Annual Review 2009-2010

Comments

Transcription

Annual Review 2009-2010
LUNDBECKFONDEN
THE LUNDBECK FOUNDATION 2009│10
MELIE CAMMILLA ANDERSEN┃PROFESSOR PH.D. JENS SKORSTENGAARD ANDERSEN┃KLINISK ASSIST
LDURSDOTTIR┃PROFESSOR DR.MED. PER BECH┃STUD.SCIENT. BIRGITTE BERTELSEN┃VIDENSKABE
PH.D. CORD BRAKEBUSCH┃LEKTOR PH.D. SUSANNE BRIX PEDERSEN┃PROFESSOR DR.PHARM. HANS
GE CHRISTINA CHRISTOFFERSEN┃PH.D.-STUDERENDE CAND.POLYT. ANETTA CLAUSSEN┃LEKTOR PH
FFEL DINANT┃PROFESSOR DR.MED. HENRIK JØRN DITZEL┃LEKTOR LIC.SCIENT. MICHAEL ROHR DRE
PH.D. CHRISTER STENBY EJSING┃LEKTOR PH.D. LARS ELLGAARD┃FORSKNINGSLEDER PH.D. LARS H
RASMUSSEN┃ASSISTANT PROFESSOR PH.D. ROBERT ANDREW FENTON┃POST DOC. PH.D. AASA FER
NDERS FUGLSANG-FREDERIKSEN┃PH.D.-STUDERENDE CAND.MED. JASNA FURTULA┃LÆGE ELISABE
. CLAUS HØJBJERG GRAVHOLT┃PROFESSOR DR.MED. NIELS GREGERSEN┃LEKTOR PH.D. MICHAEL J
ESSOR TEKN.DR. VIKTORIA HANCOCK┃PROFESSOR DR.SCIENT. STEEN HANNESTAD┃AFDELINGSLÆG
N┃PH.D.-STUDERENDE CAND.SCIENT. SIMON HAUERSLEV┃POST DOC. PH.D. JAKOB HULL HAVGAARD
SCIENT. PHILIP HOFMANN┃PH.D.-STUDERENDE CAND.SCIENT. MARLENE VIND HOFMEISTER┃POST DO
COB PADE RAMSØE JACOBSEN┃LÆGE PH.D. LINDA JAKOBSEN┃VIDENSKABELIG ASSISTENT CAND.S
A. JENSEN┃PH.D.-STUDERENDE CAND.SCIENT. SØREN SKOV JENSEN┃PROFESSOR DR.MED. THOMAS
ENDE CAND.SCIENT. MATHIAS JUL JØRGENSEN┃LEKTOR PH.D. THOMAS J.D. JØRGENSEN┃LEKTOR P
AGNETE KIRKEBY┃SCHOLARSTIPENDIAT ANNA MATHIA KLAWONN┃AFDELINGSLÆGE SENIORFORSKE
EGAARD LARSEN┃POST DOC. PH.D. MAGDALENA JANINA LASKA┃POST DOC. PH.D. JENS PETER HOL
DR.MED. YAWEI LIU┃ASSOCIATE PROFESSOR PH.D. ROSA LAURA LÓPEZ MARQUÉS┃POST DOC. PH.D
DERENDE CAND.SCIENT. OLE AALUND MANDRUP┃LEKTOR PH.D. VLADIMIR MATCHKOV┃PROFESSOR
POST DOC. PH.D. NINELL POLLAS MORTENSEN┃ADJUNKT PH.D. JENS PREBEN MORTH┃POST DOC. P
NNE NIELSEN┃PH.D.-STUDERENDE CAND.SCIENT. JOACHIM NIELSEN┃PROFESSOR PH.D. JOHN NIELS
PH.D.-STUDERENDE CAND.SCIENT. RIE NYGAARD┃POST DOC. PH.D. RIKKE NØRREGAARD┃DIREKTØR
RESEARCHER PH.D. BOB ORANJE┃BIOKEMIKER PH.D. CARLO GUNNAR OSSUM┃POST DOC. PH.D. SY
S STEEN PEDERSEN┃LEKTOR PH.D. STEEN PEDERSEN┃MOLEKYLÆRBIOLOG PH.D. TANJA XENIA PED
UGDAHL┃PROJEKTLEDER CAND.SCIENT. THOMAS RASMUSSEN┃POST DOC. PH.D. MARTIN FREDENSB
ARSEN┃FYSIKER PH.D. MADS T. FRANDSEN┃POST DOC. JUNIOR GROUP LEADER CAMILLA SCHEELE
K FORSKNINGSLEKTOR DR.MED. LISELOTTE SKOV┃POST DOC. CAND.SCIENT. GUSTAVO STADTHAGE
T. PER SVENNINGSEN┃STUD.MED. ASGER SVERRILD┃POST DOC. PH.D. RIKKE SØGAARD┃POST DOC
ØRRING┃POST DOC. CAND.SCIENT. WIMAL UBHAYASEKERA┃VIDENSKABELIG MEDARBEJDER CAND.
ARD┃PROFESSOR PH.D. PETER VUUST┃PROFESSOR DR.MED. GUNHILD WALDEMAR┃VIDENSKABELI
DBY┃LEKTOR PH.D. DANIEL WÜSTNER┃LEKTOR CAND.SCIENT. KIRSTEN WØLDIKE┃PH.D.-STUDEREN
ERENDE CAND.POLYT. MORTEN ALHEDE┃LEKTOR PH.D. TINE ALKJÆR ERIKSEN┃VIDENSKABELIG ASS
USANA AZNAR KLEIJN┃LÆGE PH.D. IBEN BACHE┃LEKTOR PH.D. LASSE KRISTOFFER BAK┃ADJUNKT
DERENDE MADS TVILLINGGAARD BONDE┃ADJUNKT PH.D. CHARLOTTE MENNÉ BONEFELD┃POST DOC
ØREN BUUS┃LEKTOR PH.D. LI CHEN┃ADJUNKT CAND.SCIENT. MARCO CHIARANDINI┃ADJUNKT PH.D.
E CAND.SCIENT. THOMAS DALSGAARD┃CAND.SCIENT. BRIAN DELLA VALLE┃PH.D.-STUDERENDE CAN
TER EDUARD┃POST DOC. PH.D. KRISTOFFER LIHME EGEROD┃POST DOC. CAND.SCIENT. VERA EHRE
ARSTEN FABER┃VIDENSKABELIG ASSISTENT PH.D. HELENE FAUSTRUP┃PH.D.- STUDERENDE CAND.S
ERG┃POST DOC. PH.D. AGLA JAEL RUBNER FRIDRIKSDOTTIR┃PH.D. CAND.SCIENT. MADS T. FRANDSE
ER CAND.SCIENT. GEORGE GEGELASHVILI┃PROFESSOR DR.MED. ULRIK GETHER┃LEKTOR DR.PHIL. M
SIG FAARUP RASMUSSEN┃AFDELINGSLÆGE DR.MED. JENS PETER GØTZE┃RESEARCH SCHOLAR CA
H.D. LARS HESTBJERG HANSEN┃LÆGE PH.D. TINE WILLUM HANSEN┃RESEARCH ASSISTANT PH.D. LI
. PH.D. PETER FØNSS HERSKIND┃LEKTOR PH.D. ASGER HOBOLTH┃PROFESSOR PH.D. ELSE KAY HOF
HVID┃PH.D.-STUDERENDE CAND.SCIENT. SARA MAJ WÄTJEN HYLDIG┃LEKTOR PH.D. ALBERTO IMPAR
DR.MED. KIMMO JENSEN┃PROFESSOR DR.SCIENT. MOGENS HØGH JENSEN┃KLINISK ASSISTENT CAN
RUD JORDAN┃STUD.SCIENT. FREDERIK CUNDIN JØLVING┃LEKTOR DR.MED. ARNE LUND JØRGENSEN
THE LUNDBECK FOUNDATION 2009│10
Board of Trustees
Jes Østergaard, Director, Civil
Engineer
Thorleif Krarup, Director, B.Sc.
(econ), B.Com.
Jeanette Larsen, Laboratory
Specialist, employee representative
BOARD OF TRUSTEES AND MANAGEMENT
Niels Johansen, Research
Director, Civil Engineer, employee
representative
Mikael Rørth, Professor, Chief
Physician, M.D.
Steen Hemmingsen
Management
Nils Axelsen, Vice-Chairman,
Chief Physician, M.D.
Mogens Bundgaard-Nielsen,
Chairman of the Board, Director,
Civil Engineer, B. Com.
Anne-Marie Engel
Management
Steen Hemmingsen, Managing
Director, Ph.D.
Grants
Administration/secretariat
Britt Wilder, Executive Secretary
Bertil From
Research
Anne-Marie Engel, Director of
Research, Ph.D.
Ulla Jakobsen, Science Manager
Kirsten Ljungdahl, Secretary
Finance and Investment
Bertil From, Chief Financial Officer
Portfolio investments
Peter Sehested, Senior Investment
Manager
Susanne Bernth, Senior Controller
Peter Adler Würtzen, Research
Scientist, Ph.D. employee
representative
Jørgen Huno Rasmussen, Group
CEO, Civil Engineer
Mette Kirstine Agger
LFI Life Science Investments
Mette Kirstine Agger, Executive
Director, Head of LFI Life Science
Investments
Johan Kördel, Senior Investment
Director
Casper Breum, Investment Director
Accounting/Controlling
Claus Køhler Carlsson, Director,
Accounting & Tax
Vibeke Bache, Head of Accounts
Danielle Bernth, B.Sc.
THE LUNDBECK FOUNDATION
The Lundbeck Foundation is a commercial foundation established in 1954. Its main objective is to maintain and expand the activities
of the Lundbeck Group and to provide funding for scientific research of the highest quality.
100%
LFI a/s
Investment & holding company
LISTED
SUBSIDIARIES
70%
H. LUNDBECK A/S
OTHER
INVESTMENTS
38%
ALK ABELLÓ A/S
(66%.OF THE VOTES)
LFI LIFE SCIENCE
INVESTMENTS
50%
OBEL-LFI
EJENDOMME A/S
PORTFOLIO
contents
THE LUNDBECK FOUNDATION'S ACTIVITIES IN 2009
2
GRANTS IN 2009
5
GRANT-MAKING POLICY
10
THE FIRST GENOME FROM A PREHISTORIC HUMAN
12
NANOMEDICINE – AN INTRODUCTION
17
CENTRES OF EXCELLENCE 2009 – NANOMEDICINE
20
THE LUNDBECK FOUNDATION'S RESEARCH PRIZES
26
THE LUNDBECK FOUNDATION'S JUNIOR GROUP LEADER FELLOWSHIPS
34
LFI a/s – THE LUNDBECK FOUNDATION'S COMMERCIAL ACTIVITIES
41
THE LUNDBECK FOUNDATION'S MANAGEMENT AND CORPORATE GOVERNANCE
43
RESULTS 2009
44
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S ACTIVITIES IN 2009
2009 in brief
The Lundbeck Foundation donated DKK 340 million to research
in the biomedical and natural sciences in 2009, funding some 500
researchers at Danish universities and, increasingly, Danish
researchers at universities abroad. Despite the financial crisis in
2008 and early 2009, a combination of the scale of its financial
resources and its long-term outlook have enabled the Foundation
to stick to its strategy of not allowing the return on investment
in any particular year to have a negative impact on its funding
activities. Funding will also continue in 2010 at around the level
of 2009.
The Ministry of Science devised a Research Barometer in 2009.
It shows, for example, that Danish research is ranked very highly
internationally in terms of the number of publications and citations from them. However, it seems to be increasingly difficult
to translate basic research into new products. Ownership of the
pharmaceutical companies H. Lundbeck A/S and ALK-Abelló A/S
and support for university research mean that the Foundation is
involved in the whole chain, from basic research through applied
research and development to production and marketing. In
addition to the researchers funded by the Foundation at universities and university hospitals, the two companies mentioned above
employ approx. 1,800 people and spent a total of approx. DKK
3.5 billion p.a. on research and development.
The basic research conducted at universities has to be qualified by
broader criteria than just new products that reach the market in a
short time-scale, of course, but it is also important that opportunities are created to exploit the business potential that emerges from
university research. In 2009, the Lundbeck Foundation set up a
special investment entity, primarily for life-science companies, in
Denmark and abroad. As part of this strategic enhancement, the
Foundation's investment and holding company, LFI a/s, has
assumed responsibility for a number of biotech investments
previously under the auspices of H. Lundbeck A/S, concentrating
the Group's resources in the life-science sector in the new investment entity LFI Life Science Investments.
The Ministry of Science's Research Barometer reveals that 2.5%
of research funding at the universities is donated directly by
business, a comparatively low figure in international terms. However, Danish foundations, including the Lundbeck Foundation and
the Novo Nordisk Foundation, together fund almost 10% of total
Danish university research, a comparatively high figure that puts
the business community's contribution to university research in a
more balanced perspective. Much of the Lundbeck Foundation's
revenue stems from dividends from the companies in which it is
the majority shareholder. A proportion of these profits is channelled into university research, and thereby also to the education of
the graduates that the business and the health sector need.
Financially, 2009 was a good year for the Foundation. It made
a profit of DKK 2,639 million, of which DKK 1,505 million
consists of return on investment, and DKK 1,169 million
represents a share of the operating profit from Group companies.
The fair value of the Foundation's liquid funds, i.e. investments
not related to H. Lundbeck A/S and ALK-Abelló A/S, increased
from DKK 10,834 million at the end of 2008 to DKK 12,091
million. In other words, the investment loss suffered in 2008 has
now been recouped. The return on investment was 14.3%. At the
end of 2009, equity was DKK 18,324 million. Measured at market
prices this corresponds to a value of DKK 26,138 million.
Most of the Foundation's grants go to what is referred to as
unrestricted research, i.e. the grants are awarded solely on the basis
of the quality, rather than the subject, of the research. These are
known as bottom-up grants. In 2009 as in previous years, topdown or strategic grants have been allocated to research centres in
areas defined by the Foundation Board. The theme in 2009 was
nanomedicine. This theme was selected following consultation
with the Foundation's advisors in Denmark and abroad. DKK 100
million was donated to the three successful applications to emerge
from the tendering process. The nanomedicine theme and each of
the three centres of excellence are described in detail elsewhere in
this publication.
These three centre grants bring the total number of research
centres launched by the Foundation in the last five years to 15 and
the number of researchers therein to 300. As a private body, it is
important that the Foundation continually evaluates where it can
make a difference compared to the initiatives taken by the public
research councils, the universities and other private foundations.
As a private body, the speed of the decision-making process enables
the Board to adapt the Foundation’s activities to trends it considers
significant. The importance of the work of the private foundations
is illustrated by this quote from Professor Eske Willerslev, whose
ground-breaking project was funded by the Lundbeck Foundation
in 2009: "without these private donations, Denmark would never
At the award ceremony of the Lundbeck Foundation's Talent Prizes are the recipients (seated from left) Ph.D. Mads Toudal Frandsen, Ph.D. Kamilla Miskowiak, Ph.D. Emil
Loldrup Fosbøl and Managing Director Steen Hemmingsen, Chairman of the Board of Trustees Mogens Bundgaard-Nielsen and Chairman of the Foundation's Research
Prize Committee, Nils Axelsen.
have won the race to sequence the first genome from an extinct
type of human – a breakthrough that puts Denmark on the world
map”……..” Scientific breakthroughs often don't just depend
upon the amount of money, but also on how quickly the cash is
activated. Top international leading research groups are engaged in
fierce competition, so it's only weeks or months that separate winners from losers – and there is only one winner, i.e. the team that
gets there first. The Lundbeck Foundation realises this, and for this
reason alone plays an absolutely crucial role in Danish basic research” (see article elsewhere in the publication).
In recent years, the Foundation has noted the establishment of a
wide range of research centres that involve both public and private
funders, including newer, private stakeholders. At present, the need
for the Lundbeck Foundation to make new investments in research
centres is therefore considered to be less pronounced.
The Board has therefore decided that the Foundation would exert a
more positive influence on Danish research by prioritising the funding of smaller new groups headed by outstanding young researchers - from Denmark or abroad - who will be responsible for their
own choice of research area at a Danish institution. The Foundation's total allocations budget for 2010 (approx. DKK 340 million)
is therefore allocated to bottom-up research in biomedical and
natural sciences, including neuroscience in a broad sense without
subject limitation. This is unrestricted research, and the crucial
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S ACTIVITIES IN 2009
factor is the combination of the cutting-edge nature of the project
and the researchers’ qualifications. Examples from Nobel Prizewinners among others indicate that researchers in the age 35-40 are
often particularly original and productive. It is also recognised that
the traditional funding system fails to accord sufficient significance
to providing outstanding researchers in this age group with the
optimal working conditions that will enable them to compete
with research institutions abroad. It is here that the Foundation
expects to be able to make a difference. For 2010, it has earmarked
a total of DKK 100 million for seven fellowships for outstanding
young research leaders, from Denmark or abroad, who wish to
start their own research group at a Danish institution. Of the
seven fellowships, two worth DKK 25 million (€ 3 million) each
will be advertised as Grants of Excellence within the neuroscience
area for two researchers who already have a proven track record of
international research and research management. Furthermore, five
Junior Group Leader Fellowships of DKK 10 million each will be
awarded to young researchers from Denmark or abroad, typically
in their early-to-mid 30s, who also want to start their own research
group at a Danish institution. Again, these fellowships will be
awarded following open competition, international advertisement,
and assessment by external experts.
cial activities. At the end of 2009, a property investment company
was also established as a joint venture with C.W. Obel Ejendomme
A/S, namely Obel-LFI Ejendomme A/S which is managed by C.W.
Obel Ejendomme A/S. At the end of 2009, the Foundation and
LFI a/s employed 14 people, up from 10 at the end of 2008. A
new scientific advisory committee has been set up to process
applications for research grants for natural science projects. The
advisory committee for the biomedical sciences continues as before.
All grant applications are now put before an advisory committee
with a majority of external members. Ad hoc committees are set up
to process applications for centres and fellowships. A list of members of the two advisory committees is available on page eight and
nine of this publication and at the Foundation's website, summary
of all donations made up to and including 2009. The site also
functions as a portal to the Foundation's online application system.
This publication contains details of the grants allocated in 2009,
articles by and about the five recipients of the Junior Group Leader
Fellowships, the recipients of research prizes and the new research
centres, as well as an article about the Foundation's business
activities carried out in the wholly owned investment and holding
company LFI a/s.
Mogens Bundgaard-Nielsen
Chairman of the Board of
Trustees
The Board remained unchanged in 2009. The Civil Affairs Agency
approved an amendment to the Board's statutes so that all chartered members now have to stand for re-election every year and the
maximum term for each member is 12 years. Every effort will
continue to be made to ensure that the six chartered members
elected by the Board represent different areas of scientific, financial
and business expertise. This serves the best interests of the Foundation's funding activities as well as its commercial activity in LFI
a/s, whose board consists of the same members as the Board of the
Foundation.
The Foundation and LFI a/s increased its scope of investment
activities in 2009 with the addition of LFI Life Science Investments under LFI a/s. Additional resources were added to the finan-
The Lundbeck Foundation would like to thank its employees,
managers of subsidiaries and partners on scientific advisory
committees, universities and official bodies for their positive input
in 2009.
Steen Hemmingsen
Managing Director
grants 2009
In 2009, the Lundbeck Foundation allocated a total of DKK 340
million in research grants. Based on academic evaluations by
assessment panels and ad hoc review committees with a majority
of external assessors, the Board has approved DKK 295 million
in grants to basic research, DKK 37 million to clinical/applied
research and DKK 8 million to other forms of research.
The three centres are:
NanoCAN – The Lundbeck Foundation Nanomedicine
Research Centre for Cancer Stem Cell Targeting Therapeutics,
headed by Professor Jan Mollenhauer, Department of Molecular Medicine, University of Southern Denmark. The Centre
received a grant of DKK 35 million.
research centres
In 2008, the Lundbeck Foundation hosted an inspiration seminar,
at which Danish universities and university hospitals were invited
to propose fields of study in which they believed that Danish
research was of a high international standard and had the potential
to further strengthen its position. Based on the proposals submitted, some of which were presented at the seminar, the Board
decided, in consultation with an international panel, that the 2009
theme for the Lundbeck Foundation's research grants should be
nanomedicine.
After consideration and recommendation by an international panel
with expertise in both nanomedicine and nanotechnology, a total
of DKK 100 million was donated to three Centres of Excellence.
The centre’s research focuses on the targeted treatment of
cancer stem cells via nano-carriers.
In the same way that the body's ordinary stem cells are responsible
for maintaining normal tissue, the so-called cancer stem cells seem
to give rise to tumours. Cancer stem cells are suspected of being
resistant to radiation and chemotherapy, and of helping to spread
cancer cells. This means that new ways of treating cancer must be
found. NanoCAN's goal is to develop new nano-medicines that
kill cancer stem cells without causing harm to normal stem cells.
One of the key activities at NanoCAN will be to devise new drugs
by studying each of the 20,000 human genes – this will be done
using advanced robots that function as a miniature assembly line.
NanoCAN's strategy is to combine nano-medicines on the basis
the grants awarded in 2009 can be broken down as follows:
The Foundation’s funding strategy and grants can be viewed on the Foundation’s website:
www.lundbeckfonden.dk
    
