CIR Annual report 2010

Transcription

Annual Report
2010
Centre for
Immune Regulation (CIR)
Ce
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IR
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Vision statement
This centre identifies and
investigates novel mechanisms of
immune dysregulation to advance
the development of therapeutics
Key accomplishments 2010
• Generated an Ig double knock-in mouse with an anti-Id BCR and established that
Id-specific T and B cells can recognise Id+Ig via conventional mechanisms for T-B
collaboration.
• Developed a method to isolate, clone and express antibodies from single antigen
specific plasma cells of small intestinal biopsies, which is now harnessed to isolate and
characterise TG2-specific plasma cells of coeliac lesions.
• Optimised production of functional soluble T-cell receptors in E. coli, which allows
for high throughput screening of many T-cell receptor variants following molecular
engineering.
• Identified that the chemokine receptor CCR3 and its ligand CCL28 are involved in organspecific T-cell homing to the upper airway mucosa.
• Unraveled a mechanism by which ubiquitination influences the turnover of MHC class
II in model cells and dendritic cells.
Invariant-chain enlarged endosomes (pseudo colored). Photo: Frode M. Skjeldal.
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Director´s comments
Ludvig M. Sollid
Centre Director
The biggest event for CIR in 2010, I suppose, was the
declaration of CIR as a FOCIS (Federation of Clinical
Immunology Societies) Centre of Excellence. This status
came after thorough evaluation of an application we
submitted nearly a year in advance. The status provides
an opportunity for CIR to strengthen its translational
immunology activities and to further build an
interdisciplinary translational immunology community.
The membership of the FOCIS Centers of Excellence
community will offer us an effective training environment
for translational researchers. It will also give us new,
valuable links to other similar centres of excellence
around the world.
Another big event for CIR in 2010 was the move of
Inger Sandlie’s group from the Blindern campus to the
Department of Immunology at Rikshospitalet. This has
undoubtedly led to intensified interaction between Inger’s
people and other researchers at CIR.
A third important event for CIR in 2010 was the retreat.
We held this at Dr Holms Hotel at Geilo in April. This
allowed us to combine science with skiing activities.
Both the Scientific Advisory Board and the Board of CIR
attended. The scientific program was of very high quality.
In addition to numerous presentations by centre members,
there were lectures by the Scientific Advisory Board
member Søren Buus, as well as by Nils Christian Stenseth
(Centre for Ecological and Evolutionary Synthesis,
another CoE at the University of Oslo) and William Agace
(Lund University). The lectures were very inspiring. I also
remember the buzzing discussion in front of posters at 10
pm in the evening. I think the enthusiasm present here
is a key to the success of CIR. In 2011 we will have the
retreat in September at Sundvolden Hotel. Hopefully the
change of season and environment will spur enthusiastic
interactions yet again.
In 2010 Stine Bergholtz served as the administrative
coordinator for the first half year. Due to family reasons
she left for the US in August and luckily, Anders Sandvik,
who previously has helped CIR with administrative service
accepted the position as the administrative coordinator.
Anders did a fantastic job editing and writing the midterm evaluation report which was due 1st of December.
Without you, Anders, CIR would have been in a tight spot
– Thank you!
All of our first five Visiting Professors accepted the
invitation to revisit CIR. In 2010 we had revisits from
Jacques Neefjes (Netherlands Cancer Institute) in March,
Mark Shlomchik (Yale University) in May and Richard
Blumberg (Harvard Medical School) in September. Maria
Rescigno (European Institute of Oncology, Milan) should
have been here in October. Her visit has been postponed
one year, and Kai Wucherpfennig (Harvard Medical
School) will also come in 2011. In conjunction with the
visits of Richard Blumberg and Mark Shlomchik, we
arranged mini-symposia on antigen presentation and on
B cells in health and disease, respectively. These were
successful with the participation of lecturers from both
outside and inside CIR. I and the rest of CIR are very proud
of our Visiting Professor program. I take this opportunity
to thank the three Visiting Professors who spent time
in Oslo in 2010 for sharing their immense insight and
knowledge with us.
We have a postdoc committee at CIR who is hosting a
seminar series. In 2010 they have done a wonderful job
and invited a row of eminent speakers; Mats Bemark,
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Hedda Wardemann, Andrea Cerutti, Patrick Holt and
Frederic Geissmann. I am hoping to see additional top
international scientists holding lectures for CIR as well as
the broader immunological community of Oslo in 2011.
There were five disputations at CIR in 2010; Jorunn
Stamnaes, Ulrike Jüse, Siri Dørum, Ingvild Heier and
Eirik H. Halvorsen who all completed their PhDs during
the year. I thank the opponents for their effort in
evaluating the work of our candidates and for making the
disputations memorable events.
