CIR Annual Report for 2009

Transcription

2009
Annual Report
Centre for
Immune Regulation (CIR)
Ce
ion
IR
n tr
e fo
lat
u
g
r Immune Re
Vision statement
This centre identifies and
investigates novel mechanisms of
immune dysregulation to advance
the development of therapeutics
Key accomplishments 2009
• Establishment of a new method whereby development of autoimmune disease
due to immune dysregulation can be visualized kinetically in intact mice.
• Identification of a key aspect of the HLA (MHC) association with coeliac disease.
The finding helps to understand why the disease develops in certain individuals.
• Development of novel methods in phage display technology. The purpose is to
improve stability and expression levels of soluble T-cell receptors and peptide
MHC complexes. This will assist us in the characterisation of adaptive immune
responses.
• Showing that the positive effect sun bathing has of psoriasis lesions is mediated
through its effect on the immune system.
• Characterisation of a new molecule in the transport pathway from the Golgi
complex to the endosomal pathway.
Duodenal villi (wholemount preparation). HLA-DR-staining (photo: Ann-Christin R. Beitnes).
2
Director´s comments
Ludvig M. Sollid
Centre Director
In 2009 the Centre for Immune Regulation has been
running at full steam. There have been many activities.
Perhaps the most exciting events have been the visits
from our Visiting Professors. We had visits from Richard
Blumberg (Harvard Medical School) in February,
Jacques Neefjes (Netherlands Cancer Institute) in March,
Mark Shlomchik (Yale University) in May and Kai
Wucherpfennig (Harvard Medical School) in September.
They all spent a full week at the centre; giving lectures
and seminars and interacting closely with the students
and the postdocs. My impression was that all our Visiting
Professors enjoyed their stays. They felt that the week at
CIR was demanding and intense, but rewarding. What
I can say for sure is that all the members of CIR were
very happy with these visits. “Highly inspiring” and “most
useful” were words I heard. Thus, on behalf of CIR I
would like to extend my thanks wholeheartedly to our
Visiting Professors for them taking time out of their busy
schedules and for leaving behind so much of their insight
and knowledge.
It is our ambition that our centre should not only
benefit the members of CIR, but also be of value for
scholars outside the centre. Admission to the lectures
by the Visting Professors and other invited speakers has
been open to everyone. In conjunction with the visit of
Richard Blumberg we arranged a mini-symposium on
Inflammatory Bowel Disease and in conjunction with
the visit of Mark Shlomchik we arranged a workshop on
Autoimmunity and Autoimmune Diseases. At both these
events many of the speakers were non-members of CIR.
The outside speakers responded positively to invitations
to lecture, and the turnout at both these events was very
good. This is very inspiring for us in CIR knowing that our
efforts to reach out are appreciated.
There were 3 dispuations at CIR in 2009; Anders
Sandvik, Lars-Egil Fallang and Michael Zangani – they
all completed their PhDs during the year. I thank the
opponents for their effort in evaluating the work of our
candidates and for making the disputations memorable
events.
We have a postdoc committee at CIR who is hosting a
seminar series. There were two speakers in this series in
2009; Hidde Ploegh gave a lecture in March and Jeffrey
V. Ravetch gave a lecture in May. I am hoping to see
additional top international scientists holding lectures for
CIR as well as the immunological community of Oslo in
2010.
CIR’s gender equality programme became operative in
2009 and has focused on two areas; one is a mentoring
programme for female postdocs and the other is that
CIR has allocated funding to pay for technical assistance
for female postdocs with young children. A total of 10
postdocs entered the mentoring programme and they
were assigned individual mentors from outside CIR, and
four female postdocs were provided with three months
technical help each from master students who were
temporarily employed for this task. The CIR management
and the group leaders hope these efforts will help our
talented female researchers to become independent
scientists.
I take this opportunity to thank Elin Lunde for her hard
work and strong effort as CIR’s administrative leader.
This position was taken over by Stine Bergholtz at the
beginning of 2010. In the interim between Elin’s departure
and Stine’s arrival, Anders Sandvik gave an efficient
helping hand to CIR which was extremely valuable. On
behalf of CIR, I am extending a warm thank to Anders.
I also welcome Stine and very much look forward to
working with her.
On writing these words, 2010 has commenced. Inger
Sandlie’s group has just relocated its activities from the
Institute of Molecular Biosciences at Blindern to the
Institute of Immunology at Rikshospitalet. This colocalisation of activities is something we have very much
been looking forward to, and I am sure this will strengthen
the research of CIR. I feel confident that CIR will become
even stronger in 2010.
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Duodenal villi (wholemount preparation). Laminin-staining (photo: Ann-Christin R. Beitnes).
4
Index
Vision statement
2
Key accomplishments 2009
2
Director´s comments
3
Scientific currency
6
Patents and industrialisation
7
Core competency
8
Inger Sandlie’s group
10
Ludvig Sollid’s group
12
Bjarne Bogen’s group
14
Finn-Eirik Johansen’s group
16
Oddmund Bakke’s group
18
Guest professor program
20
Minisymposium and Workshop
22
Guest lectures
23
Guest researchers
23
Internal activities
24
Education and career progression
25
Gender equality program
25
Management and boards
26
Appendices
27
Appendix 1) CIR staff and students
27
Appendix 2) Publications
32
Appendix 3) Presentations given outside CIR
35
Appendix 4) Press coverage
40
Appendix 5) Collaboration
41
Appendix 6) Funding
43
5
Scientific currency
Papers
During 2009 CIR published 34 papers, and has already by
the end of February 2010 14 papers published or in press.
Of the papers published in 2009, seven have an impact
factor above 6.0 and two of these have an impact above
20.0. Also of the papers published in 2009, 13 are a result
of international collaboration, 9 of collaboration within
Norway and 2 with both international and national
collaboration. A complete publication list is given in
appendix 2.
Books and book chapters
In 2009 CIR members contributed to nine books or book
chapters. A complete list of books and book chapters is
given in appendix 2.
Patents
Research from the centre resulted in filing of five patent
applications in 2009.
Talks and posters
Impact factor of papers
CIR members gave 64 oral presentations at conferences
or meetings outside their respective institutions, and 43 of
the speakers were invited by the organisation committee.
Also 26 posters were presented at international confer
ences. Complete lists of talks and posters are given in
appendix 3.
79%
Media coverage
5%
16%
Impact 6 - 20
Impact <6
Research from the centre was presented once on TV and
once on radio. Also research from the centre appeared
five times in public papers, three times in internal papers
at the University of Oslo or Oslo University Hospital
Rikshospitalet and twice in popular science magazines.
A complete lists of media coverage is given in appendix 4.
Impact >20
Prizes and awards
Papers with collaboration (34 papers total)
2
13
9
Contribution to local research environment
10
International
National
International and national
6
Michael M. Zangani received the Norwegian Society for
Immunology (NSI) research award price 2009. The award
is given to the first author of an outstanding original
scientific paper in the field of immunology. Zangani was
awarded the prize for the paper Lymphomas can develop
from B cells chronically helped by idiotype-specific T cells
(J. Exp Med. 2007 May 14; 204 (5): 1181-1191) by authors
Michael M. Zangani, Marianne Frøyland, Gao Yue Qin,
Leonardo A. Meza-Zepeda, Jeffrey L. Kutok, Keith
M. Thompson, Ludvig A. Munthe and Bjarne Bogen.
The prize was announced and presented at the Day of
Immunology, April 24th 2009.
CIR only
CIR aims at contributing to the immunological research
environment in Oslo by contributing financially and
scientifically to the Norwegian Society for Immunology
(NSI). In addition, guest lecturers, mini symposia and
work shops arranged by CIR are open to anyone that is
interested.
Patents and industrialisation
Vaccibody
Two of the groups (Bogen and Sandlie) have developed
novel vaccine molecules that in animal experiments
induce superior immune responses in a variety of test
systems. The vaccine molecule (vaccibody) has been
designed by use of molecular biology techniques. The
molecule has the ability to target antigen presenting
cells for efficient delivery of antigen and elicitation of
enhanced immune responses. The vaccine is delivered
as DNA plasmids to muscle or skin, in conjunction with
electroporation that enhances uptake into cells. Such
transfected cells produce and secrete vaccibody proteins
that target antigen presenting cells and load them with
antigen for presentation to lymphocytes. Ongoing studies
focus on application of vaccibodies to cancer (B cell
lymphomas, prostate cancer) and infections (influenza,
HIV, tuberculosis). A patent application (inventors Bjarne
Bogen, Inger Sandlie and Agnete Brunsvik Fredriksen)
has been filed, and a company, Vaccibody AS, has been
formed where Bjarne Bogen and Inger Sandlie serve
on the scientific panel. Part of the research activities of
the company, funded in part by the Research Council of
Norway, takes part in Bjarne Bogen’s lab according to a
contract between Oslo University Hospital Rikshospitalet
and Vaccibody AS.
Extending in vivo half-life of small drugs
The efficacy of chemical drugs, peptides, small proteins
and engineered antibody fragments are hampered by
short serum half-life, ranging from minutes to a few hours.
Therefore, strategies to tailor their serum persistence
and biodistribution are needed. Inger Sandlie and Jan
Terje Andersen have developed a unique technology
that may solve the problem. Their discovery may extend
in vivo half-life of potentially all small drugs. This will
ultimately result in enhanced treatment efficiency,
more favourable dosing regimes and improved patient
compliance. Together with the technology transfer office
at the University of Oslo, Birkeland Innovation, they
have signed an agreement with the world leading bio
innovation company Novozymes Biopharma. So far, two
patents have been filed.
Stopping autoimmunity before it strikes
Autoimmune diseases such as lupus, multiple sclerosis,
rheumatoid arthritis and diabetes are caused when the
immune system attacks the body’s own cells. Normally,
immune cells are prevented from attacking normal cells;
however, in patients with autoimmune disease, this
“tolerance” is lost. The immediate causes of autoimmune
diseases remain unknown, partially due to the inability
to detect disease before the onset of symptoms. Early
detection of autoimmune disease is critical for assessing
new treatments. The molecule NF-κB is activated by
inflammation, which plays a key role in autoimmune
disease development, making NF-κB a prime candidate to
track autoimmune activity. Researchers at the University
of Oslo led by Ludvig Munthe and Bjarne Bogen in
collaboration with Rune Blomhoff engineered NF-κB
such that it would emit light when activated. Using a
mouse model of systemic autoimmunity with features
of lupus, they found that NF-κB activation signals were
present in affected organs several weeks before the
clinical manifestations of disease. The light signal intensity
correlated with disease progression. NF-κB tracking may
therefore provide a new tool in the evaluation of early
autoimmune therapies.
Signal sequence independent phage display
Phage display is the dominating technology in basic and
applied protein discovery and for development of novel
protein based diagnostics and therapeutics. Nextera AS,
a new biotechnology company founded in 2009, offers
a new phage display platform named signal sequence
independent phage display - SSIp display, invented by
post doc Geir Åge Løset during his work in Inger Sandlie’s
lab. SSIp display is more efficient than conventional
methods. Furthermore we have introduced a tag into the
virion body. The last factor is essential for automation of
phage display and high throughput screening. Nextera
was founded in august 2009 by Bio-Medisinsk Innovasjon
AS, Birkeland Innovasjon AS, Geir Åge Løset and Inger
Sandlie. Nexteras technology is protected by four separate,
patents, one granted and three pending.
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Core competency
Core competency at CIR
• A wide variety of cellular and humoral immune assays.
• Advanced methods in molecular biology, proteomics and cellular imaging.
• Disease models in humans and in animals. The models are used to understand the
molecular mechanisms of immune regulation and autoimmunity.
• Transgenic mouse models.
• Functional characterisation of immune cells in human tissue.
• Study of immune molecules and their intracellular functions in antigen presenting cells.
• Molecular engineering for the development of new therapeutic agents and research
reagents.
IL-2
T cell
IL-1
IL-17
IL-4
IL-6
INFg
soluble TCR
Antigens
Vaccibody
CH3
FcRn-IgG
CH3
gluten
Bogen group
Sollid group
Sandlie group
Johansen group
Endosome
Bakke group
Epithelial
cell
Nucleus
Antigen presenting cell
MIIC
ER
Lamina propria
Illustration of research focus of the five groups in CIR (Bogen group, Sollid group, Bakke group, Sandlie group
and Johansen group). (Illustration: Tone Gregers).