 
 
( )
3 Centres of Exellence
Prizes
Fellowships
Projects
Total (DKK million)
100
1
50
144
295
2
35
37
Number of project grants
Average per project grant
180
0.8
63
0.6


8
8
100
3
50
187
340
22
0.4
265
-
THE LUNDBECK FOUNDATION 2009│10
GRANTS IN 2009
The beneficiary of the Foundation's Prize for Young Researchers 2009, Professor Niels Mailand in conversation with the Chairman of the Foundation's Research Prize
Commitee Nils Axelsen and the Chairman of the Board of Trustees Mogens Bundgaard-Nielsen (right).
of various biological building blocks made up of lipids and RNAs
that either contain a medicine or which can locate and possibly kill
a cancer cell.
The Lundbeck Foundation's NanoCAN Centre will initially
focus on breast cancer, the leading global cause of cancer deaths in
women.
CBN – The Lundbeck Foundation Centre for Biomembranes
in Nanomedicine headed by Professor Ulrik Gether, Department of Neuroscience and Pharmacology and Associate
Professor Dimitrios Stamou, Department of Neuroscience
and Pharmacology & Nano-Science Centre, both of the
University of Copenhagen. The centre received a grant of
DKK 34 million.
Communication between nerve cells and signaling between
bacteria.
The centre will study the basic biological processes in the cell's
outer barrier, the cell membrane, which forms the basis for the
cells' ability to communicate with each other via chemical signals.
Surprisingly, the membrane processes exhibit many features
common to both bacteria and human cells, which underlines their
fundamental importance to all living organisms. Disruption of the
chemical signals between cells is a key element in the development
of diseases in the brain. Chemical signaling between bacteria is
presumed to play a crucial role in their ability, in some cases, to
bypass the body's immune system.
The centre will use a whole range of new nanoscale technologies
to study membrane processes all the way down to single-molecule
level. In the long term, the results may not only lead to new treatments for brain diseases and new ways of combating bacterial
infections, but may also lead to the development of new biological
nanosensors for use in the diagnosis and design of nanoscale
medicine capsules for targeted treatment of specific cell types.
LUNA – The Lundbeck Foundation Nanomedicine Centre
for Individualized Management of Tissue Damage and Regeneration, headed by Professor Allan Flyvbjerg, Aarhus University
Hospital and Faculty of Health Sciences, Aarhus University
and Professor Jørgen Kjems, Interdisciplinary Nanoscience
Center, Aarhus University. The centre received a grant of
DKK 30 million.
The mechanisms behind the imbalance between tissue damage
and tissue repair, caused by disease.
The centre's core hypothesis is that cardiovascular diseases and
musculoskeletal disorders are caused by an imbalance between
disease-induced tissue damage and the body's natural ability to
repair or rebuild damaged tissues. The projects are designed to
illustrate the key mechanisms that cause disease, and to develop
techniques to restore this balance and stimulate tissue repair.
The centre will focus on a newly discovered group of recognition
molecules that are expected to rectify the imbalance between
tissue damage and tissue repair, as well as explain differences in
the development of these diseases between different individuals.
Studies of these molecules and the way they work will be conducted using new techniques from the nano world. The project
will develop nano-based techniques for developing new 'molecular'
medicine, new disease-imaging methods, tissue-specific administration of medication and new technologies for tissue protection and
reconstruction.
junior group leader fellowships
In 2009, the Lundbeck Foundation awarded five Junior Group
Leader Fellowships for young researchers who conducted outstanding research and are now qualified to set up their own research
groups. Three fellowships were awarded to life-science researchers,
and two to natural-science researchers.
In 2010, in accordance with the Foundation's decision to focus
on research management and future managers, five Junior Group
Leader Fellowships will also be awarded to researchers from
Denmark and abroad who wish to establish their research with
a group at a Danish university or university hospital.
The Fellowship recipients in 2009 were:
Post doc. Søren Gøgsig Faarup Rasmussen, Ph.D.,
the University of Copenhagen, Department of Neuroscience and
Pharmacology. Søren Gøgsig Faarup Rasmussen comes to the
University of Copenhagen after completing his post-doctorate at
Stanford University. His new group's research will focus on understanding the three-dimensional structure of different types of cellmembrane proteins (proteins that are integrated into the surface
of the body's cells) and how they change shape and structure as a
result of their function.
The title of the project is: Structural and functional studies of
monoamine neurotransmitter activated G-protein-coupled receptors and monoamine transporters
Associate Professor Steen Brøndsted Nielsen, Ph.D.,
Department of Physics and Astronomy, Aarhus University. Steen
Brøndsted Nielsen will continue as associate professor at Aarhus
University, and will lead a group that focuses on research into and
description of excited molecular states, their appearance, dynamics
and influence on reaction paths. One objective of this work is to
understand DNA molecules' reactions to light. At the same time,
work will be done to investigate DNA's properties as 'nanowires',
for use in the molecular electronics of the future.
The title of the project is: Excited state physics of bare and solvated
molecular ions
Neuroscience
Cell & Molecular Biology
Physiology + pharmacy
Cancer research
Microbiology + immunology
Biochemistry
Genetics + other basic
biomedical research
Total

 
 .
39
29
16
4
18
2
47
17
9
3
10
1
17
9
125
The title of the project is: Functional characterization of depolarization-dependent signaling pathways in nerve terminals.
Assistant Professor Lene Niemann Nejsum, Ph.D.,
Department of Molecular Biology, Aarhus University. Lene
Niemann Nejsum returns to Denmark following a post doc. stay
P    , 
 ( )   
    ,
 

Associate Professor Martin Røssel Larsen, Ph.D.,
University of Southern Denmark, Department of Biochemistry
and Molecular Biology. His group will focus on examining the
underlying mechanisms in the molecular signaling inside nerve
cells, which serves to maintain the communication between nerve
cells that is essential for a functioning nervous system. Martin
Røssel Larsen previously had a prolonged research stay in Australia,
where he established a fruitful collaboration with a group that will
play a part in his fellowship project.
96

  .
 