I will also take the opportunity to thank Alexandre
Corthay and Ranveig Braathen for arranging the journal
club of CIR. I do not know too much about the interior
life of this club as I and the rest of professors at CIR are
not allowed admission. This exclusion of the professors
is to facilitate the active participation and performance
of junior CIR members. From rumours I pick up in the
corridor, this is indeed a good journal club with a lot of
active discussions.
As I have already mentioned, the preparation for the
midterm evaluation has been an absorbing task for CIR
and its members in 2010. Part of the midterm evaluation
process was to make a project plan for CIR for 2012-2017.
This plan has the same overall goals as the plan for the
first five years, but in contrast to the proposal for the
first period, this plan rather focuses on immunological
themes and the work packages cuts across groups and
technologies. I think it is a good plan and I sincerely
hope that we will be given the trust to implement it.
The midterm evaluation report from the expert panel,
which we have already seen, suggests that we will get
a favourable evaluation and that we indeed will get this
opportunity.
Proliferating epithelial cells in the colon of a health mouse (Green, Ki67 stain; Blue, Hoechst nuclear
stain). Photo: Anders Sandvik.
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Index
Vision statement 2
Key accomplishments 2010 2
Director´s comments 3
Scientific currency 6
Patents and industrialisation 8
Core competency10
Sandlie group12
Sollid group14
Bogen group16
Johansen-Jahnsen group18
Bakke group20
Visiting Professor program22
Minisymposia24
Guest lectures25
Internal activities26
Education and career progression27
Gender equality program27
Management and boards28
Appendices29
Appendix 1. CIR staff and students29
Appendix 2. Publications35
Appendix 3. Presentations given outside CIR38
Appendix 4. Media coverage43
Appendix 5. Collaboration44
Appendix 6. Funding and expenditures46
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Scientific currency
Papers
Books and book chapters
During 2010 CIR published 41 papers in international
peer-reviewed journals, and has already by the end of
March 2011 25 papers published or in press. In general
the quality and visibility of publications from the centre
is high. Of the papers published in 2010, thirteen have an
impact factor above 5.0 and one of these has an impact
above 20.0. CIR scientists have extensive collaborations
with national and international research groups. 21 of
the papers published in 2010 with CIR authors are the
result of collaboration with international institutions.
Overall, 67% of CIR publications have an international
co-author (including internationals at CIR). Impact factor
distribution and publications based on collaborations
is illustrated in the figures below. A complete list of
publications is given in appendix 2.
CIR members contributed to ten books or book chapters
(published and in press). A complete list of books and
book chapters is given in appendix 2.
Impact factor distribution - CIR publications 2010
2% (n=1)
30% (n=12)
68% (n=28)
<5
5 - 15
>15
CIR publications with collaborating institutions 2010
24% (n=10)
24% (n=10)
15% (n=6)
37% (n=15)
CIR-only
National
International and national
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International
Patents
The accumulated number of patents granted or patent
applications filed by CIR scientists since CIR commenced
operations is 10. A complete list of patents and filed
applications is given in appendix 2.
Talks and posters
CIR members gave 39 talks as invited speakers at
international meetings in 2010. In addition 7 oral
presentations and 17 posters were presented by CIR
scientists at international conferences. A complete list of
talks and posters presented at international meetings is
given in appendix 3.
Dissemination of results to relevant
target audiences and the public
CIR members gave 32 lectures and presentations and
published 2 articles aimed at a targeted audience outside
the centre. These include postgraduate lectures, research
seminars, training courses at universities and hospitals,
as well as presentations to patient organisations, health
professional organisations and at public conventions.
CIR scientists also contributed to disseminating basic
knowledge of immunology and current research to
the general public through talks at the annual Day
of Immunology, radio programs and school visits. A
complete list of dissemination activities aimed at a
targeted audience and the public is given in appendix 3.
Media coverage
The centre, centre scientists and results emanating from
CIR appeared in printed media on 7 occasions in 2010,
including public newspapers and internal papers at the
University of Oslo, and centre scientists have appeared
once on national television. A complete list of media
coverage is given in appendix 4.
Prises and awards
Centre Director Ludvig M. Sollid was awarded the
Rank Prize for Nutrition in recognition of his work on
the mechanism of coeliac disease (www.rankprize.
org). PhD student Ingebjørg Skrindo was awarded the
Klosterstiftelsens research award for her work on the
mechanisms of airway allergy. The 2010 Department
of Molecular Biosciences Innovation Prize was awarded
to Deputy Director Inger Sandlie and postdoc Jan Terje
Andersen for their work on the interaction between
albumin variants and the neonatal Fc receptor (FcRn)
that paves the way for development of novel drugs with
improved pharmacokinetic properties. In 2010, Sollid
received a prestigious ERC Advanced Grant for a project
called “Coeliac disease: Understanding how a foreign
protein drives autoantibody formation”.