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• Cellular immunology
• Experimental studies in mice
• Transgenic mice
• Recombinant Ig vaccine design
Finn-Eirik Johansens group
• Human model of airway allergy in vitro
and in vivo
• Mucosal antibody system
• Dendritic cells
• Immunohistochemistry
• Flow cytometry
• Human cellular immunology
• In vitro study of CD4+ T cells
• Recombinant soluble HLA molecules
• Mass Spectrometry and proteomics
• Characterisation of lymphocyte
antigen receptors
• Live cell Imaging
• Confocal microscopy
• Characterisation of intracellular
trafficking pathways
• Transfection of cells and the study of
binding kinetics of cytosolic molecules
• Structure and ligand binding
properties of antibodies and T-cell
receptors
• Phage display
• Recombinant molecule expression and
purification
• Interaction studies
CIR is associated to the University of Oslo, which is the host organization, and the Oslo University Hospital Rikshospitalet.
The centre consists of five groups with different scientific expertise. Inger Sandlie’s and Oddmund Bakke’s groups are affiliated
the Department of Molecular Bioscienses (IMBV) at the Faculty of Mathematics and Natural Sciences. Bjarne Bogen’s and
Ludvig Sollid’s groups are affiliated Department of Immunology (IMMI) and Finn-Erik Johansen Department Laboratory for
Immunohistochemistry and Immunopathology, Institute of Pathology (LIIPAT) at the Medical Faculty.
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Achievements in 2009
• Found that mouse albumin binds much more strongly to the human receptor
that regulates serum half life than human albumin does. This is important for the
understanding of half life regulation of serum molecules and design of therapeutics
(J Biol Chem 2009).
• Developed a novel phage display technology platform that improves performance as
compared to the current state of the art (patents pending and manuscript submitted).
Ambitions for 2010
• Understand the interaction between the half life regulating receptor and it’s ligands at
the amino acid level and test the biodistribution of mutant ligands in animal models.
• Design improved molecular trackers for specific antigen presentation.
• Dissect the molecular interaction of gluten reactive T-cell receptors with gluten peptide
– HLA-DQ2 complexes.
Model of a T-cell receptor that has been engineered for improved stability using phage
display. Five amino acid substitutions were identified that increase stability, and these are
highlighted.
Overview of research in the group
The Sandlie group studies the structure and function of
antibodies and T-cell receptors, the specific detecting
molecules of the adaptive immune system. The purpose
of the work is to engineer soluble T-cell receptors,
antibodies and antibody derived molecules to be used in
therapy and as research reagents.
We focus on two projects: A) Studies of the interaction
between Fc receptors, and in particular the neonatal Fc
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receptor, with IgG subclasses and albumin. Key questions
are how ligand binding elicits antibody effector functions of
IgG subclasses and regulate serum half life. B) Expression
of soluble T-cell receptors for the detection complexes
between antigenic peptides and Major Histocompatibility
Complex (MHC, in humans HLA) molecules.. The focus
is on engineering of T-cell receptors to increase stability
and affinity for ligands that are characteristic of disease
models studied in other groups at CIR.
Key project summaries
Proteins in the blood stream are short lived and normally
degraded within a few hours or days, but the two most
abundant proteins, IgG and albumin, are rescued from
degradation and have half-lives of three weeks. The
rescue mechanism depends on their interaction with
the neonatal Fc receptor, FcRn. For us, it is crucial to
understand how FcRn rescues IgG and albumin, and to
study whether long half life may be transferred to other
protein therapeutics. Therapeutics and diagnostics are
often fused to human albumin and tested in mice and
rats. Therefore, it is important to understand how human
albumin binds to mouse FcRn. In 2009, we reported a
biochemical analysis of how mouse and human FcRn bind
to human and mouse albumin. Surprisingly, we found
a hundred fold difference in binding affinity between
binding pairs. Specifically, mouse receptor bound human
albumin very weakly, while the human receptor bound
strongly to mouse albumin. We compared the human and
mouse receptors and were able to identify the amino acids
that cause the difference. This explains why therapeutics
that are conjugated to human albumin and tested in mice
show a poor increase in half life.
To ask questions regarding the nature of the antigen
presenting cell, the location and kinetics of peptideMHC assembly and the interaction of specific peptideMHC molecules with T cells at the atomic level, specific
detection molecules are needed. Soluble T-cell receptors
are new tools for such studies in health and disease.
Furthermore, they may block the binding of specific
peptide-MHC, be used as diagnostics or as immunotoxins.
Phage display has been instrumental for the success of
antibody technology. We have explored phage display
of soluble T-cell receptors and established a platform
that supports engineering and selection of specific T-cell
receptors with improved stability and affinity. To this
end we have developed a novel phage display platform
called Signal Sequence Independent phage display – SSIp
display. The finding is that two viral capsid proteins, pVII
and pIX, display fusion proteins extremely well. The
technology (manuscript submitted) is protected by a total
of 4 pending patents and is the core technology of a new
biotechnology company founded in 2009 – Nextera AS
(www.nextera.no).
Central publications and patents in 2009
Jung ST, Reddy ST, Kang TH, Borrok MJ, Sandlie I, Tucker
PW, Georgiou G (2010) “Aglycosylated IgG variants
expressed in bacteria that selectively bind FcgammaRI
potentiate tumor cell killing by monocyte-dendritic cells”
Proc Natl Acad Sci U S A, 107 (2), 604-9
Andersen JT, Daba MB, Berntzen G, Michaelsen TE,
Sandlie I (2010) ”Cross-species binding analyses of
mouse and human neonatal Fc receptor show dramatic
differences in immunoglobulin G and albumin binding” J
Biol Chem, 285 (7), 4826-36
Andersen JT, Daba MB, Sandlie I (2010) ”FcRn binding
properties of an abnormal truncated analbuminemic
albumin variant” Clin Biochem, 43 (4-5), 367-72
Michaelsen TE, Sandlie I, Bratlie DB, Sandin RH, Ihle
O (2009) ”Structural difference in the complement
activation site of human IgG1 and IgG3” Scand J
Immunol, 70 (6), 553-64
pVII Phage Display
PCT international publication
Geir Åge Løset (filed by Bio-Medisinsk Innovasjon AS)
Signal Sequence-Independent pXI Phage Display
US provisional application
Geir Åge Løset (filed by Bio-Medisinsk Innovasjon AS)
Multivalent Phage Display Systems and Methods
Geir Åge Løset and Inger Sandlie (filed by Bio-Medisinsk
Innovasjon AS)
Phage vs Phage Library Panning
Herald Reiersen, Geir Åge Løset and Urs Hagemann
(filed by Affitech Research AS)
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• Identified a novel mechanism that explains why the MHC class II molecule HLADQ2.5 is a risk factor for several autoimmune diseases (Nat Imm 2009).
• A quantitative analysis of transglutaminase 2 (TG2) mediated deamidation of gluten
peptides, an enzyme-mediated modification of gluten antigen from wheat, demonstrated
that the enzyme’s preference shapes the T-cell response in coeliac disease (J Proteome
Res 2009).
• Helped clinical gastroenterologists in the diagnosis of difficult uncertain cases of
coeliac disease by using newly established experimental techniques (gluten challenge
and tetramer staining).
Ambitions for 2010
• Establish model system for the study of molecular mechanisms for gluten-dependent
production of anti-TG2 antibodies in coeliac disease patients.
• Dissect the molecular interaction of gluten reactive T-cell receptors with gluten peptide
– HLA-DQ2 complexes.
Hydrogen-bonding network surrounding the polymorphic tyrosine residue at position a22 in HLADQ2.5. The HLA-2.2 molecule is carrying a phenylalanine at this position and can not establish this
hydrogen-bonding network. From Fallang et al, Nat Imm 2009.
12
Our group is trying to dissect the interplay environ
mental factors and genetic factors in chronic autoimmune
disorders, such as coeliac disease, type 1 diabetes,
rheumatoid arthritis and multiple sclerosis. People
with coeliac disease get sick when they eat bread or
other gluten containing food. We are concentrating on
coeliac disease as a model to understand the molecular
mechanisms leading to chronic inflammatory disease.
In particular, we focus on how certain variants of HLA
(MHC) molecules predispose to disease development.
Over the years, we have generated a large panel of CD4+
T-cells lines and clones cultured from intestinal biopsy
specimens from coeliac disease patients. Characterisation
of what and how these T cells recognise gluten protein,
the dietary antigen precipitating coeliac disease, has lead
to many interesting findings such as the importance of
protein structure on antigen processing, how enzyme
mediated
post-translational
protein
modification
increases antigenicity and how HLA binding specificity
and peptide-MHC stability influence T-cell priming.
This knowledge does not only impact the understanding
of coeliac disease pathogenesis, but also reveal general
principles of immune regulation that are applicable to
other disease models.
Coeliac disease patients show strong association with
particular alleles within the HLA complex (HLA)
complex. Carriers of HLA-DQ2 have 30-fold higher risk of
developing coeliac disease. HLA-DQ2 is directly involved
in the pathogenesis of coeliac disease by binding and
presenting gluten peptides, fragments of wheat protein, to
disease-specific T cells in coeliac patient intestines. Using
mutagenesis of soluble recombinant HLA molecules and
peptide binding studies, we identified a previously little
appreciated aspect of peptide binding to MHC class II
molecules. There are two variants of HLA-DQ2; HLADQ2.5 and HLA-DQ2.2 and these molecules are highly
similar but they display disparate disease associations. We
found that one key polymorphic residue on the HLA-αchain (α22) determines the presence (DQ2.5) or absence
(DQ2.2) of a hydrogen bond to the peptide backbone,
which in turn affects the kinetic stability of peptides
bound to DQ2. The better ability of DQ2.5 to keep its
peptide cargo will increase the opportunity for T-cell
activation in vivo, thus increase the likelihood of disease
development.
The presence of circulating IgA and IgG antibodies
targeting the auto-antigen tissue transglutaminase (TG2)
is a specific feature for active coeliac disease. TG2 is an
enzyme that catalyses either transamidation resulting in
cross-linking of two peptides, or deamidation of glutamine
residues to glutamate. Deamidation introduces negative
charges in the target protein, which in the case of gluten,
increases its binding to HLA-DQ2. Mass spectrometric
methods were developed to quantify TG2-mediated
deamidation of gluten epitopes and a correlation between
their deamidation rate and frequency in patients was
found. These results further demonstrate that the enzyme
kinetics of TG2 can fine-tune the pathogenic glutenreactive T-cell responses in coeliac disease. Currently our
group is trying to understand how disease specific autoantibodies to TG2 are generated, and why auto-antibody
production is dependent on HLA-DQ2 expression and as
well as gluten exposure.
Central publications in 2009
Fallang LE, Bergseng E, Hotta K, Berg-Larsen A, Kim CY,
Sollid LM (2009) ”Differences in the risk of celiac disease
associated with HLA-DQ2.5 or HLA-DQ2.2 are related
to sustained gluten antigen presentation” Nat Immunol,
10 (10), 1096-101
Dørum S, Qiao SW, Sollid LM, Fleckenstein B (2009) “
A quantitative analysis of transglutaminase 2-mediated
deamidation of gluten peptides: implications for the T-cell
response in celiac disease” J Proteome Res, 8 (4), 1748-55
Olsen I, Tollefsen S, Aagaard C, Reitan LJ, Bannantine
JP, Andersen P, Sollid LM, Lundin KE (2009) “Isolation
of Mycobacterium avium subspecies paratuberculosis
reactive CD4 T cells from intestinal biopsies of Crohn’s
disease patients” PLoS One, 4 (5), e5641
Jabri B, Sollid LM (2009) “Tissue-mediated control of
immunopathology in coeliac disease” Nat Rev Immunol,
9 (12), 858-70. Review
13
• Established a new method whereby development of autoimmune disease du to immune
dysregulation can be visualized kinetically in intact mice ( Am. J. Pathol 2009).
• Demonstrated that secretion of tumour specific antigen is of crucial importance for
tumour rejection by a subtype (CD4+) of T cells (Cancer Research 2009).
• Developed hemagglutinin-based vaccibody DNA vaccines for influenza that confer
protection to virus challenge (unpublished).
Ambitions for 2010
• To describe novel mechanisms for receptor-mediated interactions between lymphocytes
that may cause autoimmune disease and tumour development.
• To further develop and translate into the clinic novel vaccine molecules for cancer and
infectious diseases.