Neurology, neurosurgery, psychiatry
and physiology
Clinical pharmacology, genetics
and microbiology
Hepatology, endocrinology, nephrology
and gastroenterology
Cardiology
Gynaecology, ophthalmology, obstetrics,
surgery, anaesthesiology and paediatrics
Oncology + haematology
General medicine, infection medicine
and lung diseases
Internal medicine, public-health medicine,
geriatrics and more
Total
14
11
8
2
6
5
6
1
7
4
3
3
4
2
13
5
61
33
THE LUNDBECK FOUNDATION 2009│10
GRANTS IN 2009
the lundbeck foundation’s
international scientific advisory committees
Mikael Rørth, Chairman,
Professor, Chief
Physician, M.D. Member
of the Foundation’s
Board of Trustees
Ole Petter Ottersen,
Professor, M.D.
Institute of Basic Medical
Sciences, Centre for
Molecular Biology and
Neuroscience, Oslo
University, Norway
Ole William Petersen,
Professor, M.D.
Institute for Cellular and
Molecular Medicine,
Copenhagen University,
Denmark.
Bertil Hamberger,
Professor, M.D.,
Department of Surgery,
Karolinska Hospital
Solna, Stockholm,
Sweden
Edvard Smith,
Professor M.D.,
Clinical Research Center,
Karolinska Institutet,
Stockholm, Sweden
Jørgen Frøkiær,
Professor, M.D
Department of Clinical
Physiology and Nuclear
Medicine, Aarhus University Hospital, Skejby
Denmark
Anders Bjørklund,
Professor, M.D., Ph.D.
Department of Physiological Sciences, Wallenberg Neuroscience
Centre, Lund University,
Sweden.
Nils Axelsen,
Chief Psysician, M.D.
Vice-Chairman of the
Foundation's Board of
Trustees
at Stanford University in the USA. Her research there led to the
description of an important directional-sorting mechanism for
membrane proteins in epithelial tissues. Her group in Denmark
will continue work on mapping and describing this mechanism.
Research Prizes
Since 1987, the Lundbeck Foundation has awarded research prizes
in recognition of excellent research and/or particularly promising
young researcher profiles.
The title of the project is: Regulation of post-Golgi sorting and
trafficking in polarized epithelial cells
The Lundbeck Foundation Nordic Research Prize of DKK 2
million was awarded to Professor Jes Olesen, Danish Headache
Centre, Glostrup Hospital. He received DKK 600,000 as a personal honorary award and DKK 1,400,000 for research of his choice.
Associate Professor Troels C. Petersen, Ph.D.
the Niels Bohr Institute, University of Copenhagen. Troels C.
Petersen is establishing himself with a research group at the Niels
Bohr Institute. He has studied particle physics at several research
institutions, most recently at the Large Hadron Collider at CERN,
which remains the basis for the experimental part of his research.
His group will focus on the description of the 'dark matter' that
constitutes a large proportion of our universe, and about whose
properties we currently know very little.
The title of the project is: Searching for dark matter at Cern’s LHC
accelerator
Project funding
The majority of the Foundation's project funding is allocated to
biomedical research. In 2009, the Foundation received a total of
1,055 applications for project funding. Of these, 778 concerned
biomedicine and 229 natural sciences. Grants were approved for a
total of 265 projects, 180 of which were basic research projects.
The tables show how project funding in biomedical science is
divided between basic and clinical/ applied research, and how the
grants are divided between subject groups in terms of number and
amounts.
In natural science, a total of DKK 35 million was awarded to 62
projects (52 basic research and 10 applied research and development).
Jes Olesen founded the Danish Headache Centre at Glostrup
Hospital, a national research- and treatment centre for particularly
severe cases of migraine and other headaches. For over three decades, he has led a headache-research group that has made several
groundbreaking discoveries with great international impact. Jes
Olesen's detailed description and classification of the different
types of migraine has also led to the establishment, under his initiative, of a set of internationally accepted standards for defining and
classifying over 100 different types of headache. This has helped
to strengthen international collaborative research on migraines as
research findings in one country can now be transferred directly to
other countries. The prize was handed over at a ceremony in
Glostrup Hospital in March 2010.
The Foundation's Research Prize for Young Scientists under 40 was
in 2009 awarded to Professor Niels Mailand, Group Leader in the
Department of Disease Biology, Novo Nordisk Foundation Centre
for Protein Research, University of Copenhagen. He was awarded
the prize in recognition of his outstanding contribution to the understanding of the DNA damage response – a cellular surveillance
system that protects against mutations and major genetic damage,
and which, for normal cells, serves as a primary defence against
the development of serious diseases such as cancer. Niels Mailand
describes his research in detail in an article in this publication.
Jes Østergaard,
Chairman, Director, Civil
Engineer. Member of the
Foundation’s Board of
Trustees
Björn Lindman,
Professor, Ph.D., Dept.
of Chemistry & Chemical
Engineering, Lund
University, Sweden
Knut Conradsen,
Professor, Dr.Scient.,
The Technical University
of Denmark
Torkild Andersen,
Professor, Dr. Phil.,
Aarhus University
Talent Prizes
The Lundbeck Foundation awarded prizes to three talented
researchers under 30 who have conducted particularly promising
research in biomedical and natural sciences. The 2009 awards,
which consist of personal prizes of DKK 100,000, went to Kamilla
Miskowiak, Emil Loldrup Fosbøl and Mads Toudal Frandsen.
Kamilla Miskowiak (28)
is a Psychologist with degrees from the University of Copenhagen
and Oxford University, and a Ph.D. from Oxford. Her current
research is based on her previous projects on how EPO (erythropoietin) may help rehabilitation from brain damage in animals,
and how antidepressant treatment affects the processing of
emotional information.
Against this background, she is now investigating the extent to
which EPO may prevent the degradation of brain tissue (as seen
in depression), including examination of whether prolonged treatment reduces the symptoms and improves the learning ability of
patients with depression and bipolar disorder.
Emil Loldrup Fosbøl (27)
graduated as a Doctor of Medicine in summer 2009, and submitted his Ph.D. thesis at the same time. His research is conducted
in the Cardiology Department at Gentofte Hospital. Based on clinical epidemiology, it focuses on risk factors in the use of over-thecounter painkillers in healthy humans. He has already published
a number of articles on this subject in prominent international
journals, and his research findings about the risk of cardiovascular
complications from mild analgesics has received considerable publicity, both in Denmark and abroad.
Mads Toudal Frandsen (28)
studied physics at the University of Copenhagen, has a Ph.D. from
the Niels Bohr Institute and the University of Southern Denmark,
and is now employed as a post doc. at Oxford University. His
research aims to contribute to the understanding of the Universe's
'dark matter', which is known to possess mass but does not emit
or reflect light. Mads T. Frandsen's focus is on the development
and testing of mathematical models that can be used to explain
the existence of dark matter in the Universe. In part, this is tested
on the basis of the experiments conducted in the Large Hadron
Collider at CERN.
Based on its strategy for donations, which was amended at the
Foundation's strategy seminar in 2009, the Lundbeck Foundation
will focus its 2010 awards on key support areas in the strategy, and
on the research leaders of the future. New research centres will
therefore not be funded in 2010, as the Board has chosen to
prioritise funding for fellowships, for which a total of DKK 100
million has been earmarked in 2010.
Future expectations
In 2007, the Foundation decided that grants for the three-year
period 2008-2010 would amount to a total of approx. DKK 1
billion. This strategy has been maintained despite fluctuations in
the Foundation's annual results in the wake of the 2008 financial
crisis. In 2008 and 2009, DKK 328 million and DKK 340 million
were awarded, respectively. A similar level is envisaged for 2010.
THE LUNDBECK FOUNDATION 2009│10
GRANT-MAKING POLICY
grant strategy
The Lundbeck Foundation, through the awarding of grants, aims
to strengthen Danish research of the highest quality in biomedicine
and natural sciences.
Neuroscience is a core area for the Foundation, but projects within
other areas are also supported. However, the Foundation has
reservations in areas where other Danish foundations and institutions have special interests and obligations.
Projects outside the fields of biomedicine and natural sciences are
only funded to a very limited degree, and it is normally a precondition that they are scientific in nature.
Re.: Biomedical Sciences
The Lundbeck Foundation divides biomedical research into three
levels: basic research, applied (translational / clinical) research and
research within epidemiology and prevention of disease.
Basic research is generally perceived as research into disease
mechanisms, and consequently focus on a particular topic is not
required for applications within this area.
Applied research and prevention research
Within these areas, there will be more emphasis on projects with
immediate or expected future relevance for or impact on neuroscience.
The Lundbeck Fundation is committed to maintain and exploit
the opportunities and freedom of a private foundation as being
independent of special interests and public institutions.
Instruments:
The Lundbeck Foundation supports high-quality research in
biomedicine and natural sciences carried out in Denmark or by
Danish researchers abroad through a number of instruments:
Applications can be submitted for:
• Research projects
• Visiting researchers and travel stipends
• Junior Group Leader Fellowships
• Grants of Excellence in Neuroscience
Research prizes:
The prizes cannot be applied for but nominations are accepted
from leading scientists at Danish universities.
• Talent Prizes
• Research Prizes for Young Scientists
Research in epidemiology
and disease prevention
Translational and clinical
biomedical research
Assessment of applications and nominations
All project applications are assessed by one of the Foundation’s
two International Scientific Advisory Committees, i.e. biomedical
sciences or natural sciences.
Assessment of other applications to the Foundation takes place
in collaboration with independent external experts according to
generally accepted standards of impartiality and competence.
Basic research including physics and chemistry.
Research into disease mechanisms
Re.: Natural Sciences
Within the natural sciences the Foundation supports non-biological research in chemistry and physics.
The Fundation also supports research in subjects that border on
the biomedical sciences. Such research is assessed by the Foundation’s International Scientific Advisory Committee for biomedicine.
Research funding
The Lundbeck Foundation’s overriding criterion for granting
research funds is solely based on the quality of the research.
This relates to the quality of the project’s scientific content, the
applicant's qualifications and to the host institution's academic
focus on high quality.
As a general aim, grants must make a difference. Thus, the
Foundation devotes relatively large financial resources to a small
number of projects, rather than small amounts to a large number
of projects.
The effects of the grants are monitored and evaluated.
General guidelines / conditions
The recruitment of scientists is supported through the granting
of scholarships and Ph.D. stipends, in addition to projects that
stimulate interest in biomedicine and natural sciences in general.
Scholarships are awarded only for research, though not when the
research is an integral part of an education.
Project funding is provided in the form of salaries for academic
staff (e.g. post docs.) technical personnel and to a lesser degree to
project relevant equipment.
As a general rule, the Foundation places no restrictions upon the
patenting or commercialisation of research results from project
grants.
Research projects conducted by private businesses and trials of
commercial drug candidates are not eligible for funding.
THE lundbeck FOUNDATION PROFESSORSHIPS AND
THE junior group leader fellowships
Junior Group Leader, Post doc., Ph.D. Søren Gøgsig Faarup Rasmussen,
University of Copenhagen, Institute of Neuroscience and Pharmacology.
Established 2009
Junior Group Leader, Assoc. Professor, Ph.D. Steen Brøndsted Nielsen,
University of Aarhus, Institute for Physics and Astronomy.
Established 2009
Junior Group Leader, Assoc. Professor, Ph.D. Martin Røssel Larsen,
University of Southern Denmark, Institute for Biochemistry and Molecular Biology. Established 2009
Junior Group Leader, Ass. Professor, Ph.D. Lene Niemann Nejsum,
University of Aarhus, Institute for Molecular Biology.
Established 2009
Junior Group Leader, Assoc. Professor, Ph.D. Troels C. Petersen,
University of Copenhagen, Niels Bohr Institute.
Established 2009
Junior Group Leader, Professor, Ph.D. Jakob Balslev Sørensen,
Institute of Neuroscience and Pharmacology, Copenhagen University,
Established 2008
Junior Group Leader, Assoc. Professor, Ph.D. Jakob Nilsson,
Biotech Research and Innovation Centre (BRIC), Copenhagen University,
Established 2008
Junior Group Leader, Assoc. Professor, Ph.D. Sune Toft,
Niels Bohr Institute, DARK, Copenhagen University,
Established 2008
Junior Group Leader, Assoc. Professor, Ph.D. Anja Groth
Biotech Research and Innovation Centre (BRIC), Copenhagen University,
Established 2007
Junior Group Leader, Assoc. Professor, Ph.D. Henrik B. Pedersen
Institute for Physics & Astronomy, Aarhus University,
Established 2007
Professor, M.D., M.Sc., Ph.D. Shohreh Issazadeh-Navikas
Biotech Research and Innovation Centre (BRIC), Copenhagen University,
Established 2007
Professor, M.D. Jens Bukh
Subject: ‘Experimental studies of human viruses and infections’,
Institute of Medical Biology and Immunology, Copenhagen University,
Established 2006
Professor, Director of Research, Ph.D. Lis Adamsen
Subject: ’Clinical nursing’, Institute of Public Health, Copenhagen
University, Established 2006
Professor, M.Sc., Ph.D. Ole Nørregaard Jensen
Subject: ’Protein mass spectrometry’, Institute of Biochemistry and
Molecular Biology, University of Southern Denmark, Established 2004
THE LUNDBECK FOUNDATION 2009│10
THE FIRST GENOME FROM A PREHISTORIC HUMAN
the first genome from
a prehistoric human
By Professor Eske Willerslev
Basic Research Centre for GeoGenetics, University of Copenhagen
"We can do it!" I shout, and sit up in bed. I'm still not quite
awake. "Go upstairs and work," snaps Ulrikke, sleepily. She turns
around and goes back to sleep. I've got a new idea and, as is often
the case, it came to me in the middle of the night. I rub my eyes
and jump out of bed. It's just past five in the morning. "Should I
e-mail Rasmus and Tom?" I wonder. Experience tells me that not
all of my night-time ideas are equally constructive. But I believe in
this one. I write an e-mail. "I think we should consider sequencing
the whole core genome from the hair sample of the 4,000-year-old
Greenlander," I write, and return to Ulrikke in bed. It's a pretty
wild idea. Until now it has only been possible to sequence mitochondria genome from old material. This small genome, inherited
through the maternal line, is only 16,000 base pairs long. By comparison, the core genome that I have in mind, 50% of which stems
from the father, 50% from the mother, is approximately 3 billion
base-pairs long. The decision to sequence the core genome of a
living person for the first time was taken two decades ago. In the
end, it took 14 years and cost more than DKK 15 billion. Now I'm
thinking about doing the same, but for a person who died 4,000
years ago, and whose DNA is about as intact as Berlin at the end of
World War II. "Maybe it's one of my less realistic ideas," I ponder
as I fall back asleep.
took place about 5,500 years ago. Multiple traces of early hunter
settlements have been found all the way from Alaska in the east to
Greenland in the west. But who these early Arctic explorers were,
and whence they came, no one seems to know for sure. Some surmise that the first humans in the Arctic were ancestors of today's
Inuit who now populate the easternmost corner of Siberia, Alaska,
Arctic Canada and Greenland. Some argue that these palaeo-Eskimos, as they are called, were related to Native Americans. Others
believe they were close kin of the Siberian peoples.
Close, but no cigar
It all started when I read about the first humans in the Arctic. This
inhospitable and treeless landscape, which stretches along the coast
of the ice sea in the northern hemisphere, was the last of Earth's
land areas to be permanently inhabited by humans. This probably
The hunt for the first people in the Arctic
"The helicopter has crashed! The helicopter has crashed!" shouts
Claus. It's summer 2006, three years after my visit to the National
Museum. We're at Station North in North-east Greenland - the
last outpost before the wilderness that is Peary Land, the northern-
I try to find answers to my questions by visiting the Arctic
archaeologists at the National Museum, but am told that, despite
countless archaeological finds, only one single site has contained
human remains - four bone fragments, found on the ice fjord in
West Greenland. "Perhaps they buried their dead on the sea ice,"
suggests Bjarne Grønnow, the person in charge of Greenland
archaeology, by way of explanation for the scarcity of human
material. I am determined to test the human bones for DNA, but
Niels Lynnerup, from the Anthropology Laboratory that houses
the four pieces, refuses my request. The bones are too valuable
it would seem. They are also in an incredibly poor state, so it's
doubtful whether any DNA has been preserved.
17
THE LUNDBECK FOUNDATION 2009│10
most land area on Earth, just 740 km from the North Pole. We're
heading out into this wilderness to spend a month and a half
searching for human remains. But the helicopter has crashed in a
snowstorm somewhere out there. A rescue team has been sent to
find the pilot. "We need to change our plans," says Claus Andreasen, from the Greenland National Museum in Nuuk. "We need to
use a small aeroplane instead."
Despite trekking over the ice thin in the wilderness of Peary Land,
Claus and I find no remains from the earliest human inhabitants
of Greenland. We find several settlements but all we excavate, with
great difficulty, are stone tools and animal bones. It's possible that
the bones retain traces of ancient human DNA from the last time
they were touched. Although DNA is a highly unstable molecule
and degrades over time, the rate of degradation slows significantly