Rank Prize prizegiving at the Royal College of Physicians,
London. Ian Taylor MBE MP, Rank Prize for Nutrition recipients
Prof. Frits Koning and Prof Ludvig M. Sollid, and Lord
Selbourn. Photo: Rankprize.org.
Contribution to local research
environment
CIR aims at contributing to the immunological research
environment in Oslo by financially and scientifically
supporting the Norwegian Society for Immunology (NSI).
CIR members are collectively members of the NSI and the
centre co-hosts lectures with the society. Importantly,
guest lectures, minisymposia and workshops hosted by
CIR are open to anyone interested and we actively invite
the broader immunology community to attend these
events. Furthermore, we invite immunologists outside
the centre as speakers at these open events.
Centre staff is involved in the education of basic scientists
and clinicians at all levels. CIR scientists have organised
or lectured at graduate courses in molecular cell biology
and immunology as well as at national and international
training courses and lectures in advanced imaging.
FOCIS-CoE
In 2010 CIR became a Federation of Clinical Immunology
Societies (FOCIS) Centre of Excellence (FCE) (www.
focisnet.org). The application to become a FCE was
thoroughly evaluated and the centre management is
pleased and proud to have become a member of this
exclusive community of institutions of outstanding
clinical and scientific quality. There are 64 FCEs world
wide with 40 centres in the US and 20 in Europe. The
recent FCE status represents an international recognition
of the quality and impact of CIR and provides an
opportunity for CIR to strengthen our translational
immunology activities.
The FCE community work to facilitate innovation in
investigation and clinical practice and to raise the
awareness for clinical immunology at academic medical
institutions. CIR members have now access to FOCIS
training programs for students, research fellows and
physicians and CIR has financially supported young
scientists attending the FOCIS Advanced Course in Basic
and Clinical Immunology. As a European FCE, CIR has
been invited to participate in the European Cooperation
in Science and Technology (COST) action “European
Network for Transnational Immunology Research
and Education (ENTIRE): From Immunomonitoring to
Personalized Immunotherapy”. The Centre Director has
represented CIR at a COST-ENTIRE meeting in 2010.
”The Federation of Clinical Immunology Societies (FOCIS) Centers
of Excellence (FCE) network creates a community of researchers
and clinicians that provides an effective translational training
environment by promoting interdisciplinary innovation. www.
focisnet.org”
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Patents and industrialisation
Vaccibody AS
Two of the CIR groups (Bogen and Sandlie) have developed
novel vaccine molecules, known as Vaccibodies, which
induce superior immune responses in a variety of test
systems in animal experiments. A spinout company,
Vaccibody AS, was founded in 2007 based on a patent
application (WO2004/0253238), and the patent portfolio
was strengthened in 2010 towards clinical applications
(WO2010/61358513, EP10167291.3). The company develops
subunit vaccines and expects Vaccibodies to enter clinical
trials within the next 5 years.
The Vaccibody structure tolerates a range of antigens
and targeting modules, making it a versatile platform
technology. The molecule has the ability to target antigen
presenting cells for efficient delivery of antigen and
induction of immune responses. The vaccine is delivered
as DNA plasmids to muscle or skin, in conjunction with
electroporation that enhances uptake into cells. Such
transfected cells produce and secrete vaccibody proteins
that target antigen presenting cells and load them with
antigen for presentation to lymphocytes. Ongoing
studies focus on application of vaccibodies to cancer (B
cell lymphomas, prostate cancer), infections (influenza,
HIV, tuberculosis) or both (HPV). Bjarne Bogen and Inger
Sandlie serve on the company’s scientific advisory panel.
Part of the research activities of the company, funded in
part by the Research Council of Norway, takes place in
Bjarne Bogen’s lab according to a contract between Oslo
University Hospital-Rikshospitalet and Vaccibody AS.
Nextera AS
Phage display is the dominating technology in basic
and applied protein discovery and for development of
novel protein based diagnostics and therapeutics. A
new phage display platform, named Signal sequence
independent phage (SSIP) display, which performs better
in affinity selection than conventional methods, was
invented by Geir Åge Løset while working in the Sandlie
group. A spinout company, Nextera AS, was founded
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in 2009, based on a proprietary phage display platform
(W02009/024591A1 and WO2010/097411A1). Moreover, the
company holds the rights to the recombinant HLA class
II on phage technology (Phagemers, US provisional pending
and GB1002730.8) as well as a modified display method
through DeltaPhage (undisclosed PCT application), both
licensed through the technology transfer office at the
University of Oslo, Inven2.
Nextera AS focuses on drug target discovery within
autoimmune diseases using the Phagemer technology and
SSIP display. Inger Sandlie serves as a scientific advisor
for the company. In 2010, the company raised both public
and private funding through Innovation Norway and Birk
Venture, respectively.