Gradual development of autoimmune inflammation in mice by activating a firefly protein (luciferace)
with a transcription factor (NF-κB) in inflamed tissue (Photo: Ludvig Munthe).
14
The Bogen group runs projects with three areas, 1)
Idiotype-driven T-B collaboration and its role in health
and disease, 2) Novel vaccine molecules for cancer and
infectious diseases, 3) The mechanism by which CD+ T
cells can reject cancer cells. These three research topics,
for which key summaries are given below, may at first
glance seem separate but are in fact closely related. The
common theme is immunoglobulins and how these may
be recognised by T cells. Further, parts of immunoglobulins
are used as modules for the group’s development of novel
vaccine molecules.
Idiotype-driven T-B collaboration and its pathogenic
role in elicitation of autoimmune disease and cancer.
Bjarne Bogen and co-workers has over the last 25 years
painstakingly established a novel type of interaction
between T and B lymphocytes where T-cells recognise Ig
variable region-derived idiotypic (Id) peptides presented
on the MHC II molecules on the surface of B cells. When
the B cell receive help from such Id-specific T cells,
and the B-cell at the same time recognize a self antigen
with it’s B-cell receptor for antigen, the B cell, receiving
these two separate signals, will be activated, proliferate
and differentiate. Our previous work has shown that
this mechanism may cause immune dysregulation,
autoimmunity and B lymphoma development in mice. In
2009 we have started efforts to extend this pathogenic
mechanism to patients with Chronic Lymphatic
Leukaemia (CLL) and systemic Lupus Erythematosus
(SLE). These efforts will continue in 2010. At the same
time we are extending our studies of the basic mechanisms
by establishing new strains of transgenic and knock-in
mice.
8
Vaccine development. Key accomplishments in 2009 have
been to extend application of Vaccibody molecules to
influenza, HIV and tuberculosis. In 2010 we will continue
these studies and also try to develop more potent versions
of the molecules. We will also try to develop vaccine
molecules for human application.
Tumour immunology. Main accomplishment in 2009
was the demonstration that secretion of tumour specific
antigen is mandatory for elicitation of tumour protective
T-cell responses. In 2010 we will in further detail study
the mechanisms of rejection.
Central publications and patents in 2009
Zangani M, Carlsen H, Kielland A, Os A, Hauglin H,
Blomhoff R, Munthe LA, Bogen B (2009) “Tracking early
autoimmune disease by bioluminescent imaging of NF-κB
activation reveals pathology in multiple organ systems”
Am J Pathol, 174 (4), 1358-67
Corthay A, Lundin KU, Lorvik KB, Hofgaard PO, Bogen
B (2009) “Secretion of tumor-specific antigen by myeloma
cells is required for cancer immunosurveillance by CD4+
T cells” Cancer Res, 69 (14), 5901-7
Holmøy T, Vartdal F, Hestvik AL, Munthe L, Bogen B
(2010) ”The idiotype connection: linking infection and
multiple sclerosis” Trends Immunol, 31 (2), 56-62
Patent application (US): Triple transgenic mouse model of
autoimmune disease and NF-kB in vivo imaging. Ludvig
Munthe, Harald Carlsen, Rune Blomhoff, Bjarne Bogen.
Filed by Birkeland/UiO.
15
Finn-Eirik Johansen’s group
• Showed that the positive effect sun bathing has of psoriasis lesions is mediated through
its effect on the immune system.
• Identified a novel pro-allergic pathway in which altered lipid composition in the
epidermis drives allergic inflammation.
• Revealed redundant mechanisms of immune defense against commensal intestinal
microbes.
Ambitions for 2010
• Increase our understanding of how pollen allergens trigger the allergic reaction in
airway allergy.
• Determine effects commensal microbiota have on host immune system.
HLA-DR+ antigen presenting cells (brown colour) within and beneath the surface epithelium in
human bronchial mucosa. Note cellular extensions between the epithelial cells enabling direct antigen
sampling on the luminal side (photo: Frode Jahnsen).
16
We work in mucosal immunology, with a particular
emphasis on how innate and adaptive immune systems
communicate and cooperate. Our projects follow
two main lines: mechanisms of allergy development
and mechanisms of peaceful coexistence between the
enormous amount of intestinal bacteria and the host.
Failure of peaceful coexistence may lead to chronic
inflammatory conditions in the intestinal system, but
dysbiosis between intestinal bacteria and the host is
also involved in other human conditions such as allergy,
diabetes and obesity. In these systems we use a variety of
human and animal models including allergen provocation
studies in patients.
Mechanistic understanding of early events in the allergic
reaction is important to identify new targets for therapy
to allergic disorders. We have therefore established ex
vivo model of human pollen allergy in which mucosal
biopsy specimens obtained out of season are challenged
with pollen extracts or recombinant peptides for a short
period. Our results strongly suggest that in biopsies from
allergic patients mucosal-residing T cells interacting with
antigen presenting cells produce significant amounts of
IL-5 in response to allergen challenge. We propose that
memory allergen-reactive T cells may be a driving force
in the inflammation in allergic rhinitis.
The human gut harbours a microbiological community
of 100 trillion bacteria consisting of more than a 1000
species. Appropriate cross talk between the host and its
intestinal microbiota is of obvious significance for the
function of the intestines, and has also been shown to be
important for several immune-mediated diseases such as
in allergy and asthma. Thus, intestinal microbes provide
benefits to the host, but can become pathogenic if allowed
to breach the epithelial barrier of the gut. Secretory
antibodies are the main adaptive effector component
reinforcing the epithelial barrier and we have shown that
in the absence of this antibody system, innate defence
functions of the epithelium are activated. Thus, there
is a redundancy between adaptive immunity (secretory
antibodies) and innate immunity (defensins etc.) to
reinforce the epithelial barrier in the gut.
8
In a prospective study we examined the effect of sun
therapy on the immune system in psoriatic patients that
were treated with natural sun exposure on the Canary
islands for 16 days. We showed that sun therapy had
excellent clinical effect in psoriatic skin and resulted
in dramatic and rapid reduction in numbers of both
plasmacytoid and myeloid dendritic cells as well as both
CD4+ and CD8+ T cells. This reduction in cell numbers
occurred concomitantly with reduced expression of
inflammatory cytokines (e.g. type I IFN, IL-17 and IL23). The effects on immune cells and cytokine expression
preceded clinical improvement suggesting that these
events are important for the health benefits of sun bathing
in psoriasis.
Mutations in the SLC27A4 gene encoding the fatty acid
transporter protein 4 cause a mild form of congenital
ichthyosis designated ichthyosis premature syndrome.
We have shown that this subtype of ihthyosis is
characterized by blood eosinophilia, high serum IgE and
allergic manifestations in several organs including atopic
dermatitis-like lesions. We furthermore demonstrate
that the Th2-like inflammatory skin reaction is already
established at the fetal stage strongly suggesting that
the proallergic process in IPS is independent of barrier
function and external stimuli. Our results demonstrate
that disturbed lipid metabolism in the skin trigger a
local innate allergic inflammation which paves the
way for sensitization to a variety of allergens. We have
thus identified a novel pro-allergic pathway in which
altered lipid composition in the epidermis drive allergic
inflammation. Further studies will focus on how altered
composition of lipid in the skin affects immune functions.
Karlsson MR, Johansen FE, Kahu H, Macpherson A,
Brandtzaeg P (2009 Nov 3. [Epub ahead of print])
“Hypersensitivity and oral tolerance in the absence of a
secretory immune system” Allergy (in press)
Holt PG, Strickland DH, Bosco A, Jahnsen FL (2009)
“Pathogenic mechanisms of allergic inflammation: Atopic
asthma as a paradigm” Adv.Immunol., 104, 51-113
17
• Identified function of a new Rab (Rab7b) and its trafficking pattern in model cells
(Progida et al., JCS, in press).
• Characterisation of fusion and fission in invariant chain stimulated model cells.
• Characterised coupling between MHC class II and invariant chain in dendritic cells
from cancer patients and healthy individuals.
Ambitions for 2010
• Dissect the molecular mechanisms for sorting to the intracellular antigen loading
compartment in antigen presenting cells.
• Establish whether there is a connection between Toll-like receptor signalling and
regulation of endosomal protein degradation in immune cells.
Fusion and fission of endosomal organelles in model cells. The green is EEA1-GFP,
red the low PH marker lysotracker red and in one image (left) the z direction is
colorcoded. All images are single pictures from live cell imaging movies (from Skjeldal et
al.,submitted).
18
Our group has since the early nineties tried to understand
the intracellular endocytic pathway and how peptide
loading of the MHC class II complexes is regulated. A
special focus for the group is to elucidate the function
of the invariant chain. This molecule is associated with
MHC II and may regulate the intracellular pathway that
facilitate antigen loading. The Bakke group runs the
FUGE imaging facility, NorMIC-UiO, at the University of
Oslo. This core unit is used by CIR and other groups for a
wide variety of projects.
The group is focussing on the endosomal pathway in
cells and particular in immune cells. The projects can be
divided into four sub themes i) Study sorting and traffic
of immune molecules in model cell lines and in dendritic
cells ii) Elucidating the regulation of vesicular traffic
between Golgi and the endosomal pathway, in particular
adaptor proteins, Rabs etc, (Progida et al., JCS in press)
iii) Study how molecules can be sorted to the antigen
loading compartment via specific fusion and fission events
(Skjeldal et al., submitted, figure page 18) iv) Study links
between receptor signalling and the endosomal pathway.
Our work is basic research aiming at understanding the
process of antigen processing and presentation, a process,
which is instrumental for regulating a specific immune
response. In addition the group is collaborating in several
studies where we provide the cell biological and imaging
expertise. We have today a relatively good knowledge
of cell biological processes in model cell lines and the
aim is to find features that are different and specific for
an antigen-presenting cell. To be able to do this work,
we have established many microscopic techniques; in
particular live imaging and essential biochemistry, antigen
presentation and DNA/RNA techniques. We have earlier
studied model cells but the last years we have introduced
professional antigen presentation cells such as dendritic
cells, and the aim is to characterise cell biological aspects
of these cells to better understand vaccination regimes and
protocols for immune therapy of cancers. When immune
molecules such as the MHC class II associated invariant
chain is expressed in model cells this transforms the cell.
The properties of the endosomal pathway are altered from
a degradation pathway into a slowly processing pathway
that can process antigens to peptides that will fit into the
groove of MHC class II molecules (see Landsverk et al.,
2009).
Guest researcher, visiting professor. Prof Terje Espevik,
NTNU, Trondheim has been a visitor in 2008 and 2009.
Work from this period is submitted.
Landsverk OJ, Bakke O, Gregers TF (2009) “MHC II and
the endocytic pathway: regulation by invariant chain”
Scand J Immunol, 70 (3), 184-93
Wegener CS, Malerød L, Pedersen NM, Prodiga C,
Bakke O, Stenmark H, Brech A (2010) ”Ultrastructural
characterization of giant endosomes induced by GTPasedeficient Rab5” Histochem Cell Biol, 133 (1), 41-55
19
Guest professor program
The centre has a comprehensive international outreach. A very important element of CIR’s
activity is the extensive relations we have formed with five world leading scientist. These
researchers spend a week at the centre and during this time give lectures, provide input to the
centres research and participate in supervising PhD students and post docs. Each researcher
is hosted by one of the five groups. The first visit was in December 2008 and the four others
during 2009. They are scheduled to visit the centre again in 2010.
Maria Rescigno
In December 2008 Maria Rescigno visited the centre.
She is at the Department of Experimental Oncology
at the European Institute of Oncology in Milan, Italy.
She is focusing her research on understanding basic
mechanisms of intestinal dendritic cell function in biology
and pathology. Dendritic cells play a primary role in
pathogen protection, in central and peripheral tolerance
and in anticancer immune responses. The title of her guest
lecture was “Dendritic cells in the gut: directors or players
of the immune response?” During her stay a workshop
on imaging techniques was arranged and in addition to
her, other lecturers were invited as well (more details are
found in the 2008 Annual report). Her next visit to the
centre is scheduled to October 2010.
Richard Blumberg
Richard Blumberg visited the centre in February 2009.