at temperatures as low as those in Peary Land. Every time he digs,
Claus therefore dutifully pulls on the "space suit" as well as a face
mask and disposable gloves – in order to minimise the possibility
of him contaminating a sample with his own DNA. It's a cold task.
By day, the temperature hovers around the freezing point – even
though it's mid-July. We return home with more than 100 objects.
Unfortunately, not a single one of them proves to contain human
DNA. All we find is animal DNA from the bones themselves.
The forgotten tuft of hair
I have almost given up hope of discovering where the first humans
in the Arctic came from – and then in autumn 2008, I meet with
Morten Meldgaard, Director of the Natural History Museum. The
meeting is principally about reindeer, but our conversation soon
turns to Greenland and the earliest humans. Morten's father,
Jørgen, was one of the archaeologists who established the presence
of a Stone Age in the Arctic, and Morten himself has participated
in several excavations as a zoo archaeologist. "I'm pretty sure
the National Museum has a tuft of human hair from the earliest
Greenlanders from a dig in 1986," he says. I refuse to believe it.
"No, that can't be right." I'd talked to Bjarne Grønnow in person
in 2003 after all, and was told that only four fragments of human
bone had been found. But Morten insists, and doubts set in. He's
known for his remarkably good memory.
Soon after, we are in Bjarne Grønnow's office at the National
Museum – and in front of us lies a huge clump of long, black hair.
I don't know whether to laugh or cry. I froze my butt off in Peary
Land to find something even remotely similar to this, and here it is,
THE FIRST GENOME FROM A PREHISTORIC HUMAN
just 10 minutes by bike from where I live. My irritation is quickly
replaced with enthusiasm for the rediscovery of this valuable
material. Since the hair is officially owned by Greenland, we have
to ask the permission of my old expedition friend, Claus Andreasen, before we can run any tests – we get it right away. Claus wasn't
aware the hair existed either. Nevertheless, he reminds me that the
Greenland trip was certainly not in vain, since we did bring back
many valuable specimens. In my mind, I thank Morten Meldgaard
for his good memory and Claus for his benevolent attitude towards
new scientific projects. Without them, this would never have been
a success story. The hair is dated. It's 4,000 years old.
The mitochondria genome
A couple of years earlier, a new type of technology had revolutionised molecular biology. It consists of different sequencing platforms
– 454, Solexa, Solid, etc. – collectively referred to as "Second
Generation High Throughput Sequencing". Without getting too
technical, there are two particularly amazing things about these
technologies: i) They liberate us from our dependency on classic,
primer-based PCR technology, which set clear limits for how short
DNA pieces could be for testing purposes (i.e. they had to include
both primer binding sites and an informative sequence in between). This has enormous importance for the study of DNA from
ancient material, in which the molecules are heavily fragmented. ii)
In just a few days, it is possible to sequence in parallel millions and
billions of nucleotides, which means that whole genomes can be
sequenced within a manageable time scale.
Naturally, we in Copenhagen are not the only ones to see the potential in these new technologies. While we are struggling to raise
money for just one of these highly coveted machines, people from
Max Planck and the USA have already bought four machines each
and started to sequence the genomes of extinct species. Luckily for
us, both the Germans and the Americans think too traditionally.
They extract DNA from old bones, as studies of ancient materials
have indeed shown that bones contain the most endogenous DNA.
The result is that most of their sequences are from microbes. Unlike traditional, primer-based PCR technology, this is not "target
sequencing". You get sequences from the most prevalent DNA in
the extraction – and in the case of bones, that means bacteria.
Tom Gilbert, a post doc. in my group, has an ingenious idea:
"What's important isn't the absolute quantity of DNA, but the
relative proportions of endogenous and polluting DNA," he
exclaims. "Bones and teeth are full of microscopic holes that are
penetrated by micro-organisms over thousands of years – but what
about hair?" Hair is made of a different material, keratin, which
doesn't have the porosity of bones and teeth. This means that most
of the pollution would sit on the surface. The idea is good, and
worth testing. Tom buys some toilet cleaner from the local supermarket, and a piece of mammoth hair is placed in it. The DNA is
extracted from the cleaned hair and run on a 454 machine in the
USA. Bingo! 90% of all the sequences stem from the mammoth.
Without the grant from the Lundbeck
Foundation, all would have been lost, but
now we have at least a chance of beating
the Germans and Americans in the race
to sequence the first 'old' genome.
In autumn 2008, we sequence the first complete mitochondria
DNA from the 4,000-year-old Greenlandic hair samples. The
article is published at express speed in Science. We are the first
to sequence the entire mitochondria genome from a prehistoric
human – beating the Germans from Max Planck by only a few
months. The result isn't just a technological breakthrough. It also
shows that the maternal line to the old Greenlanders is closer to the
people of the Aleutian Islands - the islands lying between Siberia
and Alaska - than it is to modern Greenlanders. This suggests that
the first people in Greenland are not direct ancestors of the modern
Inuit people. However, all genes in the mitochondria are linked,
and can therefore, in an evolutionary context, only be perceived as
a single gene. In other words, we have to be very cautious before
drawing conclusions.
The core genome
The next day, we discuss my middle-of-the-night idea to sequence
the whole core genome from the 4,000-year-old Greenlander.
Rasmus (Morten Rasmussen, my Ph.D.-student) and Tom don't
think the idea is stupid at all. It should be possible. However, both
the Germans and the Americans have a very big head start, and
we lack both machines and money. I apply for more funding, but
in vain. The responses are always the same. Would it work? What
would the ordinary Dane in the street use it for? Each time, I reply
that I don't know the commercial significance and that there's no
guarantee it'll work, but the project has the potential to revolutionise science and generate massive international interest in Danish
science. My arguments seem to fall on deaf ears.
Then two amazing things happen almost simultaneously. Frederik
Paulsen, Director of the Ferring Group hears about the project,
recognises its potential and decides to donate DKK 250,000 of
his own money. It's nowhere near enough, but a fantastic gesture,
and means we can get the ball rolling. Shortly after that, I receive
a reply to an urgent application to the Lundbeck Foundation. The
Foundation also sees great potential in the project, and understands that time is running out. They've decided to donate DKK
1.5 million. Financially, we are up and running. Without the grant
from the Lundbeck Foundation, all would have been lost, but now
we have at least a chance of beating the Germans and Americans in
the race to sequence the first ’old’ genome.
I put everything I have into it. There can be only one winner in
this race - the one that comes first. The Germans and Americans
have budgets of DKK 50 million, and have everything they need
’in-house’ – machines, molecular biologists, bioinformaticians, etc.
I may only have DKK 1.75 million, but I've also got an ace up
my sleeve. Morten Rasmussen is one of my Ph.D.- students and
undoubtedly one of the most gifted people I’ve ever met. Some
might argue that one man doesn’t count for much – but they’d be
wrong. Morten and I have the perfect working relationship, and
we’ve pipped other more well-heeled researchers at the post on
several occasions.
Morten and I divide the work between us. He takes care of the
laboratory details while I concentrate on the big picture. I get Jun
Wang, head of BGI in China, the world's largest sequencing unit,
interested in the project, so that's the machinery in place. At the
same time, I secure assistance from some of the world's best bioinformaticians and population genetics researchers, including our
own Anders Krogh and Søren Brunak. I procure DNA extractions
from Greenlanders, Native Americans and Siberian peoples, so we
THE LUNDBECK FOUNDATION 2009│10
can simultaneously generate comparative population-genetic data.
All of the participants understand the importance of the project
and give it their all – day and night. To solve the problem of
contamination of DNA samples after they leave the special clean
laboratories in Copenhagen, we mark every single sequence with a
unique code, so we can tell which DNA sequences are subsequently introduced in China. We also solve the problem of deamination
damage in the DNA, which causes sequence errors, by multiplying
the genomic DNA with a polymerase enzyme that cannot read
over the damaged bases. Everything is running like clockwork –
until we run out of DNA samples. We need more hair. Everything
grinds to a halt. The delay lasts for what seems like an eternity. I
shuffle about impatiently. Fortuntely we're finally allowed to take
another bit of hair.
We run the project. The volume of data is so enormous that we
have to use the computer clusters at both the University of Copenhagen and The Technical University of Denmark. We sequence the
possible 80% of the damaged genome, the average sequence length
of which is at a paltry 55 base pairs with a depth of 20x – in other
words, on average 80% of the genome is sequenced 20 times, making it possible for us to recognise both the mother’s and father's
contribution. We manage to assemble an enormous jigsaw puzzle
of 3.5 billion small pieces into a total genome. In other words,
we now have a genome from a 4,000-year-old man, the quality of
which is almost as good as if it was from a living person. This is
not only the first sequenced genome from a prehistoric human, but
the first in depth-sequenced genome from anything dead of any
species. It's wonderful!
The unidentified migration
The information we are able to derive from the genome is incredible too. We can see that the hair stems from a man, that he
probably had brown eyes and brown skin, was of compact build,
had a tendency towards baldness, had dry earwax and shovel-shaped incisors. Even though his ancestors had only been in the Arctic
for approx. 1,500 years, he had already genetically adapted to life
in a cold climate in several ways. He was inbred, which corresponds to cousins marrying and suggests that his people lived in
small groups isolated from each other. His closest relatives aren't
in the New World – i.e. they're neither Inuit nor Native American
– but three Siberian peoples, one of which now lives more than
2,000 km from the Bering Sea that separates the New and Old
World. In other words, this man has no living descendants in the
THE FIRST GENOME FROM A PREHISTORIC HUMAN
New World, where he ended his days. His genome is proof that
5,500 years ago, migration took place from Siberia to America and
on to Greenland, a migration of which previous research has been
blissfully unaware, a migration completely different from and
independent of the ones that gave rise to today's Native Americans
and Inuit. This, for me, is the true joy of working with fossil DNA.
Not only can we reconstruct important components of the people
from a culture of which no biological traces remain other than four
bones and some tufts of hair, but we can also shed light on parts of
human history and evolutionary development that modern genetic
studies would not have been able to reveal because those people left
behind no descendants that survive to this day. We had discovered
a previously unknown migration to the New World. The study
throws up the inevitable question of how many other previously
unknown migrations have taken place. The 4,000-year-old Greenlander is dubbed "Inuk", meaning "man" in Greenlandic. For
many years to come, we'll obtain further information about Inuk
as we continue to decode our own DNA. Each time, we'll return to
the genome to see what this new information tells us about Inuk.
Inuk becomes world famous
The story of the prehistoric human Inuk and his genome makes
the front cover of the journal Nature. The same volume carries a
"News and Views" article on the discovery, as well as article profiling my Danish research group and myself. What more could you
want? We won the race to be first to sequence the genome of an
extinct organism. The story of Inuk received the most international
press coverage in the University of Copenhagen's long history, with
more than 200 million potential readers from newspapers alone.
Inuk's longer term legacy is hard to predict. The possibility now
exists of exploring our molecular past and pinpointing the advent
of various phenomena, e.g. genetic predisposition to given diseases
or the selection of genes during the domestication of horses, cows,
etc. The potential is vast. In the short term, the story has given
Danish research huge international attention and advertising, the
value of which is difficult to quantify. The story of Inuk exemplifies
the essence of what basic research is all about – international attention and unpredictable scientific potential. Yet it is far removed
from the government's battle cry: "From research to invoice",
which has made it difficult in Denmark to find money for projects
like this. Fortunately, funders like the Lundbeck Foundation still
recognise the need for basic research and understand the importance of being first to make a breakthrough.
In this article, Dr. Lajos Balogh, who is the editor-in-chief of the scientific
journal Nanomedicine NBM, gives an introduction to the world of nanomedicine,
the subject for the Lundbeck Foundation's Centres of Excellence 2009
nanomedicine ‒ an introduction
In the next decade, Nanomedicine will reform our understanding of biology and
transform clinical medicine – it will forever change how we diagnose and treat patients.
Imagine that you cut yourself accidentally. You pull out a vial; pour
some liquid over the wound. The bleeding stops in 5 seconds, the
wound heals quickly and without complications. Or, you hurt your
eyes in an accident and now your vision is blurred. Your doctor
borrows a few cells from you, constructs a new layer of transparent
skin and repairs your vision by replacing the scarred corneal epithelium with a synthetic material, actually made of you. Running
a personal DNA profile allows for prescribing a treatment just for
you; your personal medicine, which is effective only for you, is prepared in a day by the nearby nanopharmacist. These are not sci-fi
scenarios, but existing experimental procedures in nanomedicine.
nanoscience, nanotechnology, nanomedicine
The original meaning of ’nano’ is 10-9 (or 0.000000001) without
a dimension. Consequently, ‘nano-scale` could be measured using
any dimension, but always very small. For length, measured in
meters, it usually means 1-1000 nanometer, whereas 1000 nm
is equal to 1 micrometer, 1000 micrometer equals 1 millimeter
and so on, (for comparison, the diameter of a red blood cell is
7.5 micrometer, or 7500 nm). Still, the relations between science,
technology, medicine and business are always the same, regardless
whether it is “nano” or not “nano”. Nanoscience is a multidisciplinary science studying nanoscale objects and structures to understand and control matter at the nanoscale. Nanomaterials are
NOT new magical materials, but “old” ones on a different scale
(“nano-scale”) with properties that do not exist outside of the
nano-range. Accordingly, nanotechnology is the application of
nanoscience to study, develop, create, and use materials, devices,
machines, and techniques for manufacturing nanomaterials, nanostructures and integrated systems. It works by applying engineering
principles and developing processes and technology, tools and
methods or methodology for nanoscale R&D and the manufacturing of nanomaterials, devices, machines and techniques.
Nanomedicine exploits and builds upon novel research findings in
nanoscience, nanotechnology, biology and medicine; it unifies the
efforts of scientists, engineers and physicians determined to apply
their latest research results to translational and clinical medicine to
develop novel and better approaches and solutions to health-related
issues. Nanomedicine is not a separate discipline, rather a realm
that nanoscience and nanotechnology share with life sciences (biology and medicine), a region where they overlap and interact with
each other. This area includes not only various applications of nanotechnology in life sciences. Biology and medicine also breed new
research in nanoscience. In other words, the world of nanoscience
and nanotechnology is not vertical; it is horizontal and joins together a number of disciplines, which include life sciences.
21
THE LUNDBECK FOUNDATION 2009│10
the nanoscopic range
Many of the “nano” properties are based on the collective behavior
of primary objects (atoms, molecules, macromolecules, particles,
proteins, etc). Just like individuals behave differently when they
are alone, from when they are part of certain groups and share an
experience, atoms and molecules behave differently when they
are held together in small groups by physical and physicochemical
forces and share electrons. What is on the surface of nanoparticles
and what is around them is also very important. Here is a simple
explanation: the surface of a sphere with 1 cm diameter is 3.14 x
10—4 m2, but if we calculate the total surface of d = 3.9 nm solid
spheres made of the same material and of the same total mass, the
result is around 826 m2.
Consequently, what is on the much larger surface of the latter
will have more impact than what is on the surface of the 1 cm.
diameter sphere.
As nanoparticles grow in size, their relative differences become
smaller and smaller with the addition of the next object until
they reach the “bulk” state. Simultaneously, nanoscale properties
also gradually disappear. In the bulk state, properties of a certain
macro-scale object will not change by adding one more molecule
or atom to it, while on the nanoscale they do change. As an example, gold nanoparticles are red, fluorescent, chemically reactive,
and soluble in water, but bulk gold, as we all know, is a yellow inert
metal, which is insoluble in water. The new nano-scale properties
of well known materials can be utilized in many areas of nanomedicine.
major directions in nanomedicine
The last few years have seen unprecedented advances in the field
