXXE7XSGOMRKIV Jonathan Stoye -ER8E]PSV 35 36 38 39 40 63 41 43 44 46 50 51 4EZIP8SPEV Andreas Wack 6SFIVX;MPOMRWSR 1EVO;MPWSR (SYKPEW=SYRK 54 55 56 Mathematical Biology 1MOI+MPGLVMWX 6MGLEVH+SPHWXIMR ;MPPMI8E]PSV 89 63 Neurosciences 7MI[0ER%RK James Briscoe Denis Burdakov %PI\+SYPH *VERpSMW+YMPPIQSX )H,YPQI 8VS]1EVKVMI :EWWMPMW4EGLRMW %RREPMWE4EWXSVI -VMW7EPIGOIV (EZMH;MPOMRWSR Physiology and Metabolism Dimitrios Anastasiou 7MI[0ER%RK Tom Carter 0YM^HI'EVZEPLS 4EYP(VMWGSPP 7XIZI+EQFPMR %PI\+SYPH 8VS]1EVKVMI Steve Smerdon +MXXE7XSGOMRKIV 1EVO;MPWSR 86 80 64 81 83 84 60 61 81 50 56 Stem cell biology %PI\+SYPH *VERpSMW+YMPPIQSX 6SFMR0SZIPP&EHKI :EWWMPMW4EGLRMW Peter Thorpe James Turner (EZMH;MPOMRWSR 80 91 96 84 Structural biology 1MOI&PEGOQER 4EYP(VMWGSPP 7XIZI+EQFPMR )H,YPQI %RREPMWE4EWXSVI Andres Ramos /EXVMR6MXXMRKIV Steve Smerdon Jonathan Stoye -ER8E]PSV ;MPPMI8E]PSV Martin Webb 36 61 64 68 69 51 Systems biology Dimitrios Anastasiou James Briscoe 0YM^HI'EVZEPLS +VIK)PKEV (IPQMVS*IVRERHI^6I]IW 1MOI+MPGLVMWX 1EPGSPQ0SKER %RREPMWE4EWXSVI (SYKPEW=SYRK 86 88 39 89 90 MRC National Institute for Medical Research 163 Index %REP]XMGEPYPXVEGIRXVMJYKEXMSR 108 %REWXEWMSY(MQMXVMSW %RK7MI[0ER Assistant Director 130 &MSPSKMGEPERH4VSGIHYVEP7IVZMGIW Bioresources 115 &MWLST/EXI 35 &PEGOQER1MOI &VMWGSI.EQIW &VSGO.SI &VS[R(SRRE &YVHEOSZ(IRMW &YXX.SERRE &YVKS]RI4EYP &Y\XSR6SKIV 'EVXIV8SQ 60 HI'EVZEPLS0YM^4IHVS 'LYRK6EGLIP 'SQTYXMRKERH8IPIGSQQYRMGEXMSRW 'SPPMRW/EX 'SRJSGEPMQEKMRKERHEREP]WMW 109 (EZ]'PEVI Director of Operations 130 Director of Research 130 Director of Studies (SSVFEV.SLR (VMWGSPP4EYP )PIGXVSRGV]SQMGVSWGST] 114 )PIGXVSR1MGVSWGST] 111 )PIGXVSRMGMRWXVYQIRXTVSXSX]TMRKERHWYTTSVX )PKEV+VIK *EGMPMXMIWERH-RJVEWXVYGXYVI7IVZMGIW *IVRERHI^6I]IW(IPQMVS 39 *PS[G]XSQIXV] 118 *VIROMIP8SQ *VMGOIP)ZE 40 +EVGI^4EXVMGME +EQFPMR7XIZI +IRIVEPWIVZMGIW Genomics 116 +MFWSR%RRE +SPPERH&IR 19 +MPGLVMWX1MOI +SPHWXIMR6MGLEVH +SYPH%PI\ +Y=ER 109 +YMPPIQSX*VERGSMW +YXMIVVI^1E\ ,EVX[IKIV,EVEPH ,MKLXLVSYKLTYXWIUYIRGMRK 116 ,MVWX0M^ 111 ,MWXSPSK] 110 ,SPHIV8SR] ,S[IPP7XIZI 106 ,YPQI)H Insectary -SR(EZMH .SLRWSR7EVEL 103 /EWWMSXMW+ISVKI 0ERKLSVRI.IER 0EVKIWGEPIPEFSVEXSV] 115 0EVVSY]1EYQYW+IVEPH 0IZIPLMKLGSRXEMRQIRXZMVYWPEFSVEXSV] 119 0I]7XIZI 0MFVEV]MRJSVQEXMSR GSQQYRMGEXMSRW 0MRK%PER 0SKER1EPGSPQ 0SZIPP&EHKI6SFMR 0YRR]'PMZI 1ELQSSH6EHQE 110 1EVKVMI8VS] 164 MRC National Institute for Medical Research 130 1EVVSR1MGLIPI 106 Mass Spectrometry 1EXLIVW/EXLPIIR 1G'EYPI].SLR 1G+YMVI'LVMWXMRE 1IGLERMGEP)RKMRIIVMRK 115 Media Production Microarray 19 1MXGLIPP%PMGI 1SLYR8MQ 1SPPS].YWXMR 16'&MSQIHMGEP216'IRXVI 2SVQER*VERO 3´+EVVE%RRI 93 3EXIW%RHVI[ 94 3FIV)POI 3GGYTEXMSREP,IEPXL 3GLW1IPZMR 66 3JJIV.SLR 348ERH,6)1MQEKMRK 4EGLRMW:EWWMPMW 18 4EPQIV0YG] 48 4ETE]ERRSTSYPSW:IRM^IPSW 4EWXSVI%RREPMWE 115 4E]RI.SEGLMQ 4LSXSKVETLMGW 118 4VIIGI+VELEQ 103 4VSGIHYVEP7IVZMGI7IGXMSR 4VSXIMRWIUYIRGIEREP]WMWERHWXVYGXYVIQSHIPMRK 6EQSW%RHVIW 6MXXMRKIV/EXVMR 6SWIRXLEP4IXIV 7EJIX] 7IGYVMX] 7EPHERLE.SWq 83 7EPIGOIV-VMW 7GMIRXM½G)UYMTQIRX'EVI 7IHHSR&IRIHMGX 7IWE]%FHYP 113 7MRKPIQSPIGYPIXIGLRMUYIW 7QIVHSR7XIZI 7QMXL.MQ 106 7RMNHIVW&VEQ 7XEGL0EWWI 7XSGOMRKIV+MXXE 7XSTTW1EVX]R 7XS]I.SREXLER 8E]PSV;MPPMI 8E]PSV-ER 8LSVTI4IXIV 8SPEV4EZIP 8YRK7MQ 8YQ[MRI-VIRI 8]FYPI[MG^:MGXSV 8YVRIV.EQIW 18 :MPPE1EXXIS :MRGIRX.IER4EYP 54 ;EGO%RHVIEW Web Team ;IFF1EVXMR ;,3'SPPEFSVEXMRK'IRXVIJSV6IJIVIRGIERH6IWIEVGL 58 SR-R¾YIR^E;-' ;MPOMRWSR6SFIVX ;MPOMRWSR(EZMH ;MPPW+EFVMIP 130 ;MPPW.SLR ;MPWSR1EVO 105 <VE]GV]WXEPPSKVETL] =SYRK(SYKPEW >MQQIVQER0]PI 16'2EXMSREP-RWXMXYXIJSV1IHMGEP6IWIEVGL 8LI6MHKI[E] 1MPP,MPP 0SRHSR2;%% 8IP *E\ MRC NIMR location map %2SVXL XS1,IEXLVS[ERH7XERWXIH%MVTSVXW 1 E 1EVWL 0 RI SH , M P P % HUL 1 & M X X E % G] MPP , IX&]TEWW 1MPP,MPP)EWX 1 . , EPI 0ER (SPPMW6 SEH % ,IRHSR EH ; EXJS TLYZ 3 /HT L 3H U I +H^Z 8LI6 MHKI[ &EVR 1MPP,MPP &VSEH[E] E] % 1MPP,MPP&VSEH[E]8LEQIW0MRO XS'IRXVEP0SRHSRZME/MRK´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