He is chief of the Gastroenterology Division at the
Department of Medicine at Brigham and Women’s
Hospital at Harvard Medical School in Boston, USA. His
research area is mucosal immunity and he is interested in
the physiological processes that lead to the development
of inflammatory bowel disease, the management of the
luminal microbial ecology, intestinal barrier dysfunction
and allergy. The title of his guest lecture was “Endoplasmic
Reticulum Stress and Intestinal Inflammation”. During his
visit, an inflammatory bowel disease mini symposium with
other invited lecturers was arranged (see more details on
page 22). Blumberg has published several papers in 2009
in cooperation with scientists at CIR. Shuo-Wang Qiao,
Jan Terje Andersen and Inger Sandlie are engaged in
ongoing collaboration with Richard Blumberg in studies
of the neonatal Fc receptor. Blumberg plans on visiting
the centre again in september 2010.
Jacques Neefjes in discussion with researchers at CIR. (Photo: Oddmund Bakke)
20
Maria Rescigno
Richard Blumberg
Jacques Neefjes
Jacques Neefjes
During March 2009, Jacques Neefjes visited the centre. He
works at the Division of Cell Biology at the Netherlands
Cancer Institute in Amsterdam. His work focuses on
studying the cell biology of MHC class I and MHC
class II molecules. His group has developed fluorescent
techniques to approach single cell biochemistry, and use
combinations of cell biology, chemistry and biophysics to
visualize biochemical reactions in living cells. The title of
his guest lecture was “High throughput analysis of MHC
class II antigen presentation and how to make sense of
it”. He is scheduled to revisit the centre in March 2010.
Mark Shlomchik
Mark Shlomchik
Kai Wucherpfennig
Kai Wucherpfennig
In September 2009 Kai Wucherpfennig visited the centre.
He is working at the Department of Cancer Immunology
& AIDS at the Dana-Farber Cancer Institute at Harvard
Medical School in Boston, USA. His lab seeks to
understand the mechanisms of T-cell recognition and
function by examining the mechanisms of T-cell receptor
assembly and triggering using molecular, structural and
cellular approaches. They also study the causes of T-cell
mediated autoimmune diseases, in particular multiple
sclerosis and type 1 diabetes. During his visit he was the
fist opponent at Lars Egil Fallang’s dissertation. The title
of his guest lecture was “The Earliest Events in T-cell
Activation”. Kai Wucherpfennig will be invited to revisit
the centre.
The centre was visited by Mark Shlomchik in May 2009.
He works at the Laboratory Medicine and Immunobiology
at Yale School of Medicine in New Haven, USA. The main
interest of his lab includes the regulation of auto reactive
B lymphocytes and the development of high affinity B
cell immune responses and memory cells. Lately they
have also started looking at he mechanisms by which T
cells are activated in graft vs. host disease and the subsets
of T cells that are pathogenic. In all their work they
have emphasized in vivo models. The title of his guest
lecture was “Development and Function of Memory B
Cells”. During his visit a workshop on autoimmunity and
autoimmune diseases was arranged, also inviting other
lecturers (see more details on page 22). Bjarne Bogens
group has initiated collaboration with Mark Shlomchik
that concerns the mechanism of action of hemagglutin
vaccibodies for influenza. Mark Shlomchik is also involved
in collaboration with Roberto Di Niro and Ludvig Sollid
studying the anti-transglutaminase antibody response in
coeliac disease. Roberto Di Niro visited Shlomchik’s lab
for 2 weeks in October 2009. Shlomchik is revisiting the
centre in May 2010.
8
21
Minisymposium and Workshop
Minisymposium:
Inflammatory bowel disease
Workshop:
Autoimmunity and autoimmune diseases
Rick Blumberg is a world renowned mucosal
immunologist and past president of the international
Society for Mucosal Immunology, and he is also chief of
the Gastroenterology Division at Brigham & Women’s
Hospital. During his visit, CIR therefore organised
a minisymposium on inflammatory bowel disease
(IBD), a major gastrointestinal disease were he has
considerable expertise. Although the aetiology of IBD is
incompletely understood, the disease is generally believed
to be triggered by environmental factors in genetically
susceptible individuals. An excessive or aberrant immune
response to intestinal non-pathogenic bacteria appears to
be a major driver of IBD. In addition to the main talk
on IBD pathogenesis by Rick Blumberg, senior scientists/
clinicians Jørgen Jahnsen and Knut Lundin gave
overviews of treatment goals and emerging therapies in
IBD. Finally, three young scientists from the region were
given the opportunity to present the latest results of their
own research in IBD. The good attendance of the seminar
from both basic scientists and by clinicians/researchers
underscores that there is an interest in understanding
basic immunology of disease among clinicians and an
interest in understanding and seeing the clinical problems
at hand from basic scientist in CIR and other immunology
groups in the Oslo area.
Chairman: Alexandre Corthay, CIR
Mark Shlomchik is a professor at Yale School of
Medicine, USA. He is a world-leading specialist of B
cells, particularly of the regulation of autoreactive B
lymphocytes and the development of high affinity B cell
immune responses and memory cells. Mark Shlomchik’s
visit at CIR was an excellent opportunity to organise a
workshop on autoimmunity and autoimmune diseases.
Autoimmunity is the failure of an organism to recognise
its own constituent parts as self, which allows an immune
response against its own cells and tissues. Any disease that
results from such an aberrant immune response is termed
an autoimmune disease. Prominent examples include
coeliac disease, diabetes mellitus type 1, systemic lupus
erythematosus, and rheumatoid arthritis. The etiology of
these diseases is largely unknown. A characteristic feature
of autoimmunity is the presence of self-reactive antibodies.
In the workshop’s main lecture, Mark Shlomchik
presented some exciting new data on the role of toll-like
receptors TLR7 and TLR9 for autoantibody production
and disease in a murine model of lupus. Four “local”
speakers reported their latest findings on the pathological
mechanisms leading to autoimmunity. The workshop was
well attended and it generated a stimulating discussion.
Arranged February 27th 2009
Lecturers:
Richard S. Blumberg, Brigham & Women’s Hospital,
Harvard Medical School, Boston, and visiting professor,
Centre for Immune Regulation. Topic “IBD pathogenesis”
Jørgen Jahnsen, Aker University Hospital, Oslo. Topic
“Treatment goals for IBD”
Knut Lundin, Rikshospitalet University Hospital, Oslo.
Topic “Current and emerging therapies for IBD”
Ingrid Olsen, National Veterinary Institute, Oslo.
Topic “Isolation of Mycobacterium avium subspecies
paratuberculosis-reactive T cells from intestinal biopsies
of Crohn’s disease patients”
Gøri Perminov, Ahus University Hospital. Topic “Mucosal
macrophages and regulatory T cells in pediatric IBD”
Jon Sponheim, Rikshospitalet University Hospital, Oslo.
Topic ”Interleukin-33 in IBD”
22
Arranged May 15th 2009
Lecturers:
Mark Shlomchik, Yale University School of Medicine,
New Haven, CT, USA, and visiting professor, Centre for
Immune Regulation. Topic “Activating Autoreactive B
Cells: Roles of Tolls, T Cells, and Time”
Ludvig Munthe, CIR, Institute of Immunology, Oslo
University Hospital, Rikshospitalet. Topic “Idiotypes, T-B
cell collaboration and autoimmune disease”
Kristin Aas-Hanssen, CIR, Institute of Immunology,
University of Oslo and Oslo University Hospital,
Rikshospitalet. Topic “Molecular characteristics of antiDNA antibodies in a mouse model for SLE”
Kristian Hannestad, Institute of Immunology, Oslo
University Hospital, Rikshospitalet. Topic “Antinucleosomal antibodies in a mouse model for SLE”
Trygve Holmøy, Oslo University Hospital, Ullevål. Topic
“The immunology of multiple sclerosis”
Guest lectures
In addition to lectures given by the guest professors
visiting CIR during 2009, two other professors gave
lectures at CIR.
Prof. Jeffrey V. Ravetch gave a guest lecture at CIR
Thursday May 7th, and the title of his talk was “Novel
roles for IgG glycans”. Prof. Ravetch’s is working at
The Rockefeller University, New York, USA.
His
research has contributed to our understanding on how
immunoglobulin G receptors (FcgammaRs) mediate
antibody-triggered inflammation and effector functions
and he has determined the mechanism by which
intravenous immunoglobulin causes immunosuppression.
Prof. Hidde Ploegh gave a guest lecture at CIR Wednesday
March 18th, and the title of his talk was “Interplay
between immunity and infectious agents”. Prof. Ploegh
is working at the Whitehead Institute for Biomedical
Research, Boston, USA. His research has contributed
significantly to our understanding of the mechanism by
which dendritic cells sense the presence of antigens and
instruct the immune response, and he has discover how
a certain set of glycoproteins help the immune system
recognize invaders such as bacteria.
The guest lectures by Ravetch and Ploegh were part of a
guest lecture series organised by a postdoc committee at
CIR.
Guest researchers
Alessandra Camarca
During March and April 2009 Alessandra Camarca
visited the centre. She is a post doc in the laboratory of
Carmen Gianfrani at the Institute of Food Sciences, CNR
Avellino, Avellino, Italy. In Carmen Gainfrani’s lab they
are studying cellular and molecular mechanisms leading
to coeliac disease. Recently, they have also been interested
in the immunopathogenesis of cow’s milk allergy.
Terje Espevik
From September 2008 to June 2009 professor Terje
Espevik was a visitor at the centre. Terje Espevik, is from
the Norwegian University of Science and Technology
and he and his group are focussing on toll like receptors
and their intracellular trafficking and signalling. During
his stay he performed hands on experiments imaging
Toll-like receptors in the cell and the results from this
collaborative effort is submitted and under revision in a
prestigious journal.
23
Internal activities
Project meetings
To keep the members of the centre up to date on
the research within the centre, project meetings are
arranged monthly. Each meeting, one of the five groups
is responsible for presenting a project. During 2009 nine
project meetings were organized. Typically unpublished
data from one or two projects are presented. Presentations
range from discussion of technical challenges, via
preliminary data to publication ready work. Ample time
is reserved for discussion following the presentations and
discussion is encouraged. At the end of the meeting snacks
and soft drinks is served to promote interaction and to
continue the discussion in a less formal atmosphere. The
project meeting is an important event that facilitates
collaboration, idea generation and critical discussion.
Furthermore, these meetings provide a friendly venue for
junior scientists less experienced in presenting their own
work. The project meeting is also a vital activity aiming to
build centre identity and sense of community.
CIR literature seminar for young researchers
The seminars were initiated in 2008 and master students,
PhD students as well as postdocs/young researchers
are invited. The aim is to achieve training in critical
evaluation of scientific articles as well as to stimulate
students to actively participate in scientific discussions.
Eight seminars were held in 2009. Articles were picked
from journals such as Nature Medicine, Science, and
Immunity. Based on the selected articles, the seminars
included topics such as: precursors and development of
dendritic cells; conventional CD4+ T cells (Th1, Th2) can they both activate and suppress; the danger model
and NLRP3 inflammasomes; and causal relationship
between disease and pathogens. The seminar series will
continue and it is planned to arrange nine meetings
throughout 2010.
CIR annual retreat
CIR arranged a retreat in December 2008. The next
retreat was postponed to April 2010 to be able to meet
at a winter resort during snow season, but avoiding the
hectic December month. The next retreat will be arranged
at Dr Holms Hotel at Geilo 14-16 April 2010.
Inflammation in the colon of a triply transgenic mouse. Complement deposition (red), activated NF-kB dependent
luciferace (green) and nuclei (blue). (Photo: Ludvig Munthe).
24
Education and career progression
Educated PhD’s
Career progression
Three theses were defended in 2009.
Anders Sandvik, “A study on immunomodulating betaglucan: Effects of oral application on inflammation, tissue
injury, and the mucosal immune system in experimental
animals”.
Lars-Egil Fallang, “Investigating celiac disease using
recombinant soluble MHC class II molecules”.
Michael M. Zangani, “Idiotope Driven T-B Collaboration
– Autoimmunity and Lymphomagenesis”.
Educated masters
During 2009 seven master students and medical students
graduated.
Within CIR nine people have advanced in their careers
during 2009. Head physician Frode Jahnsen has become
a professor. Resident Ludvig A. Munthe and post doc
Shuo-Wang Qiao have become assistant professors.
Ludvig started his new position during 2009 and ShuoWang started January 1st 2010. Anders Sandvik defended
his PhD and continued as a post doc in the same group.