of biology. The decoding of the human genome, coupled with
improving gene transfection technologies offer great opportunities
for treating disease. In biologic analysis, lab-on-a-chip methods
(e.g. ultra small scale diagnostic devices, large, multiple arrays that
can detect thousands of signatures simultaneously) have surpassed
earlier ex-vivo and in-vivo detection methods by magnitudes, and
provided greatly improved diagnosis, while also aiding important
toxicology efforts, such as detection of anthrax spores at the nanogram scale, identification of ten-to-twenty cancer cells in 100
microliters of blood, etc. In medicine, improvements in targeted
drug delivery, imaging and therapy have led to so successful interventions in cancer therapies, that cancer is no longer the number
one cause of mortality in the US.
22
NANOMEDICINE – AN INTRODUCTION
Despite these achievements there is still a serious need to improve
healthcare, and a lot to do. In 2007, in the United States alone,
the direct medical cost for cancer was about $90B, and the direct
medical cost for diabetes was about $116B. The annual medical
care cost for spinal cord injury was about $1.5B; the total costs are
estimated to about $10B/yr. In order to remain physically active,
approximately 200,000 people received hip implants and 300,000
people received knee implants. The average lifetime of current orthopedic implants is only 10 – 15 years; and the cost of an implant
varies but in 2010 it is roughly $20,000.
Let me give you three exciting (and subjective) examples of ongoing revolutionary nanomedicine research.
(1) Engineered cell sheets are prepared by culturing cells at 37o C
on temperature-responsive surfaces (Masayuki Yamato). Then the
cultured cell sheets are harvested by simple temperature changes
from 37o C to 20o C, when the cell sheet floats to the surface of the
Petri-dish, then placed by the eye-surgeon on the appropriate living
surface to recover function. Various cell sheets such as corneal
epithelium, corneal endothelium, skin, periodontal ligaments,
oral mucosal epithelium, urothelium, and cardiomyocyte tissues
have already been fabricated. Clinical treatments have already been
initiated using both corneal and oral mucosal epithelial cell sheets
for the treatment of patients with corneal surface diseases.
(2) Wherever cancer cells are active, metalloprotease enzymes
(MMP-2 and MMP-9) are also very active, so mapping MMP2 and MMP-9 activities allows the visualization of cancer cells
(Roger Tsien). When labeled activable peptides penetrate cells
in the presence of MMP enzymes, they are cut by these active
metalloproteases and thus become activated and fluorescent. This
approach has the potential to revolutionize cancer surgery because
the surgeon removing the primary tumor will be able to see what
additional tissue has to be removed, instead of making assumptions
based on experience.
(3) Short and water-soluble peptide sequences were designed and
synthesized (Rutledge Ellis-Behnke). These peptides self-assemble
into layers and, when exposed to a wound, form a strong gel within
seconds thereby physically blocking the bleeding. The material
then gradually deteriorates as new tissue is forming. The completely transparent gel can also be used to carry out bloodless surgeries.
”One of the major impacts of nanotechnology will be the
development of ultrasensitive methods that will help us learn
more about biologic mechanisms and will enrich our
knowledge of biology.”
Other current R&D efforts focus on early diagnosis, early detection and treatment of disease (especially cancer), bone and tissue
regeneration, development of intelligent nanobiomaterials for cell
therapy to improve organ function, safe and affordable therapeutic
strategies to regenerate neural tissues, hollow fiber membranes to
perform kidney functions, cochlear and retinal implants, new miniature power sources, repair of articular cartilage, new anti-microbial materials, skin, tissue and nerve regeneration, targeted drug
delivery, functional imaging agents, novel anticancer therapies, and
so on.
nanomedicine as business
Nanomedicine is beginning to have an enormous impact on the
pharmaceutical market. It is estimated that life sciences and healthcare products, enabled by nanoscience and technology, currently
represent a $1 billion plus market in 2009, primarily in the fields
of medical devices, implants, imaging and diagnostics, with annual
markets of billions of dollars predicted within ten years. Major
nanomedicine development directions reflect the health needs
listed earlier and the opportunities in nanoscience and nanotechnology. First generation products on the market include nanoparticulate pharmaceuticals, biocompatible (long lifetime) implants,
and anti-bacterial coatings for medical supplies, and healing wound
dressings. Nanomedicine will change the way pharmacologic
business is done. Personalized medicine, based on the individual
biomedical profile of a particular patient, will require manufacturing of small quantities of nanomedicines by experts. A DNA
profiling today costs about $5000, and is presently too expensive
for routine hospitalizations, but it is projected that in the not too
distant future the cost of sequencing a person’s genome will drop
below $1000, less than the present price of colonoscopy.
We have just started to witness this cutting edge technology appearing in medicine. One of the major impacts of nanotechnology
will be the development of ultrasensitive methods that will help
us learn more about biologic mechanisms and will enrich our
knowledge of biology. Support from foundations like the Lundbeck Foundation is crucial to move the field forward, as inventions
cannot be scheduled, only observed. In the following articles, the
three Nanomedicine Centres of Excellence, granted by the Lundbeck Foundation will introduce their projects and how they plan to
exploit the vast possibilities found in research and development on
a very small scale.
Biomembranes which will be studied and manipulated at nanoscale in CBN (The Lundbeck Foundation Centre for Biomembranes in Nanomedicine) play a critical role in our life. Proteinmembrane and membrane-membrane interactions control signal
transmissions through biological membranes and learning much
more about these is crucial for successful drug delivery.
Cancer stem cells are thought to be responsible for the recurrence
of cancers and may be one reason for metastasis and eventually
cancer-related mortality. As cancer stem cells are usually resistant
to therapies aimed at cancer cells, the ability to address cancer stem
cells will be a fundamental step forward in cancer therapies that
will be addressed by NANOCAN – The Lundbeck Foundation
Nanomedicine Research Centre for Cancer Stem Cell Targeting
Therapeutics.
Individualized management (prevention, diagnosis and treatment) of cardiovascular and musculoskeletal diseases as well as
tissue damage and regeneration will be addressed by LUNA – The
Lundbeck Foundation Nanomedicine Centre for Individualized
Management of Tissue Damage and Regeneration. This direction
is very significant, because cardiovascular diseases are now more
prevalent than cancer.
The publication rate of nanomedicine related papers is exploding
– it is growing faster than exponential since 2000. As Editor-inChief of Nanomedicine: Nanotechnology, Biology and Medicine
(Nanomedicine: NBM) I would like to share my excitement and
optimism about the future of these centres. I hope that within a
short time we could welcome publications about true medical
breakthroughs from all three of them in this international, peerreviewed journal, which follows the latest advances in the field of
nanomedicine.
We at Nanomedicine: NBM believe that nanomedicine will have a
profound impact on future medical practice. However, we strive to
promote the view that nanomedicine as a solution is neither better
nor worse – it is DIFFERENT.
23
THE LUNDBECK FOUNDATION 2009│10
CENTRES OF EXCELLENCE 2009 – NANOMEDICINE
big opportunities in
a small world
individualized prevention,
diagnostics and treatment
imbalance between tissue damage and tissue
regeneration in disease
The aim of the new nanomedicine research centre is to develop novel clinically relevant nanobased technologies within drug design,
drug delivery, bio imaging and tissue engineering and to support
individualized prevention, diagnosis and treatment of cardiovascular and musculoskeletal diseases. The dramatic population ageing
in Western societies poses a major burden to their healthcare
systems and health economics due to an increased number of
patients suffering from chronic diseases. Cardiovascular- (CVDs)
and musculoskeletal diseases (MSDs) are two of the most significant contributors to this burden. Present limited success in the
management of CVD and MSD is most likely a consequence of
their multifactorial pathogenesis, where disease development is
determined by environmental factors as well as individual susceptibility. Consequently, there is a huge need for development of new
A human stem cell cultured in a nanoporous biomaterial. (J.V. Nygaard, iNANO)
and novel approaches to individualized and targeted treatment of
these important diseases. This goal can only be achieved through
combining cutting-edge international competences within the areas
of nanoscience and translational medicine.
a strong basis
LUNA is part of a broader nanomedicine initiative established in
Aarhus and builds on a number of technological platforms developed through existing cross-disciplinary projects established at the
Faculty of Health Sciences and the Interdisciplinary Nanoscience
Centre, iNANO. The LUNA project will benefit from these strong
collaborations that have set the stage for future nanomedicine
research in Aarhus. The project will be headed by leading scientists
covering the areas of translational biomedical research, state-ofthe-art nanoscience, biomedical imaging, structural and molecular
biology.
luna – the lundbeck
Professor Allan Flyvbjerg,
The mechanism behind the
for individualized management
the Faculty of Health Sciences
and tissue regeneration in disease
regeneration
Interdisciplinary Nanoscience
foundation nanomedicine centre
of tissue damage and
Aarhus University Hospital and
and professor Jørgen Kjems,
Centre (iNANO) Aarhus University
imbalance between tissue damage
DKK 30 million in the period 2010-2105
26 senior researchers and
10 Ph.D.-students
www.nanomedicine.dk
”Clearly, nanomedicine holds an
enormous potential, also for
development of new treatments.
Research in the field is greatly
needed, and therefore, it is a
visionary and timely strategy of the
Lundbeck Foundation to support
the nanomedicine research area.”
Model of C5 pattern recognition molecule in complex with an inhibitor
(N.S. Laursen)
“Clearly, nanomedicine holds an enormous potential, also for development of new treatments. Research in the field is greatly
needed, and therefore, it is a visionary and timely strategy of the
Lundbeck Foundation to support the nanomedicine research area.
Nanomedicine is a cornerstone of the research strategy of Aarhus
University, which has now been replenished with vital resources,”
says Professor Allan Flyvbjerg.
“The centre will set the very best research team by recruiting post
docs and Ph.D.- students on an international basis. Furthermore,
the research groups forming part of the centre all have broad international collaborations, which will contribute to the establishment
of a strong research environment within LUNA”, adds Professor
Jørgen Kjems.
restoring balance
Central for the centre’s work is the hypothesis that cardiovascular
and musculoskeletal diseases are caused by an imbalance in tissue
damage and the body’s natural ability to repair or rebuild damaged
tissues. Thus, an important part of the centre’s work is focused on
determining the central mechanisms causing these imbalances.
Furthermore, development of nanobased techniques to stimulate
tissue regeneration and to restore balance. The central hypothesis
is that a group of newly discovered molecules ('pattern recognition
molecules’) play a central role in the imbalance between tissue
damage and the capacity for regeneration and in part hold the
explanation for individual differences in susceptibility to disease
development.
The goal is, through cross-disciplinary research, to create new
knowledge and translate it into novel technologies that are expected to reduce the disease burden from cardiovascular disease and
musculoskeletal disorders through individualized prevention,
diagnosis and treatment. The planned projects will take advantage
of newly developed techniques from the nano-world to explore the
role of these molecules in the disease development in two significant diseases.
Furthermore, the collaboration between health- and nanosciences
will lead to the training of talented scientists with deep insight into
both fields, a competence which will be in heavy demand in the
future.
THE LUNDBECK FOUNDATION 2009│10
CENTRES OF EXCELLENCE 2009 – NANOMEDICINE
targeted treatment of
cancer stem cells using
nano carriers
smart missiles against cancer
In the recent past, a rare population of tumor cells has been discovered that shares the molecular coat and properties of stem cells.
These so-called cancer stem cells are resistant to most existing
therapies and highly metastatic. It is therefore thought that the
next generation of anti-cancer drugs has to aim at an elimination
of the cancer stem cells to decrease the number of cancer deaths.
The high degree of similarity between cancer stem cells and normal
stem cells, however, poses extraordinary challenges: it has to be
avoided that the anti-cancer drugs are harmful to the related normal stem cells, which are of critical importance for the regeneration
of tissues and organs in the human organism.
The research at NanoCAN aims at constructing smart nano-missiles that selectively kill cancer stem cells without exerting severe side
effects on normal stem cells.
“Now is the ideal time to start tackling this ambitious goal,”
explains Professor Jan Mollenhauer “Techniques and know-how in
the areas of nanotechnology and molecular biomedicine have
reached a point of convergence that for the time allows us to systematically assemble smart drugs in academic laboratories. This is a
fascinating new option to achieve rapid progress in this field.”
NanoCAN will concentrate its activities on breast cancer, which
is still causing the death of every fourth patient and is the leading
cause of cancer mortality among women. “The general strategies
of NanoCAN, however, can also be projected to other cancer types
or to direct drugs to normal stem cells for regenerative medicine,”
explains Jan Mollenhauer.
a kit for smart nano-missiles
“We will dissect the drugs into three parts, which includes a
targeting device, a killing device, and a delivery device. The three
”We hope that NanoCAN will provide
substantial and exciting progress for
developing new future anti-cancer
therapies and are looking forward
to making use of the research
opportunities opened to us by the
Lundbeck Foundation donation.”
The basic principle of the smart nano-drugs that are developed in the NanoCAN centre is that the nano-drugs are guided to the stem cells via nano-scaled
“radar”-structures. A selective drug, serving as the “missile” consecutively kills only the cancer stem cells (red), which cuts off supply for the cancer cells
(orange). Normal cells (blue) and normal stem cells (green) remain unaffected, avoiding severe side effects.
nanocan – the lundbeck
Professor Jan Mollenhauer,
research centre for cancer
University of Southern Denmark
foundation nanomedicine
stem cell targeting therapeutics
Institute of Molecular Medicine,
Targeted treatment of cancer
stem cells using nano carriers
DKK 35 million in the period 2010-2014
4 senior researchers and
7 Ph.D.-students
www.nanocan.dk
To find selective drugs, the NanoCAN centre will use cells with specific molecular fingerprints of cancer stem cells and normal stem cells. Via a highcapacity robotic workstation, each of the 20,000 human genes will be inactivated in the cells followed by a systematic scan for the effects. Frontline
high-complexity biochips are developed and used for gathering data with high molecular resolution.
parts are developed in parallel and will then be assembled into
the active drug. This will not only save time, but also allow us to
combine the different components with each other similar to the
LEGO system to find the most optimal configuration. It moreover
has the advantage that we can more easily exchange one of the
components in order to address another cancer type or normal
stem cells for regenerative purposes,” says Jan Mollenhauer.
The various elements of the nano-drugs will be encapsulated in
nanospheres. They will find their way to cancer stem cells by
use of structures on their surface that recognise structures on the
surface of cancer stem cells. The actual attack on the cancer stem
cell is performed by small pieces of RNA, so called silencing RNA
(siRNA) which is known to be able to turn off activated genes.
Thereby, specific genes in cancer stem cells can be inactivated.
finding the needle in the haystack
“With regard to drug delivery devices and RNA-nanotechnology,
we can profit from the groundworks that has been carried out in
the two Centers of Excellence MEMPHYS and NAC, which were
funded by the Danish National Research Foundation at the University of Southern Denmark. This is a good example of how an
investment into basic research provides new avenues for translation,” concludes Professor Mollenhauer.
One of the major remaining challenges is that all known surface
structures that allow for guiding drugs to the cancer stem cells are
also present on normal stem cells, which must not be harmed by
the drugs. The NanoCAN centre aims at recovering siRNAs that
selectively kill cancer stem cells.
The centre's strategy comprises the construction of cells with
molecular fingerprints discerning cancer stem cells from normal
stem cells and consecutively testing the possible killing effect of
the inactivation of each of the 20,000 human genes in these cells
via siRNAs. To carry out this search strategy, the centre will use
high-throughput robotics in conjunction with advanced biochip
formats.
“This theoretically allows us to recover drugs for personalized
cancer treatment, because the drugs are aimed at specific molecular fingerprints. The tumor of an individual patient can then be
tested for the presence of such a fingerprint, making it possible to
determine in advance if the patient will profit from the treatment.”
says Jan Mollenhauer. “We hope that NanoCAN will provide substantial and exciting progress for developing new future anti-cancer
therapies and are looking forward to making use of the research
opportunities opened to us by the Lundbeck Foundation donation.
THE LUNDBECK FOUNDATION 2009│10