Axel Berg-Larsen and Ole-Audun W. Haabeth finished
their master study and continued as PhD students. Axel
Berg-Larsen changed group within the centre and OleAudun W. Haabeth continued in the same group. Kristina
B. Lorvik worked is a technician and is also a former
master student and has started as a PhD student in the
same group. Ana Kucera and Lene Støkken Høydahl
finished their master study and have continued in their
respective groups as technicians.
Gender equality program
Mentoring program
At the centre and generally in molecular biomedical
research there is a high proportion of female PhD
students and postdocs, while most of the senior
scientists and group leaders are male. Mentoring is
known to improve career satisfaction and thereby
helping to increase recruitment. CIR has therefore
initiated a mentoring program for female postdocs. At
the onset of the program, CIR had a total of 17 female
postdocs, and 10 accepted the invitation to join the
program. A total of five mentors, one man and four
women, were chosen among senior faculty at The
University of Oslo. The postdocs preferred established
postdoc-mentor pairs, and therefore, each postdoc was
assigned the mentor of her choice. All mentors and
postdocs met for a half day seminar at the outset of
the program, where one of the postdocs described her
expectations and the mentors spoke of their interest
in the program and how they would contribute. The
mentor-postdoc pairs will meet on a regular basis, and
the program continues in 2010.
Technical assistance
A female postdoc must often balance research at the bench
with family responsibilities. In 2009, a total of four female
postdocs that were on or just returning from maternity
leave, were assigned full time technical assistance on their
projects. The postdocs applied to the program, and each
application included a project description as well as a
candidate for the job, chosen among the MSc students
at CIR. In the application they also described how they
would communicate with and guide the assistant while
on maternity leave. We consider this to be a success and
will continue the program in 2010.
25
Management and boards
Management
CIR is a consortium of two partners, the University of Oslo (host organization), and Oslo
University Hospital Rikshospitalet. The centre is lead by Professors Ludvig Sollid (Director)
and Inger Sandlie (Assistant Director), whereas Elin Lunde was the administrative leader.
During 2009, Anders Sandvik was acting administrative leader, and Stine Bergholtz took
over the position January 1st 2010. There are five research groups in CIR, lead by professors,
Ludvig Sollid (includes the group of Burkhard Fleckenstein), Inger Sandlie, Oddmund
Bakke, Bjarne Bogen and Finn-Eirik Johansen (includes the group of Frode Jahnsen). The
group leaders meet for decision making on a regular basis. In total, around 100 persons
are involved in research at CIR. CIR’s activities are located in the Research Building at
the Oslo University Hospital Rikshospitalet, and in Kristine Bonnevie’s Building at the
University Campus at Blindern.
The CIR board
The governing board of CIR has four members; two from
the University of Oslo (UiO) and two from Rikshospitalet
University Hospital (RH).
• Sigbjørn Fossum (chair), Dean of Research, Faculty
of Medicine, UiO
• Anders Elverhøi, Dean of Research, Faculty of
Mathematics and Natural Sciences, UiO
• Inger Nina Farstad, Head of the Clinic of Pathology,
RH
• John Torgils Vaage, Head of the Clinic of Laboratory
Medicine, RH
The board ensures that the intentions and plans underlying
the contract are fulfilled, and that the activities discussed
in the project description and funding plan are completed
within the adopted time frame. The board further ensures
that the interaction between CIR, the host institution and
the consortium partner functions efficiently. An important
role for the board in the early phase was to ensure that the
question of co-localization was followed adequately up by
the consortium partners. The Board held two meetings in
2009, on January 26th and June 8th.
26
The scientific advisory board
The scientific advisory board has three members:
• Prof. Søren Buus, University of Copenhagen,
Denmark
• Prof. Rikard Holmdahl, Karolinska Institutet,
Stockholm, Sweden
• Prof. Sirpa T. Jalkanen, University of Turku, Finland
The role for the scientific advisory board is to critically
evaluate and advise on the centre’s scientific performance.
In order to assess recent progress and future strategies,
the scientific advisory board will meet with the centre
annually. This annual meeting will occur at the CIR annual
retreat. The 2009 annual retreat has been postponed to
April 2010.
Appendix 1
CIR staff and students
29
Personnel per Dec 31st 2009
30
26
25
19
20
15
11
10
5
9
5
1
0
Administration
PhD students
Post docs
Group leaders
Researchers
Students
Technicians
Group leaders
Name
Position
Funding*
Employer*
Oddmund Bakke
Professor
UiO
UiO
Bjarne Bogen
Professor
UiO/RH
UiO/RH
Finn-Eirik Johansen
Professor
UiO/RH
UiO/RH
Inger Sandlie
Professor
UiO
UiO
Ludvig Sollid
Professor
RCN
UiO/RH
Name
Position
Funding*
Employer*
Per Brandtzæg
Professor emeritus
Espen Bækkevold
Researcher
HRSE
RH
Alexandre Corthay
Researcher
NCS
UiO
Burkhard Fleckenstein
Researcher
UiO
UiO
Frode Jahnsen
Professor
UiO/RH
UiO/RH
Katrin Lundin
Resident
RH
RH
Knut EA Lundin
Chief physician
RH
RH
Øyvind Molberg
Resident
RH
RH
Ludvig A Munthe
Assistant professor
RH
RH
Ingrid Olsen
Veterinary Broad Institute
RH
Keith Thompson
Researcher
UiO
UiO
Research Scientists
27
PhD students
Name
Funding*
Employer*
Christina Bang
HRSE
RH
Ann-Christin R. Beitnes
RH
RH
Axel Berg-Larsen
UiO
UiO
Michael Bodd
H&R
RH
Muluneh Bekele Daba
UiO
UiO
Siri Dørum
RCN
UiO
Alexander Erofeev
RCN
UiO
Terje Frigstad
RCN
UiO
Gunnveig Grødeland
RCN
UiO
Kristin Gunnarsen
RCN
UiO
Ingvild Heier
UUH
UUH
Rejoanoul (“Reza”) Islam
EU
UiO
Rasmus Iversen
UiO
UiO
Johanne Jacobsen
UiO-EMBIO
UiO
Synne Jenum
RCN
UiO
Ulrike Jüse
HRSE
UiO
Ole J. B. Landsverk
UiO
UiO
Kristina B. Lorvik
HRSE
UiO
Guro Reinholt Melum
HRSE
RH
Luka Mesin
EU
UiO
Audun Os
UiO
UiO
Dag Henrik Reikvam
NCS
UiO
Tahira Riaz
HRSE
RH
Pier A. Ruffini
NCS
RH
Ingebjørg Skrindo
UiO
UiO
Jorunn Stamnæs
UiO
UiO
Astrid E. V. Tutturen
UiO-EMBIO
UiO
Kristine Ustgård
UiO
UiO
Kristin Aas-Hanssen
UiO
UiO
28
Postdocs
Name
Funding*
Employer*
Silja S. Amundsen
HRSE
RH
Jan Terje Andersen
RCN
UiO
Elin Bergseng
RCN
UiO
Gøril Berntzen
NCS
UiO
Ranveig Braathen
EU/RCN
UiO
Hege Carlsen
RH/RCN
UiO/RH
Elena Danilova
RCN
UiO
Roberto DiNiro
EU
UiO
Anders Fallang
HRSE
RH
Even Fossum
RCN
RH
Agnete B. Fredriksen
NCS
RH
Ane Funderud
HRSE
RH
Tone F. Gregers
RCN
UiO
Shailly N. Gupta
NCS
UiO
Anders Holm
RCN-FUGE
UiO/RH
Denis Khnykin
HRSE
RH
Gerbrand Koster
RCN-FUGE
UiO
Geir Åge Løset
RCN
UiO
Cinzia A. M. Progida
UiO
UiO
Shuo-Wang Qiao
RCN
RH
Melinda Raki
HRSE
RH
Ingunn B. Rasmussen
NCS
UiO
Charlotta Sandin
NCS
RH
Anders Sandvik
Biotec Pharmacon
UiO
Stig Tollefsen
H&R
RH
Inger Øynebråten
RCN
UiO
29
Technicians
Name
Position
Funding*
Employer*
Aaste Aursjø
Bio engineer
UiO
UiO
Hege Eliassen
Secretary
RH
UiO
Kathrine Hagelsteen
Bio engineer
UiO
UiO
Linda Haugen
Divisional engineer
UiO
UiO
Beate Hegge
Divisional engineer
RH
RH
Peter O. Hofgaard
Chief engineer UiO
UiO
Lene Støkken Høydahl
Technichian
RCN
UiO
Marie K Johannesen
Chief engineer UiO
UiO
Marit Jørgensen
Bio engineer
HRSE
RH
Mona Lindeberg
Chief engineer VB
RH
Linda Manley
Bio engineer
RH
UiO
Hogne Røed Nilsen
Bio engineer
RH
RH
Hilde Omholt
Chief engineer NCS
RH
Bjørg Simonsen
Divisional engineer
JDRF
RH
Frode M. Skjeldal
Divisional engineer
NCS
UiO
Linda Solfjell
Bio engineer
RH
RH
Kjersti Thorvaldsen
Bio engineer
HRSE
RH
Sathiyaruby M. Vadivelu
Divisional engineer
UiO
UiO
Elisabeth L. Vikse
Divisional engineer
EU
UiO
30
Students
Name
Study
Vedrana Grcic
Master student
Ole-Audun W. Haabeth
Master student
Tom Ole Løvaas
Medical student
Ralf Neumann
Master student
Erlend Pedersen
Master student
Kine Marita Knudsen Sand
Master student
Heidi C. L. Spång
Master student
Ingvild Sørum
Master student
Lise M. Øieren
Master student
Administration
Name
Position
Funding*
Employer*
Stine Bergholtz
Adminstrative leader
CIR
UiO
* EU - European Union
H&R - Norwegian Foundation for Health and Rehabilitation
HRSE - Health Region South East
JDRF - Juvenile Diabetes Research Foundation
NCS - Norwegian Cancer Society
RCN - Research Council of Norway
RCN-FUGE - Funksjonell genomforskning (RCN)
RH - Rikshospitalet University Hospital
UiO - University of Oslo
UiO-EMBIO - Steering board for Molecular Life Sciences (UiO)
UUH - Ullevål University Hospital
VB - Vaccibodies AS
31
Appendix 2
Publications
Papers
Andersen JT, Sandlie I (2009) “The versatile MHC class I-related FcRn protects IgG and albumin from degradation:
implications for development of new diagnostics and therapeutics” Drug Metab Pharmacokinet, 24 (4), 318-32
Baker K, Qiao SW, Kuo T, Kobayashi K, Yoshida M, Lencer WI, Blumberg RS (2009) “Immune and non-immune
functions of the (not so) neonatal Fc receptor, FcRn” Semin Immunopathol, 31 (2), 223-36
Berntzen G, Andersen JT, Ustgård K, Michaelsen TE, Mousavi SA, Qian JD, Kristiansen PE, Lauvrak V, Sandlie I
(2009) ”Identification of a high affinity FcgRIIA-binding peptide that distinguishes FcgRIIA from FcgRIIB and exploits
FcgRIIA-mediated phagocytosis and degradation” J Biol Chem, 284 (2), 1126-35
Bethune MT, Crespo-Bosque M, Bergseng E, Mazumdar K, Doyle L, Sestak K, Sollid LM, Khosla C (2009)
“Noninflammatory gluten peptide analogs as biomarkers for celiac sprue” Chem Biol, 16 (8), 868-81
Bogen B, Ruffini P (2009) “Review: to what extent are T cells tolerant to immunoglobulin variable regions?” Scand J
Immunol, 70 (6), 526-30
Brandtzaeg P (2009) “Mucosal immunity: induction, dissemination, and effector functions” Scand J Immunol, 70 (6),
505-15
Brandtzaeg P (2009) “‘ABC’ of mucosal immunology” Nestle Nutr Workshop Ser Pediatr Program, 64, 23-38; discussion
38-43, 251-7
Corthay A (2009) “How do regulatory T cells work?” Scand J Immunol, 70 (4), 326-36
Corthay A, Lundin KU, Lorvik KB, Hofgaard PO, Bogen B (2009) “Secretion of tumor-specific antigen by myeloma