CENTRES OF EXCELLENCE 2009 – NANOMEDICINE
communication between
nerve cells and signaling
between bacteria
new insights into cell communication for the
benefit of patients
The Lundbeck Foundation Centre for Biomembranes in Nanomedicine (CBN) will in the next five years answer fundamental
questions about how basic biological processes of cell communication take place on the nanoscale. Disturbances in cellular communication is a key element in the development of a myriad of
diseases – from bacterial infections to diseases in the human brain
such as schizophrenia and Parkinson's disease. The centre’s research
findings may eventually lead to entirely new principles for how we
diagnose diseases and develop drugs.
“We expect to get much closer to a fundamental understanding of
a range of diseases by studying the biological processes taking place
in the cell's outer barrier, the cell membrane. While classically
recognized mostly as an inert barrier, it is now established that in
both bacteria and human cells, the cell membrane plays a dynamic
key role in multiple basal cellular processes”, explains Ulrik Gether.
Through complex and yet poorly understood interactions, the
lipids of the membrane mediate, together with multiple embedded
membrane proteins, vital processes such as transport of nutrients
and ions in and out of the cell, cell-to-cell contacts and transmission of chemical signals between cells. Interestingly, these processes
exhibit surprisingly many similarities between bacteria and human
cells, which underline their fundamental importance to all living
organisms.
"In CBN, we will focus on our key areas of expertise, neuronal
and bacterial cell-to-cell signaling. We will examine two types
of interactions that control the signal transfer across biological
membranes - protein-membrane interactions and membranemembrane interactions right down to the single molecule level",
says Dimitrios Stamou.
from nerve cells to nano containers
Nerve cells communicate via use of chemical signaling molecules
(neurotransmitters) that are contained within vesicles – small
containers of nanoscale dimensions inside the cells. The vesicles
Biological membranes are the nanoscale boundaries that separate the cytoplasm of the cell from the extracellular environment and define intracellular
compartments. The figure illustrates signal transmission across biological membranes, which represents the scientific focus of CBN. Signals are typically
transmitted across biological membranes via transmembrane proteins such as transporters, ion channels and receptors. A second major mechanism of
signal transmission is endo/exocytosis of vesicles that may transport signaling molecules such as neurotransmitters or virulence factors.
cbn – the lundbeck foundation
Professor Ulrik Gether,
Communication between nerve
nanomedicine
and Pharmacology and Assoc.
bacteria
centre for biomembranes in
Institute for Neuroscience
Professor Dimitrios Stamou,
Institute for Neuroscience
and Pharmacology and
Nano-Science Center,
University of Copenhagen
cells and signaling between
DKK 34 million in the period 2010-2015
10 senior researchers and
15 Ph.D.-students
www. nanomedicine.ku.dk
”Taken together, we are convinced
that our efforts over the next 5 years
will lead not only to enhanced
understanding of signal transmission
across biological membranes but
also provide new strategies for
diagnostics and treatment of brain
disorders and infectious diseases.”
Visualization by confocal fluorescence microscopy of the dopamine
transporter in live rat dopaminergic neurons using the fluorescent cocaine
analogue, JHC 1-64. The chemical structure of JHC 1-64 is seen in the
background (Eriksen et al, J. Neurosci. 2009)
fuse with the nerve cell membrane in a process called exocytosis,
thereby releasing the neurotransmitters to the surroundings. The
transmitters exert their action by activating receptors in the cell
membrane of the adjacent nerve cell. The action of the transmitter is terminated by rapid re-uptake of the transmitter via specific
transport proteins in the cell membrane of the nerve cells. CBN
has a particular interest in the neurotransmitter dopamine that is
essential for our brain’s ability to regulate motivation, reward,
learning and voluntary movements. Aberrations in dopamine
function play a key role in several psychiatric and neurological
disorders including schizophrenia, drug addiction, ADHD (Attention Deficit Hyperactivity Disorder) and Parkinson’s disease.
"It is our goal to develop ultra-sensitive assays for detection of
individual molecules of receptors and transporters in the cell
membrane as well as novel nano-biosensors for dopamine and
related transmitters. This will dramatically increase our ability to
investigate nanoscale events at the cellular level and hence to
obtain deeper insight into the mechanisms governing communication between nerve cells and thereby improve our possibilities for
treating diseases where this communication is disturbed”, says
Ulrik Gether.
similarities between bacterial and nerve cell
communication
A second part of CBN’s project focuses on membrane functions
when cells take up material from their surroundings (endocytosis),
resulting in the formation of new intracellular vesicles, and when
cells liberate material to their surroundings (exocytosis), resulting
in the fusion of intracellular vesicles with the cell membrane. These
processes are involved both in the release of neurotransmitters by
nerve cells as well as in cell-to-cell signaling in bacteria. By use of
advanced nanoscale methods, including new superresolution
microscopic techniques, it is the aim both to study and to regulate
membrane fusion- and fission- processes with the goal of generating new principles for medical intervention. Moreover, based on
the insights obtained, it is the goal to investigate the basic properties and toxic effects of native and artificial vesicles with the purpose of designing novel membrane nanocontainers for drug delivery.
"Taken together, we are convinced that our efforts over the next
five years will lead not only to enhanced understanding of signal
transmission across biological membranes but also provide new
strategies for diagnostics and treatment of brain disorders and
infectious diseases”, concludes Dimitrios Stamou.
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S RESEARCH PRIZES
the lundbeck foundation’s research prizes
Since 1987, the Lundbeck Foundation has awarded research prizes
to honor and encourage outstanding researchers in biomedicine
and natural sciences and thus draw attention to the significance of
research for society.
Candidates are proposed by senior researchers at the Danish
research institutions following calls for nomination and the
Research Prize Committee selects the recipient in conjunction
with external evaluators.
The largest and oldest prize is the Lundbeck Foundation’s Nordic
Research Prize, which today is DKK 2 million of which DKK
600,000 is a personal prize, and DKK 1.4 million to research of
the prize recipient’s choosing.
Several of the talent prize recipients are young Danish researchers
who – as part of their education – have worked at a foreign
research institution. The award has also been granted to young
foreign researchers who at the time of the award conducted their
research at a Danish research institution.
This prize was founded in 1987 under the name the P.V. Petersen
Prize and was established in respect of H. Lundbeck's former
Research Director Poul Viggo Petersen, who became the first
recipient of the prize.
Since 1987, the prize has been awarded to 24 researchers including
15 from the Danish research institutions, 4 from Swedish research
institutions, 3 from Norwegian and 2 from Finnish research institutes. The prize is an honorary prize, for which nominations cannot be
submitted. In selecting candidates for the prize the Lundbeck Foundation’s Research Prize Committee consults with leading scientists,
including previous recipients, and seeks international assessment of
the candidates proposed as the basis for awarding the prize.
the lundbeck foundation research prize
for young scientists
In 2001, the Lundbeck Foundation established a research prize for
young researchers under the age of 40. The Foundation calls for
nominations for the prize and candidates are suggested by senior
researchers at Danish research institutions. The recipient is selected
by the Lundbeck Foundation Research Prize Committee in conjunction with external evaluators. The prize is a personal prize of
DKK 300,000 and the recipient must be conducting research at a
Danish research institution at the time of the award.
the lundbeck foundation talent prizes
Upon the establishment of the prize for Young Scientists, The
Foundation’s Research Prize Committee noted a large number of
nominated young researchers under the age of 30 who had already
made a remarkable research contribution. In 2001, the Board of
Trustees decided to award three prizes for particularly talented
young scientists. The prize is a personal prize of DKK 100,000
and the recipient must be conducting research at a Danish research
institution at the time of the award.
Each year the Lundbeck Foundation receives many qualified
suggestions for candidates to the Lundbeck Foundation prizes for
young researchers and talents, and the Foundation is pleased to
note that there is a good growth layer in Danish research.
major new prize in 2011
The Lundbeck Foundation's Board of Trustees has decided to
establish a major European prize within brain research to be
called Grete Lundbeck European Brain Research Prize – The Brain
Prize. This prize is dedicated to honor outstanding European brain
researchers and to enhance the interaction between Danish and
European brain research e.g. by prize recipients participating in
research exchange programs with Danish research institutions,
chairing symposiums and the like. The prize will be awarded for
the first time in 2011.
To strengthen the new prize’s outreach activities to promote
interaction between Danish and other European brain research,
the Lundbeck Foundation has decided to seek to establish a separate prize foundation: "Grete Lundbeck European Brain Research
Foundation" with an independent board and administration, and
an internationally composed review committee. The board members will include the rectors of the universities of Copenhagen,
Aarhus and Southern Denmark. The foundation and the price are
named after Grete Lundbeck, who in 1954 had the foresight to
establish the Lundbeck Foundation, and thereby made it possible
to provide substantial support for Danish research.
Following the establishment of the new European prize the
Lundbeck Foundation's Board of Trustees has decided to cease the
awarding of the Nordic Research Prize. The recipient for 2010,
Professor Jes Olesen from Glostrup Hospital, thus becomes the last
recipient of this award.
the 24 recipients of the lundbeck foundation’s nordic prize
for outstanding research
Professor, M.D. Jes Olesen 2010
Professor, M.D. Lars Farde
1999
Professor, Ph.D. Mart Saarma
2009
Professor, M.D. Thue W. Schwartz
1998
Professor, M.D. Niels E. Skakkebæk 2008
Professor, Dr. Phil. Peter E. Nielsen
1997
Professor, M.D. Dr. h.c. Anders Björklund 2007
Professor, M.D. Per Andersen
1996
Professor, M.D. D.M.Sc. Jens F. Rehfeld
2006
Professor, M.D., D.M.Sc., Dr. h.c. Arvid Carlsson
1995
Professor, Ph.D. Ole Petter Ottersen
2005
Professor, Chief Physician, M.D., Dr. h.c. Niels A. Lassen
1994
Professor, Ph.D. Jon Storm-Mathisen
2005
Professor, M.D. Carl-Gerhard Gottfries
1993
Professor, Ph.D. Matthias Mann
2004
Professor, M.D. Lars-Inge Larsson
1991
Professor, M.D. Olaf Paulson
2003
Professor, M.D., D.M.Sc., Dr. h.c. Erik Strömgren
1990
Professor, M.D., Ph.D. Kari Alitalo
2002
Professor, D.Pharm. Povl Krogsgaard-Larsen
1989
Professor, M.D. Keld Danø
2001
Professor, M.D., Dr. h.c. Mogens Schou
1988
Professor, Dr. Phil. Karl Anker Jørgensen
2000
Director, Civil Eng. P.V. Petersen
1987
2010
2003
2009
2004
2008
2005
2007
1997
1991
2006
1996
1990
2005
1995
2002
2001
1994
1993
1989
1988
2000
1999
1998
1987
31
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION’S NORDIC RESEARCH PRIZE 2010
the classification, epidemiology
and cost of migraine
jes olesen, professor of neurology
32
THE LUNDBECK FOUNDATION'S RESEARCH PRIZES
The Lundbeck Foundation’s Nordic Research Prize is an honorary prize that is given for outstanding research in scientific
areas that the Foundation supports. In 2010 the prize was awarded Professor, M.D. Jes Olesen in recognition of his seminal
and comprehensive contributions to clinical headache research.
Migraine is a disease characterized by attacks of severe headache,
and increased sensitivity to light and sound. When no preceding
symptoms are present it is called migraine without aura and when
the headache is preceded by visual or other neurological symptoms
it is called migraine with aura. Patients are often debilitated and
must stay in bed. It is very important to identify the mechanisms
underlying the disease in order to be able to develop better treatments. This has been the most important part of the research of Jes
Olesen and his group. This article focuses on the impacts on public
health expenditure of migraine.
classification and diagnosis
In order to know how frequent a disorder is, it must be possible to
diagnose it accurately throughout the world. That became possible
in 1988 when the International Classification of Headache Disorders was prepared with Jes Olesen as anchorman. It placed all headache disorders in a logical hierarchy and provided precise criteria
for all the different diagnoses. Subsequently, this classification has
been updated and adopted by the World Health Organization
(WHO). The classification of the different types of migraine is
shown in table 1 and the diagnostic criteria for migraine without
aura in table 2.
how frequent is migraine?
Within the last year, 10 per cent of the Danish population have
had one or more migraine attacks and 16 per cent have had
migraine at least once in their life. Overall, there seems to be only
small differences in these numbers between countries, between
highly and less highly developed societies and between rural and
urban environments. Asians may suffer less from migraine than
Africans and Caucasians, but it cannot be ruled out that the reporting of frequencies has been influenced by cultural issues.
Most patients relatively rarely have attacks, but two per cent of the
population has two or more monthly attacks that may last up to
three days. Furthermore, those affected by migraine are also more
often disposed for other ailments (so called co-morbidity) such as
depressions, anxiety, allergies and metabolic disorders. An increased
frequency of strokes has been seen in younger women with migraine, particularly if they suffer from migraine with aura. New
Danish and international population studies indicate that migraine
becomes more and more frequent, but the reason for this has not
yet been determined. Increasing our knowledge of the reason for
this change is of the utmost importance if we are to avoid a
“migraine epidemic”.
the costs of headache disorders
The Global Burden of Disease study by the WHO measured the
disability caused by all diseases throughout the world using DALYs
(Disability Adjusted Life Years), a time-based measure that combines years of life lost due to premature mortality and years of life
lost due to time lived in states of less than full health. Migraine was
in the top 20 list and for women it was number 12, reflecting
increased frequency and severity in females. A Danish study
showed that one out of six days of sickness absence per year or 17
per cent of all absenteeism was caused by migraine or other headaches. The advent of better medicine for the actual migraine-attacks
has not yet reduced this figure, and development of better prophylactic treatments are crucial to reduce the impact of migraine on
general health.
In the extensive study “Cost of Disorders of the Brain in Europe”,
the financial cost of 12 major brain disorders was measured in 27
countries. The total cost of migraine in the EU (450 million inhabitants) was 27.000 million Euros per annum. One of the highest
costs was absenteeism from work (figure 1). In comparison to other
brain disorders, migraine came after dementia but was more costly
than epilepsy, movement disorders or multiple sclerosis (figure 2).
The latter disorders, however, had a higher proportion of direct
cost. According to Danish studies, non-migraine headaches are at
least as costly as migraine. In an ongoing European study, the previous cost analysis is updated and extended to comprise six more
disorders. Thereby the inclusion of non-migraine headache types is
likely to bring the cost of headache disorders above 50.000 million
Euros per annum, which equals the costs to society of dementia.
conclusions
We now have clear definitions of migraine and other types of headaches, including detailed descriptions of their epidemiology and
their costs to society. For 35 years, Danish migraine research has
been characterized by a translational approach to understanding
the molecular and cellular mechanisms underlying the disease, at
the same time shedding light on the frequency, burden and cost of
the disease to patients as well as to society. This has helped bring
Danish migraine research to the international forefront, where
scientists and clinicians are increasingly focused on neurobiological
research aimed at an improved understanding of disease mechanisms, enabling the development of better drugs.
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S RESEARCH PRIZES
Table 1 / Classification of migraine
Table 2. / Diagnostic criteria for migraine without aura:
• Migraine without aura
A. At least 5 attacks fulfilling criteria B-D
• Migraine with aura
B.Headache attacks lasting 4-72 hours
• Typical aura with migraine headache
• Typical aura with non-migraine headache
• Typical aura without headache
• Familial hemiplegic migraine (FHM)
• Sporadic hemiplegic migraine
• Basilar-type migraine
• Childhood periodic syndromes that are
commonly precursors of migraine
• Cyclical vomiting
• Abdominal migraine
(untreated or unsuccessfully treated)
C.Headache has at least two of the following characteristics:
1. Unilateral location
2. Pulsating quality
3. Moderate or severe pain intensity
4. Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)
D.During headache at least one of the following:
1. Nausea and/or vomiting
• Benign paroxysmal childhood vertigo
2. Photophobia and phonophobia
• Retinal migraine
E.Not attributed to another disorder
• Complications of migraine
• Chronic migraine
• Status migrainosus
• Persistent aura without infarction
• Migrainous infarction
• Migraine-triggered seizures
• Probable migraine
• Probable migraine without aura
• Probable migraine with aura
• Probable chronic migraine
Figure 1
     