cells is required for cancer immunosurveillance by CD4+ T cells” Cancer Res, 69 (14), 5901-7
Dørum S, Qiao SW, Sollid LM, Fleckenstein B (2009) “ A quantitative analysis of transglutaminase 2-mediated
deamidation of gluten peptides: implications for the T-cell response in celiac disease” J Proteome Res, 8 (4), 1748-55
Fallang LE, Bergseng E, Hotta K, Berg-Larsen A, Kim CY, Sollid LM (2009) ”Differences in the risk of celiac disease
associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation” Nat Immunol, 10
(10), 1096-101
Funderud A, Aas-Hanssen K, Aksaas AK, Hafte TT, Corthay A, Munthe LA, Orstavik S, Skålhegg BS (2009) “Isoformspecific regulation of immune cell reactivity by the catalytic subunit of protein kinase A (PKA)” Cell Signal, 21 (2),
274-81
Gabbard J, Velappan N, Di Niro R, Schmidt J, Jones CA, Tompkins SM, Bradbury AR (2009) “A humanized anti-M2
scFv shows protective in vitro activity against influenza” Protein Eng Des Sel, 22 (3), 189-98
Ghumra A, Shi J, Mcintosh RS, Rasmussen IB, Braathen R, Johansen FE, Sandlie I, Mongini PK, Areschoug T, Lindahl
G, Lewis MJ, Woof JM, Pleass RJ (2009) ”Structural requirements for the interaction of human IgM and IgA with the
human Fca/m receptor” Eur J Immunol, 39 (4), 1147-56
Halvorsen EH, Haavardsholm EA, Pollmann S, Boonen A, van der Heijde D, Kvien TK, Molberg Ø (2009) “Serum
IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis
treated with tumour necrosis factor-a blocking agents” Ann Rheum Dis, 68 (2), 249-52
Hol J, Küchler AM, Johansen FE, Dalhus B, Haraldsen G, Oynebråten I (2009) ”Molecular requirements for sorting of
the chemokine interleukin-8/CXCL8 to endothelial Weibel-Palade bodies” J Biol Chem, 284 (35), 23532-9
32
Holt PG, Strickland DH, Bosco A, Jahnsen FL (2009) “Pathogenic mechanisms of allergic inflammation: Atopic
asthma as a paradigm” Adv.Immunol., 104, 51-113
Jabri B, Sollid LM (2009) “Tissue-mediated control of immunopathology in coeliac disease” Nat Rev Immunol, 9 (12),
858-70
Jüse U, Fleckenstein B, Bergseng E, Sollid LM (2009) ”Soluble HLA-DQ2 expressed in S2 cells copurifies with a high
affinity insect cell derived protein” Immunogenetics, 61 (2), 81-9
Kobayashi K, Qiao SW, Yoshida M, Baker K, Lencer WI, Blumberg RS (2009) “An FcRn-dependent role for antiflagellin immunoglobulin G in pathogenesis of colitis in mice” Gastroenterology, 137 (5), 1746-56.e1
Landsverk OJ, Bakke O, Gregers TF (2009) “MHC II and the endocytic pathway: regulation by invariant chain” Scand
J Immunol, 70 (3), 184-93
Lång E, Haugen K, Fleckenstein B, Homberset H, Frye SA, Ambur OH, Tønjum T (2009) “Identification of neisserial
DNA binding components” Microbiology, 155 (Pt 3), 852-62
Michaelsen TE, Sandlie I, Bratlie DB, Sandin RH, Ihle O (2009) ”Structural difference in the complement activation
site of human IgG1 and IgG3” Scand J Immunol, 70 (6), 553-64
Olsen I, Tollefsen S, Aagaard C, Reitan LJ, Bannantine JP, Andersen P, Sollid LM, Lundin KE (2009) “Isolation of
Mycobacterium avium subspecies paratuberculosis reactive CD4 T cells from intestinal biopsies of Crohn’s disease
patients” PLoS One, 4 (5), e5641
Perminow G, Reikvam DH, Lyckander LG, Brandtzaeg P, Vatn MH, Carlsen HS (2009) “Increased number and
activation of colonic macrophages in pediatric patients with untreated Crohn’s disease” Inflamm Bowel Dis, 15 (9),
1368-78
Qiao SW, Sollid LM, Blumberg RS (2009) “Antigen presentation in celiac disease” Curr Opin Immunol, 21 (1), 111-7
Schiøtz BL, Baekkevold ES, Poulsen LC, Mjaaland S, Gjøen T (2009) ”Analysis of host- and strain-dependent cell
death responses during infectious salmon anemia virus infection in vitro” Virol J, 6, 91
Smits HH, Gloudemans AK, van Nimwegen M, Willart MA, Soullié T, Muskens F, de Jong EC, Boon L, Pilette C,
Johansen FE, Hoogsteden HC, Hammad H, Lambrecht BN (2009) “Cholera toxin B suppresses allergic inflammation
through induction of secretory IgA” Mucosal Immunol, 2 (4), 331-9
Sollid LM, Lundin KE (2009) “Diagnosis and treatment of celiac disease” Mucosal Immunol, 2 (1), 3-7
Stenman SM, Venäläinen JI, Lindfors K, Auriola S, Mauriala T, Kaukovirta-Norja A, Jantunen A, Laurila K, Qiao
SW, Sollid LM, Männisto PT, Kaukinen K, Mäki M (2009) “Enzymatic detoxification of gluten by germinating wheat
proteases: implications for new treatment of celiac disease” Ann Med, 41 (5), 390-400
Stensland M, Holm A, Kiehne A, Fleckenstein B (2009) ”Targeted analysis of protein citrullination using chemical
modification and tandem mass spectrometry” Rapid Commun Mass Spectrom, 23 (17), 2754-62
Stensland ME, Pollmann S, Molberg Ø, Sollid LM, Fleckenstein B (2009) ”Primary sequence, together with other
factors, influence peptide deimination by peptidylarginine deiminase-4” Biol Chem, 390 (2), 99-107
33
Stronen E, Abrahamsen IW, Gaudernack G, Wälchli S, Munthe E, Buus S, Johansen FE, Lund-Johansen F, Olweus J
(2009) “Dendritic cells engineered to express defined allo-HLA peptide complexes induce antigen-specific cytotoxic T
cells efficiently killing tumour cells” Scand J Immunol, 69 (4), 319-28
Zangani M, Carlsen H, Kielland A, Os A, Hauglin H, Blomhoff R, Munthe LA, Bogen B (2009) “Tracking early
autoimmune disease by bioluminescent imaging of NF-kappaB activation reveals pathology in multiple organ systems”
Am J Pathol, 174 (4), 1358-67
Books and book chapters
Andersen J. T. and Sandlie I., Bookchapter: “Extending Antibody Fragment Half-Lives with Albumin” Recombinant
Antibodies for Immunotherapy, Edited by Melvyn Little, Affimed Therapeutics AG, Cambridge University Press 2009
Andersen J. T. and Sandlie I., Bookchapter: “The neonatal Fc receptor controls immunoglobulin G and albumin
homeostasis” Hepatic endocytosis, Edited by Marita Sporstøl Fønhus, Seyed A. Mousavi og Trond Berg, Transworld
Research Network 2009
Brandtzaeg P, Isolauri E, Prescott SL (Editors): Microbial–Host Interaction: Tolerance versus Allergy. Nestlé Nutr. Inst.
Workshop Ser. Pediatr. Program 64, Nestec Ltd., Vevey/S, Karger AG, Basel, 2009, pp. 271
Brandtzaeg P: Mucosal immunity: from allergy to coeliac disease. pp. 529-561. In: Allergy Frontiers: Classification and
Pathomechanisms (Ed.: Pawankar R, Holgate ST, Rosenwasser LJ). Springer, Berlin, 2009
Brandtzaeg P: ‘ABC’ of Mucosal Immunology. pp. 23-43. In: Microbial–Host Interaction: Tolerance versus Allergy
(Eds.: Brandtzaeg P, Isolauri E, Prescott SL). Nestlé Nutr. Inst. Workshop Ser. Pediatr. Program 64: 23–43, Nestec Ltd.,
Vevey/S, Karger AG, Basel, 2009
Prescott SL, Brandtzaeg P, Isolauri E: Summary. pp. 251-257. In : Microbial–Host Interaction: Tolerance versus Allergy.
Nestlé Nutr. Inst. Workshop Ser. Pediatr. Program 64: 251-257, Nestec Ltd., Vevey/S, Karger AG, Basel, 2009
Brandtzaeg P, Isolauri E, Prescott SL: Concluding remarks. pp. 259-266. In : Microbial–Host Interaction: Tolerance
versus Allergy. Nestlé Nutr. Inst. Workshop Ser. Pediatr. Program 64: 259-266, Nestec Ltd., Vevey/S, Karger AG, Basel,
2009
Brandtzaeg P: Overview of the innate and adaptive mucosal immune system: Linking immune development in the gut
to other mucosal sites and the periphery. pp. 1-13. In: Mucosal Immune Development and Dietary Influences (Ed.:
Gussler J), Report of the 109th Abbott Nutrition Research Conference, Columbus, Ohio: Abbott Nutrition, 2009
Løset GÅ, Mousavi SA and Berg T., Bookchapter: “Sinusoidal liver cells and liver tolerance” Hepatic endocytosis,
Edited by Marita Sporstøl Fønhus, Seyed A. Mousavi og Trond Berg, Transworld Research Network 2009
34
Appendix 3
Presentations given outside CIR
Invited lectures
Oddmund Bakke: “Dramatic alterations of the endosomal pathway after Salmonella- invasion in epithelial cells”
Prophylactic & Therapeutic Intervention in Host-Pathogen Interaction June 5-8, 2009, LO-Skolen, Helsingør, Denmark.
Oddmund Bakke: “Imaging the endosomal pathway - an overview” The endocytic pathway in health an disease,
Workshop, March18-21st, 2009, Voss, Norway.
Bjarne Bogen: ” Imaging of autoimmunity in a transgenic model” Oslo Transgenic Mouse Meeting, Lysebu, Oslo, Sept
4th, 2009.
Bjarne Bogen: “Kreftvaksiner – hvor star vi hen?” I programmet ”Immunforsvaret og kreft – fra forskning til klinikk”.
Immunologiens dag April 24, 2009. Gamle festsal, Universitetet i Oslo.
Bjarne Bogen: “Recombinant immunoglobulin-like vaccine molecules that target APC for enhanced immunogenicity.”
Lecture Workshop. The endocytotic pathway in health and disease. Voss, Norway, March 18-21, 2009.
Per Brandtzæg: “ Tarmens immunsystem - på godt og vondt” Årsmøte i Norsk selskap for klinisk ernæring (NSKE),
Oslo, January 15, 2009.
Per Brandtzæg: “Secretory immunity, memory and homeostasis at mucosal surfaces”, World Immune Regulation-III,
Davos, Sveits, March 24, 2009.
Per Brandtzæg: “Hva vet vi om lokal immunitet ved systemisk HPV-vaksinering?”, Møte om ”HPV-vaksine i
barnevaksinasjonsprogrammet”, Bioteknologinemda, Oslo., April 1, 2009.
Per Brandtzæg: “The mucosal immune system”.“Kick-off Meeting, Marie Curie Initial Training Network, Cross-Talk
(EUs 7. rammeprogram), Paris., April 28, 2009.
Per Brandtzæg: “Mucosal immunity: induction, dissemination, and effector functions”, Master Class, Postgraduate
School, Universitetet i Hannover, Hannover, Tyskland. June 4, 2009.
Per Brandtzæg: “Microbes and the mucosal immune system”, Nobel-miniseminar “In Focus: Gut Microbes and
Functions in Health and Disease”, Karolinska Institutet, Stockholm. June 10, 2009.
Per Brandtzæg: “Preventing a genital mucosal infection: systemic or mucosal immunization?”, Kreftregisteret, Oslo.
June 19, 2009.
Per Brandtzæg: “Brainstorming session: Regulatory Cells which Control Mucosal Immunity & Inflammation; 14th
International Congress of Mucosal Immunology (ICMI 2009), Society for Mucosal Immunology (SMI), Boston, USA.,
July 8, 2009 (Cairmans introduction).
Per Brandtzæg: “The mucosal barrier: immune defence and inflammation.” , Flamsk seksjon, Belgisk forening for
pediatri, Oslo. September 11, 2009.
Per Brandtzæg: “Hypersensitivity and tolerance in the absence of a secretory immune system.” Session WSLB06:
Inflammatory Diseases, 2nd European Congress of Immunology, Berlin. September 16, 2009, (Lecture as chairman).
Per Brandtzæg: “The mucosal barrier: immune defence and inflammation.” Invitert foredrag, Fransk seksjon, Belgisk
forening for pediatri, Oslo. September 25, 2009.
Per Brandtzæg: “Allergi – hvorfor øker forekomsten?” , Årsmøte i Den norske tannlegeforening, Lillestrøm. October
15, 2009.
Per Brandtzæg: “Induction and function of the mucosal immune system”, Plenary 03: B Cell Biology, AIDS Vaccine
2009 Conference, Paris. October 22, 2009.
Per Brandtzæg: “Homeostatic impact of indigenous microbiota and secretory immunity.”, XXXII SOMED Congress,
Society for Microbial Ecology and Disease, St. Petersburg, Russland. October 29, 2009.
35
Per Brandtzæg: “Induction, dissemination and function of mucosal B cells.” Minisymposium: “Vaccination and Mucosal
Immunity”, DWG Vaccines and the Infection & Immunity Center Utrecht (IICU), Utrecht, Nederland. Novmeber 19,
2009.
Per Brandtzæg: “Mucosal immunity: induction of protective and homeostatic mechanisms.”, Bernhard-Nocht-Institute
for Tropical Medicine, University of Hamburg, Hamburg, Tyskland.. Novmeber 24, 2009.
Lene Støkken Høydahl: “Antibody Engineering”. Department of Radiation Biology, Oslo University Hospital, Oslo,
Norway, 8. September 2009.
Frode Jahnsen: “Local traffic of immune cells in the airways” 28th meeting of the European Academy of allergy and
Clinical immunology (EAACI), Warzaw, June 2009.
Finn-Eirik Johansen: “In vivo validation in animal models and alternative human-derived models” Cross Talk Kick Off
Meeting - Paris, France April 29th 2009 - Official day.
Finn-Eirik Johansen: “The polymeric Ig Receptor” 14th International Congress of Mucosal Immunology July 5 – 9,
2009 Boston, USA.
Knut E. A. Lundin: “The diversity of celiac disease”. 13th Int. Coeliac Disease Symposium. Amsterdam, the Netherlands.
April 6-8, 2009.
Knut E. A. Lundin: “Wheat starch and oats: which limitations”. Gastro 2009, UEGW/WCOG - Meeting of the European
Society for the Study of Coeliac Disease (ESSCD). London, United Kingdom. November 21-25, 2009.
Geir Åge Løset: “ T cell receptor engineering: A rational versus a combinatorial approach”. May 23, 2009,
Radiumhospitalet, Oslo.
Ludvig A. Munthe: “Idiotypes, T-B cell collaboration and autoimmune disease.” Norwegian Society of Immunology
(NSI), Gaustad, Oslo, May 2009.
Ludvig A Munthe: “Immunologi og atopi. Th2-celler, B-celler og immunresponsen mot allergener” Atopiforum, Grand
Hotel, Oslo. February 2009.
Ludvig A Munthe: ”Immunologi og huden”, Arranged by Meda AS., Rikshospitalet, Oslo April 2009.
Ludvig A Munthe: ”Immunologi og immunpatologi ved revmatisk sykdom” Foredrag for Revmatologer, Roche.,
Radisson SAS, Oslo, April 2009.
Ludvig A Munthe: “Immunologi, celler, immunrespons og TNF” Schering Plough. Eiksmarka, Bærum. April 2009.
Frode Skjeldal : “Early Endosomal fusion stimulates instantaneous tubular formation and fission”, National NORMIC
user meeting, Stavanger, November, 12-13 2009.
Ingebjørg Skrindo: “Allergi I øvre luftveier” “Nettrundervisning” for doctors specializing in immunologi, Rikshospitalet,
May 14 2009.
Ludvig M. Sollid: “Pathogenesis of celiac disease”. 13
April 6-8, 2009.
th
Int. Coeliac Disease Symposium. Amsterdam, the Netherlands.
Ludvig M. Sollid: “Can mucosa induced T cell responses be assayed in the peripheral blood”. Italian EFIS Day of
Immunology, April 29, 2009, Avellino, Italy.
Ludvig M. Sollid: Broadening Horizons. Single Topic Meeting. American Gastroenterological Association. September
11-12, 2009, Chicago, USA.
Ludvig M. Sollid: “Genetic Basis of Celiac Disease”. Celiac Disease – Broadening Horizons. Single Topic Meeting.
American Gastroenterological Association. September 11-12, 2009, Chicago, USA.
Ludvig M. Sollid: “Functional Immunogenetics of Celiac Disease”. 2nd European Congress of Immunology. Berlin,
Germany. September 13-16, 2009.
36
Ludvig M. Sollid: “Cøliaki og diabetes, likheter i etiologi”. Nasjonalt pediatrimøte. October 12-13, 2009, Sundvolden.
Ludvig M. Sollid: “Sykdomsmekansimen ved cøliaki, Kan sykdommen forhindres?” Phadia brukermøte om
autoimmunitet. November 5, 2009, Oslo.
Ludvig M. Sollid: ”Coeliac disease: Differences in adaptive and innate immunity. The key to phenotypic variation”.
Gastro 2009, UEGW/WCOG. London, United Kingdom. November 21-25, 2009.
Oral presentations
Oddmund Bakke: “Salmonella-containing Vacuoles Consume Late Endosomal / Lysosomal Membranes” NBS contact
meeting, Røros Norway, January 29th –Feb 1st, 2009.
Oddmund Bakke: “EGF signalling and endosomal coat kinetics.” NBS contact meeting, Røros, Norway, January 29th
–Feb 1st, 2009.
Ann-Christin Røberg Beitnes: “CD103+ Dendritic Cells Reside in Human Small Intestinal Mucosa but Do Not Increase
in the Active Celiac Lesion”. NSI-meeting 2009. Oslo, Norway. November 20, 2009.
Michael Bodd: “Intestinal gluten-reactive T cells in celiac disease produce IL-21, but not IL-17”. 13
Disease Symposium. Amsterdam, the Netherlands. April 6-8, 2009.
th
Int. Coeliac
Roberto Di Niro: “Autoantibody profiling of celiac disease by antigen microarrays”. 13th Int. Coeliac Disease Symposium.
Amsterdam, the Netherlands. April 6-8, 2009. �
Siri Dørum: “A quantitative analysis of transglutaminase 2-mediated deamidation of gluten peptides: implications for
the T-cell response in celiac disease”. 13th Int. Coeliac Disease Symposium. Amsterdam, the Netherlands. April 6-8,
2009.
Siri Dørum: “Identification of the best gluten substrates for transglutaminase 2 in proteolytic digest of whole gluten”.
5th Norwegian National Proteomics Meeting, Bergen, Norway, October 26-27, 2009.
Kristin Støen Gunnarsen: “Thermostability engineering of a single chain T cell receptor using phage display”, 2nd
European Congress of Immunology, Berlin, Germany, September 13-16, 2009.
Frode Jahnsen: “Increased recruitment of myeloid dendritic cells in experimentally-induced allergic rhinitis” 28th
meeting of the European Academy of allergy and Clinical immunology (EAACI), Warzaw, June 2009.
Gerbrandt Koster: “Membrane control of dynamin polymerization” The endocytic pathway in health an disease,
Workshop, March 18-21st, 2009, Voss, Norway.
Ole Landsverk: “ Regulation and distribution of CD74 during dendritic cell maturation” The endocytic pathway in
health an disease, Workshop, March 18-21st, 2009, Voss, Norway.
Geir Åge Løset: “Thermostability engineering of a soluble T cell receptor using phage display”. Phage Display of
Therapeutic Antibodies, PEGS Europe 2009 meeting, October 6-8, 2009, Hannover, Germany.
Melinda Ráki: “Flow cytometry”. TRACKS Marie Curie workshop on Immunology and related techniques, August 2426 2009, Tampere, Finland.
Guro Reinholt Melum: “Experimentally induced recruitment of myeloid dendritic cells in upper airway allergy” 7th
EAACI-Ga2len-Davos Meeting 5-8 Februar 2009.
Anders Sandvik: “Oral treatment with soluble beta-glucan protects against experimental ulcerative colitis” World
Immune Regulation Meeting III, The Swiss Institute of Allergy and Asthma Research (SIAF), September 22-23 2009,
Davos.
Frode Skjeldal: “Imaging endosomal fusion and tubulation” The endocytic pathway in health an disease, Workshop,
March 18-21st, 2009, Voss, Norway.
37
Ingebjørg Skrindo: ” Experimentally induced recruitment of Foxp3+ T cells in upper airway allergy” XXVIII EAACI
Congress in Warsaw , Poland, June 8 2009.
Ludvig M. Sollid: “The pathogenesis of celiac disease”. TRACKS Marie Curie workshop on Immunology and related
techniques, August 24-26 2009, Tampere, Finland.
Astrid E.V. Tutturen: “Two novel strategies for the targeted proteomic analysis of protein citrullination”. 5th Norwegian
National Proteomics Meeting, Bergen, Norway, October 26-27, 2009.
Posters
J.T. Andersen, M.B. Daba, G. Berntzen, T.E. Michaelsen, I. Sandlie: ” Cross-species binding analyses of mouse and
human neonatal fc receptor with their ligands: Implications for evaluations of therapeutic antibodies and albumin
fusions” The 2nd European Congress of Immunology, Berlin, September 13 – 16, 2009.
S. Justesen, J.T Andersen, I Sandlie, S. Buus: ” Bacterial expression and refolding of biotinylated neonatal fc receptors
and accompanying high throughput screening assays” The 2nd European Congress of Immunology, Berlin, September
13 – 16, 2009.
N.M. Stapleton, A.M. Stemering, S. Bjarnarson, J.T. Andersen, R.C. Verheul, J. Gerritsen,Y. Zhao, M. Kleijer, I.
Sandlie, M. de Haas, I. Jonsdottir, C.E. van der Schoot,G. Vidarsson: “Extending IGG3 half-life in humans by a single
isoallotypic amino acid substitution for enhanced in vivo therapies” The 2nd European Congress of Immunology,
Berlin, September 13 – 16, 2009.
Silja S. Amundsen: “Exploring novel candidate susceptibility regions in celiac disease (CD) -genetic association mapping
of chr. 3p21.31 in a Scandinavian CD cohort”. 13th Int. Coeliac Disease Symposium. Amsterdam, the Netherlands.
April 6-8, 2009.
Ann-Christin Røberg Beitnes: “CD103+ Dendritic Cells Reside in Human Intestinal Mucosa but Do Not Increase in
the Active Celiac Lesion”. ICMI 2009. Boston, USA. July 5-9, 2009.
Alexandre Corthay; Kristina Berg Lorvik; Peter O. Hofgaard and Bjarne Bogen: “Proteomics of macrophages involved
in successful cancer immunosurveillance”, World Immune Regulation Meeting II, Davos , Switzerland , March 22-25,
2009.
Elena Danilova , Espen S. Bækkevold, Ingebjørg Skrindo , Ludvig M Sollid, Frode L. Jahnsen, Finn-Eirik Johansen :
”In vitro expansion of resident T cells from the nasal mucosa”. 7th EAACI -GA²LEN Immunology Winter School ,
Davos , Switzerland , February 5-8, 2009.
Roberto Di Niro: “Visualization and isolation of cells producing anti-TG2 antibodies in the gut of CD patients”.
TRACKS Marie Curie workshop on Immunology and related techniques, August 24-26 2009, Tampere, Finland.
Alexander Erofeev; Dag Henrik Reikvam; Peter Gaustad; Krzysztof Grzyb; Anders Sandvik ;Frode L. Jahnsen;FinnEirik Johansen: ” Role of secretory antibodies and commensal microbiota in DSS-induced colitis” 14th International
Congress of Mucosal Immunology, Society for Mucosal Immunology, July 5-9 (2009), Boston, MA.
Tone Fredsvik Gregers: “Invariant chain and MIIC biogenesis” The 2nd European Congress of Immunology, September
13-16, 2009, Berlin, Germany.
Gunnveig Grødeland, Agnete Brusvik Fredriksen and Bjarne Bogen: “Targeted DNA vaccine protect mice against
H1N1 influenza” Harnessing Immunity to Prevent and Treat Disease, New York, USA, November 11-14, 2009.
Linda Haugen: “EGF activation induce a phosphorylation dependent alteration in Eps15 binding to endosomal
membranes.” Endocytic machineries in control of cell signalling and tissue morphogenesis, EMBO course, Chania,
Greece, 3 - 8 October, 2009.