   
Figure 2
     
Million Euros
60000
Indirect costs
Direct non-medical costs
Direct healthcare costs
50000
40000
30000
20000
10000
S
M
so
n
in
rk
Pa
y
ps
ile
Ep
ke
ro
St
in
e
ra
ig
M
em
en
t
ia
0
D
Premature death 0.5%
Hospitalization 12%
Drugs 5%
Outpatient care 7%
Social services 31%
Informal care 9%
Other direct costs 5%
Sick leave 28%
Early retirement 3%
THE LUNDBECK FOUNDATION’S RESEARCH PRIZE FOR YOUNG SCIENTISTS
dna damage response –
the cell’s built-in defence against cancer
professor niels mailand
The human body consists of just under one million billion cells.
For such a complex organism to function, every cell must be part
of a social network that dictates how they behave. An important
principle in any fully developed organism is homoeostasis, i.e.
balance between how many cells die and the number of new ones
formed. As a result, strict control is exercised over cell growth, both
stemming from within the cells themselves and from their environment. Cancer occurs when a single cell eludes these control mechanisms and starts to divide in an uncontrolled manner that may lead
to the formation of a cluster of cells – a malignant tumour.
35
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S RESEARCH PRIZES
”Ever since the emergence of the simplest life forms billions
of years ago, cells have had to cope with the problem of
DNA damage. Evolution has developed and refined methods
to protect cells against the potentially lethal effects.”
The reason that cancer cells do not behave like normal cells is that
their DNA is different. Random changes in the cell’s DNA, called
mutations, can lead to the production of too much or too little of
certain proteins, or cause them to function in a damaging manner.
As the cell’s proteins are responsible for all of its processes, these
mutations can impact upon the normal process of cell division.
The vast majority of mutations are the result of DNA damage that
has not been properly repaired. In reality, cells are constantly exposed to DNA damage, both by natural processes and by unhealthy
lifestyles. Among the natural sources of DNA damage are free radicals, formed by the cell’s natural metabolism, as well as radiation
from the Sun and from outer space. In terms of lifestyle, people
expose themselves to DNA damage by, for example, smoking,
excessive sunbathing or contact with toxic chemicals.
Ever since the emergence of the simplest life forms billions of years
ago, cells have had to cope with the problem of DNA damage.
Evolution has developed and refined methods to protect cells
against the potentially lethal effects. As a result, all cells contain a
variety of proteins, the primary purpose of which is to repair DNA
damage efficiently and properly. A complex network of signaling
Figure 1
Binding of proteins to DNA damage. By firing a laser beam through the cell
nuclei, the DNA in the laser’s path is damaged. Many of the proteins in the
DNA-damage response react to the formation of these lesions by accumulating at the points in the cell nucleus where the damage has occurred.
Here are two nuclei that contain the protein 53BP1 coupled to the
0 min.
paths, collectively referred to as ‘the DNA-damage response’,
govern these proteins. In the event of DNA damage, the response
affects many aspects of cell regulation, including cell growth, cell
death and – of course – DNA repair. Cells that are in the process
of growing and dividing are particularly sensitive to DNA damage
and its consequences. Therefore, in colloquial terms, the pause
button is pressed when these cells are exposed to DNA damage,
temporarily halting their growth until the damage is repaired.
One of the main goals of Niels Mailand's research at the Danish
Cancer Society has been to understand how the DNA-damage
response functions in human cells, and therefore how it protects
us against cancer. The researchers in his group have focused on
identifying the proteins that help maintain and repair human
DNA, in order to better understand how they interact. One
important characteristic of many of these proteins is that they
accumulate in the event of DNA damage (figure 1). This causes
a higher local concentration of the factors that facilitate efficient
DNA repair. The proteins arrive extremely rapidly, and in a specific
sequence, to the DNA damages. In recent years, intensive research
into the DNA-damage response has shown that the repair proteins
green fluorescent protein (GFP), which has been hit by the laser. The two
photographs were taken before (left) and 10 minutes after the laser irradiation (right). The green line through the cell nucleus shows an accumulation
of GFP-53BP1, evidence that DNA repair is taking place.
10 min.
A focused audience learning about the details of the DNA-damage response.
Detailed insight into the molecular aspects of the DNA-damage
response is an important precondition both for understanding how
cancer arises and for improving treatment. DNA damage may lie
behind cancer, but paradoxically enough we treat most cancers
with chemo- and radiotherapy, the aim of which is to inflict so
much damage on the cancer cells’ DNA that they die. Cancer
cells are usually more sensitive to DNA damage than healthy cells
because their DNA-damage response is destroyed at an early stage
of their transformation from normal cell to cancer cell. This is why
chemo- and radiotherapy are so effective in many cases. However,
the effect of these treatments on healthy cells limits how aggressively the cancer can be treated, and the well-known side effects of
chemotherapy are caused by unintentionally killing the body’s most
sensitive healthy cells. As a result, intensive research is now being
conducted into more precisely targeting the treatment of cancer
cells, e.g. by inhibiting specific enzymes in the DNA-damage
response. RNF8, RNF168 and HERC2 are all obvious inhibitory
proteins that drugs should be developed to counteract. The rationale is that the cancer cells are already the result of a compromised
DNA-damage response, so additional interference in their already
weakened ability to repair DNA can “push them over the edge”,
while normal cells will typically have alternative defence mechanisms upon which to fall back. Future research will hopefully show
whether targeted inhibition of these and other enzymes in the
DNA-damage response is capable of forming the basis for new,
improved and less harmful cancer therapy.
Figure 2
Simplified model of how RNF8, RNF168 and HERC2 signal the presence
of DNA damage and stimulate repair of DNA. When damage occurs to
DNA, RNF8 is rapidly attracted to the spot on the DNA where the damage
has occurred (Step I). The presence of DNA damage also stimulates the
binding of RNF8 to HERC2, and together these two proteins attach a chain
of ubiquitin molecules to the chromatin in the immediate vicinity of the
damage (Step II). The ubiquitin chain serves as a binding platform for the
protein RNF168, which is also able to add ubiquitin chains to chromatin in
the event of DNA damage, and which therefore increases the amount of
ubiquitin in the vicinity of the damage. The high concentration of ubiquitin
chains in the event of DNA damage now acts as an effective binding platform for a number of DNA repair factors (depicted in grey) that are brought
into contact with the areas of DNA damage and efficiently repair them,
restoring the DNA to an intact state.
help each other to locate damage by chemically modifying one
another as well as chromatin (DNA and DNA-storage proteins in
cell nuclei). These modifications act like a glue that enables the
proteins to bind with each other in new ways and to “stick” to the
DNA damages. Amongst other things, Niels Mailand’s research has
identified three enzymes (RNF8, RNF168 and HERC2) that
chemically modify chromatin in the event of DNA damage, using
the molecule ubiquitin. This alters the chromatin structure and
forms a binding platform for a series of DNA repair proteins
(figure 2). If just one of these three enzymes is removed, the DNA
repair is compromised and the cell’s ability to survive DNA damage
is significantly reduced. The RNF8, RNF168 and HERC2 proteins
are key components of our cells’ defence against DNA damage, and
consequently potentially also against the diseases associated with
defects in the response.
DNAdamage
Chromatin
Step 1
Step 2
Step 3
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S JUNIOR GROUP LEADER FELLOWSHIPS
THE LUNDBECK FOUNDATION’S
junior group leader
fellowships
2009
”THE GOLGI NETWORK WORKS AS A
RAILWAY STATION INSIDE THE CELL.
TRAINS CONSTANTLY DEPART FROM
A RAILWAY STATION WITH DIFFERENT
DESTINATIONS. IN THE GOLGI
NETWORK, PLASMA MEMBRANE
PROTEINS ARE SORTED INTO DIFFERNT
TRANSPORT VESICLES AND THEN
TRANSPORTED TO SPECIFIC AREAS
OF THE CELL’S SURFACE.”
Lene Niemann Nejsum
38
Name:
Steen Brøndsted Nielsen
Title and age:
Associate Professor, Ph.D. from University of Copenhagen, 37 years
Field of research:
Molecular physics and photobiophysics
Research goal:
To discover the electronic properties of molecular ions and study the importance of their surrounding
environment.
What is the topic of your research?
My research seeks to describe excited molecular states – their appearance, dynamics and influence on
reaction paths. A molecule is in an excited state when one of its electrons has been elevated to a higher
energy state. Such excited states play a major role everywhere in nature, e.g. in photosynthesis. I am, for
example, interested in understanding DNA’s photophysics, i.e. the molecule’s response to light, and why DNA
is, in fact, so photostable. DNA works almost like a sun screen – it effectively converts electronic energy into
heat. My group examines in detail the electronic communication between the bases in DNA, both in its liquid
and gas phase. One goal of our research is to design a DNA strand that can be used in the future as a nanowire in molecular electronics. Peptides (short simple protein strands) are another interesting class of biomolecules. We are trying to steer the splitting of peptides in certain directions by influencing their electronic states.
We are also studying the molecule that makes fireflies emit light and metalloporphyrins, e.g. heme, which
gives blood its red colour. Our research requires detailed descriptions of the molecules’ different electronically
charged states. The environment surrounding the photoactive molecules is gradually built up experimentally
in order to identify the importance of individual water molecules or amino acids for the photoactivity of the
molecules we are investigating.
How important is co-operation with
international colleagues for your work
and your field of research?
I collaborate with more partners abroad than in Denmark, as it is inspiring and exciting to work with
researchers from around the world and learn new ways of doing things. Bringing together the best of many
research environments is ideal, and I deliberately seek to have researchers of different nationalities in my
group.
What do you expect to achieve with
the grant from the Lundbeck Foundation?
The grant makes it possible for me to stay at the forefront of my field. One thing is to build up a group, but
quite another to keep it going. I have been able to retain very talented post docs and recruit new, committed
and promising Ph.D.-students.
With advanced equipment at our disposal, such as the storage rings ELISA (gas-phase experiments) and
ASTRID (synchrotron radiation beam lines for dissolution experiments – see figure), my group has unique
working opportunities. Our ambition is also to develop new equipment for new types of experiments.
Electrostatic Ion Storage ring in Aarhus
(ELISA). Ions are stored in the ring,
and their interactions with laser light is
examined.
The research is interdiciplinary. By the use of the
instruments of physics, we address chemical and
biological problems.
PHYSICS
CHEMISTRY
ELISA
Aarhus Storage Ring in Denmark
(ASTRID) is a highly intensive lightsource. Light with wawelengths of
170-300 nm is used to study DNA.
BIOLOGY
ASTRID
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S JUNIOR GROUP LEADER FELLOWSHIPS
Name:
Troels C. Petersen
Title and age:
Associate Professor, Master of Science in physics, Ph.D. from Universite de Paris XI, 34 years
Field of research:
Particle Physics at CERN’s LHC Accelerator
Research goal:
To search for new particles and new phenomena in the data from the LHC, especially dark matter.
What is the topic of your research?
The physics research of recent years has revealed that matter as we know it (in the form of atoms) constitutes
only a tiny fraction of the Universe – less than 5%. The remainder is largely “invisible” to us and consists of
what we call dark matter and dark energy.
Dark matter appears to consist of a yet unknown types of particles. There are also theoretical reasons to
believe that other types of fundamental particles exist in addition to those we know already (e.g. electrons).
As a result, the hunt for dark matter is potentially the biggest challenge facing basic research in the natural
sciences in the 21st century.
Using CERN’s new LHC accelerator, we may be able to generate these new particles in a laboratory setting
by means of energy-rich proton collisions, and study them with advanced detectors such as ATLAS. The first
of these collisions is shown in the figure.
In the spring, LHC commenced 18 months of colliding protons at extreme speeds. The first step in the hunt
for dark matter will be based on these collisions. The daily running of the LHC accelerator is therefore the
very “pulse” of our research, and expectations of what might be found in the subsequent data analyses are
sky-high.
However, there are huge challenges to face before the results are published. For example, processing the
enormous volume of data (10,000,000 GB p.a.) will require entirely new ways of using computers and networks. Fortunately, the LHC accelerator and the ATLAS experiment are working better than most had dared
hope, and are already generating provisional results.
How have you created a career as a
researcher – did you follow a “master
plan”?
I thought about it when I started a higher education. I wanted to be a scientist, but I also knew that it was not
something you just choose to be. My plan has always been to pursue a research career as far as possible,
safe in the knowledge that a science degree would leave me with plenty of other options.
What do you expect to achieve with
your grant from the Lundbeck
Foundation?
Just being part of the ATLAS experiment and making a contribution to research in particle physics and the
mysteries of the Universe is for me a great motivation and an honour. If we also make a major discovery,
e.g. find candidates for dark matter and/or the Higgs particle (the last hypothetical particle according to the
standard model in particle physics), I will not just be extremely proud, I will also know that I added to our
knowledge of the Universe.
First collision in the ATLAS detector.
On 23 November 2009 at 14:22, two
protons from the LHC collided for the first
time in the ATLAS detector. The result
of the collision is shown here. Coloured
lines and rows of white dots indicate the
passage of charged particles through
the detector.
Name:
Lene Niemann Nejsum
Title and age:
Assistant Professor, Master of Science in Biology, Ph.D. from University of Aarhus, 35 years
Field of research:
Cell polarisation and protein sorting
Research goal:
To map how cells sort membrane proteins.
What is the topic of your research?
My research focuses on the specialised functions of epithelia, the tissues that form the body’s inner and outer
surfaces. For an epithelium to function properly, it is important that the various parts of the cells’ surfaces
(so-called plasma membrane domains) have the right mix of ion channels and transport molecules. This
requires that newly synthesised proteins are transported to the correct plasma membrane domain, and that
they are then correctly regulated in terms of their number, location and activity.
During my post doc. study visit to Professor W. James Nelson at Stanford University, we could prove that
newly synthesised proteins designed to function in the area of the epithelium cell’s membrane, which faces
away from the epithelium’s surface are sorted in the cell’s so-called Golgi network (see figure) before being
transported to the plasma membrane. My new research group at Aarhus University will study the underlying
molecular mechanism, i.e. identify the molecules responsible for this sorting, and study, with the aid of animal
models, the physiological consequences of the sorting mechanism.
The team will also study how plasma membrane channels and transport molecules are embedded and regulated in, respectively, the lateral (contact to neighbouring cell) and basal (contact to underlying tissue) plasma
membrane by using nanomaterials and specialised microscopy (total internal reflection fluorescence (TIRF)).
This research will map out completely new regulatory mechanisms for channel and transport proteins, which will
contribute to increased knowledge about diseases caused by an imbalance in the cells’ salt and water levels.
How have you built up your research
career?
To be considered for a post as group leader at the University and for a grant from the Lundbeck Foundation
Junior Group Leader Fellowship, you must have a unique research profile, a strong publication list and a research plan. You also have to have the ability and ambition to be a supervisor and administrator. I deliberately
applied for a post doc. position that was outside of my Ph.D. supervisor Professor Søren Nielsen’s (Aarhus
University) network because I wanted to improve my skills in a new field. Through my existing network, Professor W. James Nelson’s laboratory at Stanford University was recommended as a world leader in epithelium
cell polarisation research. I sent him an uninvited application, explaining why I had chosen his laboratory,
and outlined how a prolonged stay in his research group would provide me with the background, I needed to
establish an independent research career.
I had funding from Denmark which is important as it ensures a very high degree of freedom to pursue your
own research interests. After nearly five years at W. James Nelson’s laboratory, I looked into the possibilities
of joining a research environment in Denmark. I applied for the Lundbeck Foundation’s Junior Group Fellowship to join the Department of Molecular Biology at Aarhus University and now have the opportunity to start an
independent research group. I look very much forward to training and mentoring new talent.
Schematic drawing of a polarized
epithelial cell. Adherens junctions (AJ)
are localized between the apical and basolateral plasmamembrane. The apical
plasmamembrane is the surface of the
epithelium. The lateral plasmamembrane
is in contact with neighbouring cells and
the basic plasmamembrane is facing the
extracellular matrix. Newly synthesized
plasmamembrane proteins are sorted in
the Golgi network which lies as a stack
of plates over the cell's nucleus, and
are transported in small spheres called
vesicles to the plasmamembrane.
(Figure from L.N. Nejsum and W.J.
Nelson, Front. Biosci., 2009)
Apical PM
Apical PM
MT
-
MT
-
MT
-
ARE
ARE
MT
MT
Golgi
Nucleus
Golgi
Nucleus
Nucleus
BRE
Basal PM
ARE
MT
Golgi
+
Apical PM
BRE
+
ECM
Basal PM
BRE
+
ECM
Basal PM
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S JUNIOR GROUP LEADER FELLOWSHIPS
Name;
Søren Gøgsig Faarup Rasmussen
Title and age:
Master of Science in Human Biology, Ph.D. from University of Copenhagen, 40 years
Field of research:
Structural biology and molecular pharmacology
Research goal:
To achieve insight into the activation mechanism for G-protein-coupled receptors and the substrate translocation mechanism for neurotransmitter transporters.
What is the topic of your research?
It is about mapping out the links between the molecular structure of G-protein-coupled receptors and neurotransmitter transporters, and the changes in the structure that form the basis for their respective functions.
G-protein-coupled receptors act a bit like switches on the surface of the cell – they can be turned on or off
depending on the external stimuli acting upon the receptor, e.g. hormones, neurotransmitters or medicine.
When a hormone binds to its receptor, the receptor is activated (i.e. turned on) by changing from an inactive
to an active state. Via its G-proteins on the inside of the cell membrane, the cell can register activated receptors on the cell surface, triggering an internal response to external stimuli.
While I worked as a post doc. at Professor Brian Kobilka’s laboratory at Stanford University, I helped to map
out the molecular structure of a particular G-protein-coupled receptor, the beta2 adrenergic receptor, in its
inactive state using X-ray crystallography. I have subsequently worked on crystallising the same receptor in
an active state. However, the way in which the receptor changes its structure between inactive and active
states by binding medicines or natural binding partners cannot be comprehensively illustrated by crystal
structures alone.
Funding from the Lundbeck Foundation will allow my research team to map out hormone- and medicineinduced structural changes in G-protein-coupled receptors using fluorescence-spectroscopic and electronparamagnetic-resonance (EPR) techniques.
How important is collaboration with
international colleagues for your work
and your field of research?
It has been of great significance to my research and many advantages can be derived from establishing international research partnerships. In some cases, collaboration has been crucial to the feasibility of a research
project. In others, it has enhanced a manuscript’s scientific value by including the results of experiments by
one or more partners. New discoveries are frequently made during partnerships, and new ideas and opportunities emerge to develop existing projects or start new ones.
In the research fields of structural-function studies of G-protein-coupled receptors and neurotransmitter
transporters, you will often encounter international partnerships between experimentalists and theoreticians
with expertise in molecular-dynamic simulations. Sometimes, the experimentalists’ results are difficult to
publish alone, and benefit from interpretation and being underpinned by simulations. Conversely, the theorist
may need the experimentalists to test the validity of a prediction obtained by simulation.
The molecular structure of the beta2
adrenergic receptor (blue), a G—protein—
coupled receptor, in its inactive
conformation bound to the beta blocker
carazolol (orange).
”The physics research of recent
years has revealed that matter
as we know it (in the form of
atoms) constitutes only a tiny
fraction of the Universe – less
than 5%. The remainder is largely
’invisible’ to us and consists of
what we call dark matter and
dark energy.”
TROELS C. PETERSEN
43
THE LUNDBECK FOUNDATION 2009│10
THE LUNDBECK FOUNDATION'S JUNIOR GROUP LEADER FELLOWSHIPS
Name:
Martin Røssel Larsen
Title an age:
Associate professor, Master of Science, Ph.D. from University of Southern Denmark, 40 years
Field of research:
Biochemistry and Molecular Biology
Research goal:
Functional characterization of depolarization-dependent signaling pathways in nerve terminals
What is the topic of your research?
A synapse is a specialised contact where signals can be exchanged between two nerve cells. Chemical
synapses use small signaling molecules, neurotransmitters for this cell-to-cell communication between nerve
cells. They are stored in small packages termed synaptic vesicles (SVs) that are bound to the cell’s skeleton
at the nerve terminals when nerve cells are not active. Upon depolarization (i.e. when the nerve cell has been
triggered), neurotransmitters are released by the presynaptic nerve terminal into the synaptic cleft which is
the narrow space between the pre- and postsynaptic cells (i.e. the nerve cell sending the signal and the cell
receiving the signal), where they bind and activate specific receptors at the post-synaptic membrane which
then pass on the signal in the cell-to-cell communication (see figure for overview). This overall process is
called synaptic transmission. The release of neurotransmitters is triggered by the influx of calcium ions
through ion-channels in the presynaptic membrane. An increase of calcium ions in the presynaptic nerve
terminal leads to a multitude of molecular events including neurotransmitter biosynthesis, filling of the SVs
with neurotransmitter, transportation of the SVs to the plasma membrane and eventually release of neurotransmitters. Most of these events are controlled by addition or removal of phosphate molecules at synaptic
proteins (phosphorylation and dephosphorylation) by specialized enzymes, activated when a nerve cell is
triggered. The ultimate aim of the project is to obtain a comprehensive knowledge of the phosphorylation
mediated mechanisms involved in synaptic transmission, which automatically will lead to an understanding
of several neurological diseases, such as epilepsy. This knowledge could lead to the development of new
pharmacological targets and drugs for a number of severe neurological diseases.
In my group we have previously developed a number of specific and sensitive strategies for the identification
and characterization of phosphorylated proteins from biological samples, strategies that are now widely used
by researchers in the field of phosphoproteomics. We will use these strategies in combination with standard
molecular cell biological methods to characterize phosphorylation sites in synaptic proteins which are important for the different molecular mechanisms underlying synaptic transmission.
How important is collaboration with
international colleagues for your
work?
Simplified overview of calcium signaling
in nerve terminals.
One important aspect in research that I have experienced myself is the international perspective, the interaction and collaboration with internationally recognized scientists and exposure to other cultures. I started my
research career in a large Danish research group in which 1/3 of the researchers were from other countries.
This meant that I became aware of a large number of new techniques and new ideas derived from challenging discussions with senior scientists who had a broad and in many cases more diverse knowledge. The
present project will be performed in close collaboration with Prof. Phillip J. Robinson at the Children’s Medical
Research Institute in Sydney, Australia, with whom I have had a long and fruitful collaboration. Using the
synergistic interaction between our two groups, we have characterized various proteins in synapses after
nerve cell triggering. Via meetings and visiting student internships, our two groups will act as training facilities
for each other. This opportunity to perform international research is a very big inspiration for our young
scientists and students.
lfi a s - the lundbeck foundation’s
commercial activities
The funding activities are carried out by the Foundation itself but
are financed to a significant degree by the dividends the Foundation receives from its wholly owned investment and holding company, LFI a/s, which manages the commercial activities. LFI a/s
owns controlling interests in the two listed companies H. Lundbeck A/S and ALK-Abelló A/S. In addition to this, the majority
of the portfolio investments, which amount to approx. DKK 12
billion, are held by LFI a/s. In 2009, the activities of LFI a/s were
expanded. At the beginning of the year, LFI a/s acquired a 28%
ownership interest in the listed biotech company LifeCycle Pharma
A/S as well as a number of unlisted biotech funds from H. Lundbeck A/S. Based on these assets, the establishment of a life science
investment function was initiated in LFI a/s.
At the end of 2009, LFI a/s established a real estate investment
company jointly with C.W. Obel Ejendomme A/S with a view
to investing in commercial property located centrally in both
Copenhagen and Aarhus. This company, Obel-LFI Ejendomme
A/S, is managed by C.W. Obel Ejendomme A/S.
H. Lundbeck A/S, of which the Lundbeck Foundation owns 70%
of the share capital through LFI a/s, is a leading global pharmaceutical company which focuses on the development and marketing
of medicines for the treatment of diseases of the central nervous
system. The company employs a staff of approx. 5900, 1500 of
whom are involved in research and development.
2009 was a good year for H. Lundbeck A/S from a financial point
of view. Turnover increased by 19% to DKK 13,747 million and
the financial result increased by 21% to DKK 2,007 million. The
increase was driven by growth in all regions, growth in the main
products Cipralex/Lexapro, Ebixa and Azilect, and the acquisition
of American Ovation Pharmaceuticals Inc, which today is called
Lundbeck Inc. The company, which was acquired in March 2009,
has provided H. Lundbeck A/S with, among other things, a platform in the USA and access to two newly launched products,
Xenazine and Sabril, both for the treatment of severely crippling
diseases of the central nervous system.
H. Lundbeck A/S also invested considerable funds in research and
development in 2009, and the company has several new product
candidates in the pipeline which potentially can be ready to be
launched within the next five years and help the replacement of
the turnover from the products whose patents will expire in the
coming years. Unfortunately, Lundbeck also experienced in 2009
a delay in the development of Lu AA21004, which is currently in
phase III, for the treatment of depression. This contributed to the
fall in the company’s share price in 2009 by 13.9% in spite of a
generally positive development on the equity market.
ALK-Abelló A/S is a global market leader in the development and
marketing of drugs for allergy vaccination. Through LFI a/s, the
Lundbeck Foundation owns 38% of the company’s capital and
has 66% of the votes. ALK-Abelló A/S has 1500 employees and,
in 2009, invested DKK 349 million in research and development.
The profit for the year increased from DKK 95 million in 2008
to DKK 118 million in 2009. The increase in operating profit
(EBIT) amounted to 47%. Continued investments in research and
development reduced the increase in the net result. ALK-Abelló
A/S’ American partner, Merck, successfully completed two clinical
studies on the company’s new, tablet-based product Grazax. As a
result, registration will be applied for and it is expected that this
tablet will be subsequently launched in North America. Grazax
is now approved in 13 European countries as eligibile for subsidy,
partly based on long-term studies which have shown a significant
sustained effect after the end of treatment.
other investments
In 2009, the portfolio investments, which constitute the available
funds of the Foundation and LFI a/s, provided a return of 14.3%,
amounting to DKK 1.5 billion. Subsequently, the available funds
amount to DKK 12,091 million compared to DKK 10,834 million at the end of 2008 and DKK 12,177 million at the end of
2007. Thus, the losses in 2008, a financially unusual year, were
regained in 2009. All investment classes gave a positive return in
2009. Returns of 32% on equity holdings, 6.7% on Danish
bonds and 31% on corporate bonds were recorded. The return
on property amounted to 22%. At the end of 2009, the portfolio
activities were distributed as follows: 31% in equity holdings,
66% in bonds and the money market and 3% in real estate.
life science investments
LFI a/s’ new investment entity, LFI Life Science Investments, made
its first investment at the end of 2009. The investment was in
EpiTherapeutics, which is a relatively new Danish company with
world-leading skills in epigenetics and the use thereof for, in particular, the development of new drugs for the treatment of cancer.
THE LUNDBECK FOUNDATION 2009│10
LFI A/S – THE LUNDBECK FOUNDATION'S COMMERCIAL ACTIVITIES
Epigenetics entails chemical changes in the molecules that regulate
gene expression, thus determining whether a gene is expressed or
not.
LifeCycle Pharma A/S also expects a negative result in 2010.
Initiatives have been launched to ensure that the use of the company’s resources is prioritised more effectively.
Since its foundation, LFI Life Scince Investments has received
many requests for investsments and, during the course of 2010, the
entity is expected to make further investments. The strategy of LFI
Life Science Investment is primarily to invest in European projects
and companies with projects ready for actual product development.
However, individual investments will be made in newly started
companies if the conditions are right. This also enables interaction
between the Foundation’s grantmaking activities and the investment opportunities generated by the universities based on their
research.
outlook for 2010
LFI a/s’ associate, LifeCycle Pharma A/S, is based on a patented
formulation technology, MeltDose, which has proven able to
improve absorption and bioaccessibility of both approved and new
medicines. Based on this technology, the company has set up a
pipeline of clinical projects and, in 2009, covered considerable cost
of clinical trials, in particular for a product for immunosuppression
in connection with organ transplants. This is the background for
the negative annual result of DKK 270 million. LFI a/s’ share of
this loss, amounting to DKK 76 million, was charged to the profit
and loss account under the result for participating interest.
   
H. Lundbeck A/S 49%
ALK-Abelló A/S 6%
Portfolio
investments 45%
The Lundbeck Foundation expects to distribute grants of approx.
DKK 340 million in 2010, of which DKK 100 million will be
used to 7 fellowships for Research Leaders who wish to start up
a research group of high international calibre at a Danish research
institution. The Foundation does not anticipate establishing of
new Centres of Excellence in 2010.
The Foundation’s financial result will depend on the commercial
activities in H. Lundbeck A/S and ALK-Abelló A/S and the return
on the portfolio investments. Further information about the outlook for the two listed subsidiaries’ expectations is available at
www.lundbeck.com and www.alk-abello.com.
    
Danish bonds 47%
Corporate bonds 7%
Cash and
cash eqvivalents 12%
Equity holdings 26%
Private equity 3%
Life Science 2%
Real estate 3%
management and corporate governance
The Lundbeck Foundation is managed by a Board of Trustees consisting of six members elected among themselves and three members
elected by employees of the two companies, H. Lundbeck A/S and ALK-Abelló A/S. The board appoints the Foundation's managing
director.
The Board members are elected among themselves and are self-supplementing. Election takes place at the annual meeting. The members
of the board, who are elected by the employees of the two companies, cannot participate in the election.
Members of the Board are elected for one year, i.e. for the period until the end of the next annual meeting. Re-election can take place.
However, election or re-election of someone who has been a member of the board for more than a total of 12 years or has turned 75 years
cannot take place. The rule in the previous sentence can be dispensed of under special circumstances.
The Board of Trustees reconstitutes itself after each annual meeting through the election of its chairman and vice-chairman.
LFI a/s has the same board and managing director as the Foundation. The chairman of the Foundation's Board of Trustees is also chairman of LFI a/s' board but, if it is deemed practical, there may be different vice-chairmen on the two boards.
The Lundbeck Foundation (and LFI a/s) holds a minimum of four board meetings a year, plus a two-day seminar to discuss strategy, etc.
The board also visits the Foundation's research centres and attends contact meetings with Danish universities where the Foundation has
interests.
There are written rules addressing potential conflicts of interest in relation to grant-making, as well as rules governing Trustees' and others'
use of these allocations.
The Board of Trustees subjects itself to continuous evaluation in dialogue with the chairman and individual board members, followed
by discussions among the board as a whole. The Foundation aims to hold an "arm's length" relationship to the board of directors of
H. Lundbeck A/S and ALK-Abelló A/S. These two boards, at any given time, must comprise a majority of members, normally including
the chairman, who are independent of the Foundation. The Foundation's policy regarding its relationship to these companies remains
unchanged: that two board members from each company also serve on Foundation's Board of Trustees, that the Foundation's board
chairman is not a member of either of the companies' board of directors, and that the Foundation's board members who also serve on the
companies' boards normally do not serve as a chairmen, but can serve as vice-chairmen.
The Foundation's Board of Trustees does not interfere with the companies' daily operations, but considers it important that the companies
have qualified and effective boards of directors that can support the development of the companies to the benefit of shareholders.
The Lundbeck Foundation (and LFI a/s), its Board of Trustees and members of management only trade stock in H. Lundbeck A/S and
ALK-Abelló A/S in special periods designated by the companies' boards of directors in connection with announcements to the stock
market.
47
THE LUNDBECK FOUNDATION 2009│10
RESULTS 2009
summary of financial statement
for the foundation 2009
DKK mio.
Share of results of H. Lundbeck A/S, ALK-Abelló A/S and LCP
Investment income from LFI a/s
Operating costs in LFI a/s
1,169
1,334
-15
commercial profit
2,488
Investment income in the Lundbeck Foundation
Operating in the Lundbeck Foundation
non-commercial profit
155
Income before tax
Tax
2,643
-4
Result for the year before grants
2,639
6,837
9,522
16,359
2,224
27
359
2,610
18,969
645
18,324
income statement for the year ended 31 december
2009
171
-16
net assets at 31 december 2009
Commercial investments:
Shares in H. Lundbeck A/S, ALK-Abelló A/S and LCP
Portfolio investments, etc.
Non-commercial investments:
Financial assets in the Lundbeck Foundation
Property and buildings
Receivables and cash
Total assets
Amounts granted and payables, etc.
The Lundbeck Foundation is subject to the Danish Commercial Foundations Act and the Danish Financial Statements Act, and the Foundation’s
financial statements will be submitted to the authorities together with the consolidated financial statements of the LFI Group, comprising the
wholly-owned subsidiary LFI a/s, as well as the Lundbeck Group and ALK-Abelló Group.
The above financial statements differ from the provisions of the mentioned Act as regards specifications and presentation.
The commercial shareholdings in H. Lundbeck A/S and ALK-Abelló A/S are measured at equity value, a total of DKK 6,748 mio. The total
market value of LFI a/s’ shareholding in H. Lundbeck A/S and of B shares in ALK-Abelló A/S, measured at market prices at 31 December 2009,
was DKK 14,193 mio.
THE LUNDBECK FOUNDATION 2009│10
CENTRES OF EXCELLENCES 2005-2009





 






   -
  
 
CBN – The Lundbeck Foundation Centre for Biomembranes
in Nanomedicine
Professor, M.D. Ulrik Gether
and Assoc. Professor, Ph.D. Dimitrios Stamou
LUNA – The Lundbeck Foundation Nanomedicine Centre for
Individualized Management of Tissue Damage and Regeneration
Professor, M.D. Allan Flyvbjerg
and Professor, Ph.D. Jørgen Kjems
NanoCAN – The Lundbeck Foundation Nanomedicine
Research Centre for Cancer Stem Cell Targeting Therapeutics
Professor, M.D.
Jan Mollenhauer
CINS – The Lundbeck Foundation Centre for Clinical
Intervention and Neuropsychiatric Schizophrenia Research
Professor, M.D.
Birte Glenthøj
Fast-Track – The Lundbeck Foundation Centre for
Fast-Track Pain and Risk Free Hip and Knee Arthroplasty
Professor, M.D. Henrik Kehlet
and Professor, M.D. Kjeld Søballe
CIRRO – The Lundbeck Foundation Centre
for Interventional Research in Radiation Oncology
Professor, M.D. Jens Overgaard
and Professor, M.D. Cai Grau
LUCAMP – The Lundbeck Foundation Centre for Applied
Medical Genomics in Personalized Disease Prediction
Professor, M.D.
Oluf Borbye Pedersen
COPSAC – The Lundbeck Foundation Centre
for Copenhagen Studies on Asthma in Childhood
Professor, M.D.
Hans Bisgaard
CETAME – The Lundbeck Foundation Centre
for Translational Medicine
Professor, M.D.
Torben F. Ørntoft
LCTC – The Lundbeck Foundation Centre
for Theoretical Chemistry
Professor, Dr.Phil.
Poul Jørgensen
LTC – The Lundbeck Foundation Theoretical Centre
for Quantum System Research
Professor, Ph.D.
Klaus Mølmer
CAMD – The Lundbeck Foundation Centre
for Atomic-scale Materials Design
Professor, Ph.D.
Jens K. Nørskov
MIND – The Lundbeck Foundation Centre
for Membrane-receptors in Neuronal Disease
Professor, Ph.D. Anders Nykjær and
Professor, M.D. Claus Munck Petersen
CIMBI – The Lundbeck Foundation Centre
for Integrated Molecular Brain Imaging
Professor, M.D.
Gitte Moos Knudsen
LUCENS – The Lundbeck Foundation Centre
for Neurovascular Signaling
Professor, M.D.
Jes Olesen
The Foundation’s support of scientific activities comprises specific scientific projects, Junior Group Leader Fellowships and
centres of excellence within biomedical and natural sciences.
The list below shows the Foundation’s centres of excellence 2005-2009. You can read more about the centres established in
2009 in this publication.
 
  
 
. 

Communication between nerve cells and signaling
between bacteria
DKK 34 million
in the period 2010-2015
10 senior researchers
and 15 Ph.D. students
The mechanisms behind the imbalance between tissue damage
and tissue regeneration in disease
DKK 30 million
in the period 2010 – 2015
26 senior researchers
and 10 Ph.D. students
Targeted treatment of cancer stem cells
using nano carriers
DKK 35 million
in the period 2010 - 2015
4 senior researchers
and 7 Ph.D. students
Research into tools for use in individualised
schizophrenia treatment
DKK 30 million
in the period 2009-2014
7 senior researchers
and 9 Ph.D. students
Quicker recovery through optimised
surgical intervention
DKK 35 million
in the period 2009-2014
2 senior researchers
and 10 Ph.D. students
Research into better radiotherapy for the benefit
of cancer patients
DKK 30 million
in the period 2009-2014
47 senior researchers
and 30 Ph.D. students
The influence of genes on arteriosclerosis –
possible methods for preventing lifestyle diseases
DKK 60 million
in the period 2008-2013
60 senior researchers
and Ph.D. students
The centre studies the impact of the interaction between
heredity, lifestyle and environment on development of asthma
DKK 20 million
in the period 2008-2013
5 senior researchers
and 4 Ph.D. students
Molecular diagnostic and bioinformatic risk calculation
of common cancers
DKK 20 million
in the period 2008-2013
5 senior researchers
and 2 Ph.D. students
Interpretation of macroscopic measurements
on a molecular basis
DKK 20 million
in the period 2007-2012
9 senior researchers
and 10 Ph.D. students
Studies of atoms and their interaction
with light
DKK 20 million
in the period 2007-2012
17 senior researchers
and 16 Ph.D. students
Developing theories of how a material can be structured
atom by atom to achieve certain properties
DKK 25 million
in the period 2007-2012
26 senior researchers
and 19 Ph.D. students
Multidisciplinary basic research into molecular
cell functions
DKK 50 million
in the period 2006-2011
24 senior researchers
and 15 Ph.D. students
Studies of factors in the brain that increase the risk of developing
brain disorders, including depression and memory disturbance
DKK 40 million
in the period 2006-2011
35 senior researchers
and 15 Ph.D. students
Research into the role of blood vessels
in brain disorders
DKK 30 million
in the period 2006-2011
12 senior researchers
and 18 Ph.D. students

 
- 
 +    
 +    
@.
..
MORTEN ALHEDE┃LEKTOR PH.D. TINE ALKJÆR ERIKSEN┃VIDENSKABELIG ASSISTENT CAND.SCIENT.
GE PH.D. IBEN BACHE┃LEKTOR PH.D. LASSE KRISTOFFER BAK┃ADJUNKT CAND.SCIENT. STEFANIA G
ONDE┃ADJUNKT PH.D. CHARLOTTE MENNÉ BONEFELD┃POST DOC. PH.D. JONAS BORCH┃PROFESSO
ADJUNKT CAND.SCIENT. MARCO CHIARANDINI┃ADJUNKT PH.D. BIRGITTE MØNSTER CHRISTENSEN┃L
SCIENT. BRIAN DELLA VALLE┃PH.D.-STUDERENDE CAND.SCIENT. THI AI DIEP┃POST DOC. PH.D. CHRIST
GEROD┃POST DOC. CAND.SCIENT. VERA EHRENSTEIN┃LEKTOR LIC.SCIENT. HANS EIBERG┃ADJUNK
ENE FAUSTRUP┃PH.D.- STUDERENDE CAND.SCIENT. MUSTAFA FAZLI┃KLINIKCHEF DR.MED. ULLA FELD
TIR┃PH.D. CAND.SCIENT. MADS T. FRANDSEN┃LEKTOR PH.D. BENTE FRØLUND┃PROFESSOR DR.MED
DR.MED. ULRIK GETHER┃LEKTOR DR.PHIL. MARCUS THOMAS PIUS GILBERT┃AFDELINGSLÆGE DR.ME
D. JENS PETER GØTZE┃RESEARCH SCHOLAR CAND.POLYT. JANUS A. J. HAAGENSEN┃ASSOCIATE PRO
ANSEN┃RESEARCH ASSISTANT PH.D. LINDA HARKNESS┃LEKTOR PH.D. RASMUS HARTMANN-PETERS
LTH┃PROFESSOR PH.D. ELSE KAY HOFFMANN┃LEKTOR PH.D. HANS JÜRGEN HOFFMANN┃LEKTOR D
YLDIG┃LEKTOR PH.D. ALBERTO IMPARATO┃POST DOC. CAND.SCIENT. ADIBA ISA┃POST DOC. PH.D. J
ØGH JENSEN┃KLINISK ASSISTENT CAND.MED. MORTEN KVISTHOLM JENSEN┃PROFESSOR PH.D. NIEL
DR.MED. ARNE LUND JØRGENSEN┃POST DOC. PH.D. CHARLOTTE GRUBE JØRGENSEN┃PH.D.-STUDE
AN KELLY┃PROFESSOR DR.MED. LARS VEDEL KESSING┃DR.MED. JØRGEN KIELER┃POST DOC. PH.D
DR.MED. KLAUS KROGH┃SENIOR RESEARCHER PH.D. RON KUPERS┃AFDELINGSLÆGE PH.D. OLE HYL
CHE┃ADJUNKT CAND.SCIENT. JACEK LICHOTA┃POST DOC. PH.D. HANNA SOFIA LINDGREN┃POST DO
NANNA MACAULAY┃LÆGE PH.D. KIRSTEN MADSEN┃GROUP LEADER PH.D. NIELS MAILAND┃PH.D.-S
KAMILLA MISKOWIAK┃POST DOC. PH.D. BRIAN MOLDT┃PROFESSOR DR.SCIENT. JAN MOLLENHAUER
N┃PH.D.-STUDERENDE CAND.SCIENT. JAKOB VENNIKE NIELSEN┃PH.D.-STUDERENDE CAND.SCIENT. J
SSOR DR.MED. BØRGE GRØNNE NORDESTGAARD┃PROFESSOR DR.MED. JENS RANDEL NYENGAARD
.D. RIKKE KATRINE JENTOFT OLSEN┃ADJUNKT PROFESSOR DR.MED. SJURDUR FRODI OLSEN┃SENIO
ARIA PAULSSON┃PH.D.-STUDERENDE CAND.SCIENT. NIS BORBYE PEDERSEN┃POST DOC. PH.D. RASM
CÉSAR DA SILVA PINHEIRO┃LEKTOR PH.D. JEPPE PRÆTORIUS┃MOLEKYLÆRBIOLOG PH.D. KIRSTEN
PH.D. ADAM ANDERS EDVIN ROTH┃LÆGE PH.D. MORTEN RUHWALD┃LEKTOR PH.D. MARTIN RØSSEL
TSLEV┃PROFESSOR DR.MED. ULF SIMONSEN┃PH.D.-STUDERENDE STUD.MED. TORJUS SKAJAA┃KLIN
R PH.D. CHARLOTTE SUETTA┃PROFESSOR PH.D. INGE MARIE SVANE┃PH.D.-STUDERENDE CAND.SCIE
OMMERUP┃PH.D.-STUDERENDE CAND.MED. FRANCESCO TREPICCIONE┃KLINISK LEKTOR PH.D. NIELS
D. LARS LINDHARDT VINDELØV┃PROFESSOR DR.MED. JOHN VISSING┃LEKTOR PH.D. THOMAS VOSEG
CHAEL WINTERDAHL┃PROFESSOR PH.D. JØRGEN F.P. WOJTASZEWSKI┃LEKTOR PH.D. DAVID P.D. WO
ED. NIELS FEENTVED ØDUM┃POST DOC. PH.D. AMANDA RODRIGUES AMORIM ADEGBOYE┃PH.D.-STU
E ARLETH┃SYGEPLEJEDIREKTØR MARGIT ASSER┃SENIORFORSKER OG LABORATORIELEDER PH.D.
OR DR.MED. HANS BISGAARD┃DIREKTØR MIKKEL BOHM┃PROFESSOR DR.SCIENT. MIKAEL BOLS┃ST
LEKTOR PH.D. STEEN BRØNDSTED NIELSEN┃LEKTOR PH.D. LENNART BUNCH┃PROFESSOR DR.MED.
JOHN COUCHMAN┃PH.D.-STUDERENDE CAND.SCIENT. JACOB FLYVHOLM CRAMER┃PH.D.-STUDEREN
NT. LINE DRUBE┃PH.D.-STUDERENDE CAND.SCIENT. KRISTINA B. V. DØSSING┃LEKTOR CAND.SCIENT.
RENDE CAND.SCIENT. TILDE ESKILDSEN┃STUD.SCIENT. KELECHI EZEKWE┃LÆGE PH.D.-STUDERENDE
.MED. ANE BÆRENT FISKER┃STUD.MED. EMIL LOLDRUP FOSBØL┃PROFESSOR DR.MED. ALLAN FLYV
LIC.SCIENT. MICHAEL GAJHEDE┃LEDENDE OVERLÆGE DR.MED. STEEN GAMMELTOFT┃SENIORFORS
ØNTVED┃ASSOCIATE PROFESSOR PH.D. THOMAS GÜNTHER POMORSKI┃POST DOC. PH.D. SØREN GØ
D.-STUDERENDE CAND.SCIENT. JONAS TIND HANSEN┃GRUPPELEDER PH.D. KLAUS HANSEN┃LEKTOR
HAY-SCHMIDT┃LEKTOR PH.D. YLVA HELLSTEN┃UDVIKLINGSCHEF KIM GLADSTONE HERLEV┃POST DO
POST DOC. PH.D. CHRISTIAN ANSGAR HUNDAHL┃PH.D.-STUDERENDE CAND.SCIENT. LARS GRØNDAH
N┃PROFESSOR DR.MED. BOYE LAGERBON JENSEN┃POST DOC. PH.D. JAN KRISTIAN JENSEN┃LEKTO
PH.D. TERRY LYNNE JERNIGAN┃PROFESSOR DR.MED. BENTE JESPERSEN┃PRODUCER PH.D. ANDERS

Similar documents