38
Lene Støkken Høydahl: “Design of Recombinant Antibody-based Vaccines”. 2nd European Congress of Immunology,
Berlin, Germany, September 13-16 2009.
Ole Audun Werner Haabeth, Kristina Berg Lorvik, Bjarne Bogen, and Alexandre Corthay: “Cytokine profile of successful
cancer immunosurveillance mediated by tumor-specific CD4+ T cells”, Tri-Society Annual Conference, Cellular and
Cytokine Interactions in Health and Disease, Lisbon, Portugal, October 18-21, 2009.
Ole J. B. Landsverk: “Regulation of CD74 through dendritic cell maturation” The 2nd European Congress of
Immunology, September 13-16, 2009, Berlin, Germany.
Guro Reinholt Melum: “Characterization of resident APCs in steady-state human upper airway mucosa “ Phenotypical
Diversity of Macrophages & Dendritic Cells in Tissues and Organs, Regensburg 24-26 September 2009.
Luka Mesin: “Anti-TG2 B Cell immunity in coeliac disease”. TRACKS Marie Curie workshop on Immunology and
related techniques. August 24-26 2009, Tampere, Finland.
Cinzia Progida: “Rab7b is not a Rab7” Endocytic machineries in control of cell signalling and tissue morphogenesis,
EMBO course, Chania, Greece, 3 - 8 October, 2009.
Melinda Ráki: “Plasmacytoid dendritic cells are virtually absent from the celiac lesion”. 2
Immunology. Berlin, Germany. September 13-16, 2009.
nd
European Congress of
Sandvik, Anders ; Grzyb, Krzysztof; Reikvam, Dag Henrik; Erofeev, Alexander; Bækkevold, Espen S.; Jahnsen, Frode
L.; Johansen, Finn-Eirik: “Oral treatment with soluble beta-glucan protects against experimental ulcerative colitis”
14th International Congress of Mucosal Immunology, Society for Mucosal Immunology, July 5-9 (2009), Boston, MA.
Sandvik, Anders ; Bækkevold, Espen S.; Jahnsen, Frode L.; Johansen, Finn-Eirik: ” Effects of oral administration of
soluble β-glucan on the gut and gut-associated lymphoid tissue in mice” Innate, Adaptive and Regulatory Immune
Responses to Intestinal Microbiota, Keystone Symposia, January 13-18 2009, Taos NM.
Frode Skjeldal: “Early Endosomal fusion stimulates instantaneous tubular formationand fission” poster Endocytic
machineries in control of cell signalling and tissue morphogenesis, EMBO course, Chania, Greece, 3 - 8 October,
2009 .
Ingebjørg Skrindo: “Experimentally induced recruitment of Foxp3+ T cells in upper airway allergy” WIRM III, Davos,
Switzerland, March 23 2009.
Jorunn Stamnaes: “Gluten T-cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and
gluten ataxia”. 13th Int. Coeliac Disease Symposium. Amsterdam, the Netherlands. April 6-8, 2009.
Astrid E. V. Tutturen: “Specific enrichment of citrullinated peptides”. 3rd EuPA Congress. Stockholm, Sweden. June
14-17, 2009.
Inger Øynebråten, Agnete Brunsvik Fredriksen, Dan Barouch and Bjarne Bogen: “ Vaccibodies: a novel vaccine strategy
for HIV that target viral antigens to APC”, AIDS Vaccine Conference 2009, Paris, France, October 19-22, 2009.
39
Appendix 4
Press coverage
Vaccibody (Bjarne Bogen), ”En ny norsk vaksineoppfinnelse”, Genialt nr. 4, s 20-22, 2009, Forfattet av Ole Henrik
Brekke, CEO i Vaccibody AS
Bjarne Bogen, ”Verdens første matallergivaksine”, Aften, 3 siders oppslag inklusive førstsideoppslag, December 1th,
2009
Melinda Ráki, Knut EA Lundin and Ludvig Sollid, “Ny test gir raskt cøliaki-svar” VG, December 6th, 2009
Jan Terje Andersen and Inger Sandlie, ”Mindre medisin kan gi milliongevinst”, Uniforum October 8th, 2009
Tone F. Gregers, “Forskere blir holdt på gress”, Aftenposten, September 28th, 2009
Bjarne Bogen, ”En kur for alt”, Dagens Næringsliv (DNLørdag), 3 siders oppslag s. 56-59, inklusive forsideoppslag,
12/13 Sept,2009
Frode Jahnsen, “Interviewed about Asthma”, NRKP2 “Verdt å vite”, June 15th, 2009
Melinda Ráki, ”Cøliaki? Brød i tre dager kan gi svar”, Appollon 2/2009 p.12-13., June, 2009
Oddmund Bakke, ”Lysande immunceller i fire dimensjonar”, Appollon 2/2009 p.48-49., June, 2009
Bjarne Bogen and Ludvig Munthe, ”Studere sykdom hos lysende mus”, På hospitalet (magasin for Oslo
Universitetssykehus, rikshospitalet, Nr. 1 Juni 2009 s. 2. Oppslag.
Ludvig Munthe, ”Lysende mus varsler leddgikt”, Intervju med Ludvig Munthe, Lysende mus
NRK, Schrödingers katt, April 16th, 2009
Ludvig Sollid, Comment on “Gut reaction - Investigating coeliac disease”, Wellcome Trust, Wellcome News ‘58, April
7th, 2009
Bjarne Bogen, ”Kronikk: Veien mot en hiv-vaksine”, Dagsavisen, Tuesday Feb 3rd, 2009
Duodenal mucosa of coeliac patient after three days of gluten challenge. (Photo: Frode Jahnsen).
40
Appendix 5
Collaboration
National
Silke Appel, Broegelmann Res,. Lab., University of Bergen
Harm-Gerd Blaas, Dept of Gynecology and Obstretics, St. Olavs Hospital, Trondheim
Heidi Kiil Blomhoff, Institute of Biochemistry, University of Oslo, Oslo
Rune Blomhoff, Institute of Nutrition Research, University of Oslo, Oslo
Rolf Engstad, Biotec Pharmacon ASA, Tromsø
Terje Espevik, the Norwegian University of Science and Technology, Trondheim
Peter Gaustad, Institute of Medical Microbiolology, Rikshospitalet, Oslo
Tobias Gedde-Dahl, Department of Haematology, Rikshospitalet, Oslo
Einar Gran, Lovisenberg sykehus, Oslo
Harald Holte, the Norwegian Radium Hospital, Oslo
Jørgen Jahnsen, Department of Medicine, Aker sykehus, Oslo
Fridtjof Lund-Johansen, Institute of Immunology, Rikshospitalet, Oslo
Margaretha Johnsson, Dept. of Dermatology, St. Olavs Hospital, Trondheim, Norway
Terje E. Michaelsen, Norwegian Institute for Public Health, Oslo
Anne Spurkland, Institute of Basic Medical Sciences, University of Oslo
Harald Stenmark, the Norwegian Radium Hospital, Oslo
Elisabeth Søyland, the Norwegian Medical Association
Geir Tjønnfjord, Department of Haematology, Rikshospitalet, Oslo
International
Ablynx N.V., Zwijnaarde, Belgium.
Daniel Aeschlimann, University of Wales, Cardiff, UK
Dan Barouch, Harvard University, MA, USA
Francisco Barro, Instituto de Agricultura Sostenible, Cordoba, Spain
Richard S. Blumberg, Harvard Medical School, MA, USA
Harald von Boehmer, Harvard University, MA, USA
Kurt Bommert, University of Würzburg, Germany
Cecilia Bucci, University of Salento, Lecce, Italy
Søren Buus, University of Copenhagen, Denmark
Niklas Dahl, Uppsala University, Sweden
Riccardo Dolcetti, CRO - National Cancer Institute, Aviano, Italy
Morten Dziegiel, Rigshospitalet - Copenhagen University Hospital, Denmark
Peter M Elias, University of California San Francisco, CA, USA
Laszlo Fesus, University of Debrecen, Hungary
Georg Georgiou, Department of Biomedical Engineering, University of Texas, Austin, USA
41
Carmen Gianfrani, Institute of Food Sciences, Avellino, Italy
Sven Hammerschmidt, Ludwig-Maximilians University, Munich, Germany
Ingrid Hausser, Department of Dermatology, University Hospital Heidelberg, Germany
Valerie Hohman, University of San Diego, CA, USA
David W. Holden, Imperial College London, London, England
Patrick Holt, Telethon Institute of Child Health Research, Perth, Australia
Bertrand Huard, University of Geneva, Switzerland
Bana Jabri, University of Chicago, IL, USA
Charlotte S. Kaetzel, University of Kentucky, KY, USA
Chaitan Khosla, Stanford University, CA, USA
Chu-Young Kim, National University of Singapore, Singapore
Frits Koning, Leiden University Medical Center, the Netherlands
Ilma Korponay-Szabo, Heim Pal Children’s Hospital and University of Debrecen, Budapest,
Hungary
Wayne Lencer, Harvard Medical School, MA, USA
Markku Mäki, University of Tampere, Finland
Kristiina Malmstrøm, Helsinki University, Finland
Roberto Marzari, University of Trieste, Italy
Elizabeth D. Mellins, Stanford University, CA, USA
Jeffery Miner, Renal Division, Dept. of Internal Medicine, Washington University School of
Medicine, St. Louis, Missouri.
Åsa Torinsson Naluai, Sahlgrenska Academy, Gothenburg University, Sweden
Claus Munck Petersen, Århus University, Denmark
Richard Pleass, University of Nottingham, UK
Klaus Rajewsky, Harvard University, MA, USA
Paul Roche, NIH, Bethesda, USA
Päivi Saavalainen, University of Helsinki, Finland
Janneke Samson, Erasmus University Medical Center, Rotterdam, the Nederlands
Daniele Sblattero, University of Piemonte, Italy,
Mark Shlomchik, Yale University, CT, USA
Richard Strugnell, University of Melbourne, Australia
Gestur Vidarsson, Department of Experimental Immunohematology, Sanquin Research,
University of Amsterdam
Reinhard Voll, University of Erlangen-Nürnberg, Germany
Patrick Wilson , University of Chicago, IL, USA
Hideo Yagita, Jutendo University, Japan
Dov Zipori, Weizmann Institute, Israel
42
Appendix 6
Funding
Personnel funding per Dec 31st 2009
20
20
17
15
13
10
10
10
4
5
1
1
2
1
3
2
1
2
1
1
1
0
H
S
sA
ie
od
O
BI
EM
H
ib
cc
Va
UU
O-
Ui
R
O/
Ui
O
Ui
E
UG
-F
te
itu
on
ac
m
ar
st
In
CN
/R
RH
RH
N
RC
N
RC
S
NC
RF
E
RS
JD
H
R
H&
d
Ph
CN
/R
EU
EU
oa
Br
ec
ot
Bi
EU - European Union
National
H&R - Norwegian Foundation for Health and
Rehabilitation
HRSE - Health Region South East
University of Oslo
JDRF - Juvenile Diabetes Research Foundation
Oslo University Hospital Rikshospitalet
NCS - Norwegian Cancer Society
Oslo University Hospital Ullevål
RCN - Research Council of Norway
Norwegian Foundation for Health and Rehabilitation
RCN-FUGE - Funksjonell genomforskning (RCN)
Health Region South East
RH - Rikshospitalet University Hospital
Norwegian Cancer Society
UiO - University of Oslo
Research Council of Norway
UiO-EMBIO - Steering board for Molecular Life
Sciences (UiO)
Vaccibodies AS
UUH - Ullevål University Hospital
International
Broad Institute
European Union (TRACKS MRTN-CT_2006-036032, PreventCD
FOOD-CT-2006-36383, Vital FP6-LIFESCIHEALTH-037874)
Juvenile Diabetes Research Foundation
Multiple Myeloma Research foundation
Novozymes Biopharma DK A/S
Research Council of Belgium
43
Ce
ion
IR
n tr
e fo
lat
r Immune Regu
Centre for
Immune Regulation
Rikshospitalet, Building A2/A3
Sognsvannsveien 20
0027 OSLO
design | easy.no
Phone: +47 23 07 35 00
Fax: +47 23 07 35 10
Email: [email protected]
www.cir.uio.no

CIR Annual Report for 2009

Transcription

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