Extending in vivo half-life of small drugs
The efficacy of chemical drugs, peptides, small proteins
and engineered antibody fragments are hampered by
short serum half-life, ranging from minutes to a few hours.
Therefore, strategies to tailor their serum persistence and
bio distribution are needed. Inger Sandlie and postdoc
Jan Terje Andersen have developed a unique technology
that may extend the in vivo half-life of potentially all
small drugs. This will ultimately result in better drugs,
more favourable dosing regimes and improved patient
compliance. Together with the technology transfer office
at the University of Oslo, Inven2, they have signed an
agreement with Novozymes Biopharma. So far, two
patents have been filed.
Stopping autoimmunity before it strikes
Autoimmune diseases such as lupus, multiple sclerosis,
rheumatoid arthritis and diabetes are caused when the
immune system attacks the body’s own cells. Normally,
immune cells are prevented from attacking normal cells;
however, in patients with autoimmune disease, this
“tolerance” is lost. The immediate causes of autoimmune
diseases remain unknown, partially due to the inability
to detect disease before the onset of symptoms. Early
detection of autoimmune disease is critical for assessing
new treatments. The molecule NF-kB is activated by
inflammation, which plays a key role in autoimmune
disease development, making NF-kB a prime candidate to
track autoimmune activity. Researchers at the University
of Oslo led by Ludvig Munthe and Bjarne Bogen in
collaboration with Rune Blomhoff engineered cells such
that they would emit light when NF-kB was activated. In
a mouse model of systemic autoimmunity with features
of lupus, they found that NF-kB activation signals were
present in affected organs several weeks before the clinical
manifestations of disease. The bioluminescence intensity
correlated with disease progression. NF-kB tracking
may therefore provide a new tool in the evaluation of
early autoimmune therapies. A patent application (US
provisional, US 61/262,968) has been filed by Birkeland
innovation (now Inven2).
A complete list of patents and filed applications is given
in appendix 2
Photo: Øystein H. Horgmo, Medical Photography Section, UiO/OUS.
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Core competency
Core competency at CIR
• A wide variety of cellular and humoral immune assays.
• Advanced methods in molecular biology, proteomics and cellular imaging.
• Disease models in humans and animals. The models are used to understand the molecular
mechanisms of immune regulation and autoimmunity.
• Transgenic mouse models.
• Functional characterisation of immune cells in human tissue.
• Study of immune molecules and their intracellular functions in antigen presenting cells.
• Molecular engineering for the development of new therapeutic agents and research reagents.
T cell
T cell
IL-2
IL-2
IL-1
IL-1
IL-17
IL-17
Vaccibody
IL-4
IL-4
IL-6
cell
Plasma
cell
IL-6
INF
INF
AnƟgens
Vaccibody
CH3
CH3
CH3
CH3
soluble TCR
soluble TCR
AnƟgens
FcRn-IgG
FcRn-IgG
gluten
Bogen group
Bogen group
antibodies/
auto antibodies
antibodies/
auto antibodies
Sollid
grou
Sollidp
Plasmagroup
gluten
Sandlie group
Sandlie group
Sollid group
Sollid group
Johansen group
Johansen-Jahnsen
Johansen group group
Endosome
Endosome
Bakke group
Bakke group
Epithelial
cell
Epithelial
cell
Nucleus
AnƟgen presenƟng cell
MIIC
AnƟgen presenƟng cell
MIIC
ER
ER
Nucleus
Lamina propria
Lamina propria
CIR in a cell: Research focus of the five groups in CIR. The Bakke group focus on intracellular trafficking pathways of immune
molecules involved in MHC II antigen presentation. The Bogen group develop new antigen targeting strategies for T-cell activation
with the vaccibody technology. The Sandlie group study IgG-FcR interactions and create soluble T-cell receptors (TCR) as reagents
for specific detection of MHC II-peptide complexes on the surface of antigen presenting cells. The Sollid group characterise MHC II,
gluten peptides and gluten specific T cells in coeliac disease patients and study antibody producing plasma cells and autoantibodies
in coeliac disease. The Johansen-Jahnsen group work on mechanisms of allergy development and on microbiota - host interactions
with focus on how innate and adaptive immune responses cooperate at the mucosal surface. Illustration: Tone F. Gregers.
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Bogen group
•
•
•
•
Cellular immunology
Experimental studies in mice
Transgenic mice
Recombinant Ig vaccine design
Johansen-Jahnsen group
• Human model of airway allergy in
vitro and in vivo
• Mucosal antibody system
• Dendritic cells
• Immunohistochemistry
• Flow cytometry
Sollid group
•
•
•
•
•
Human cellular immunology
In vitro study of CD4+ T cells
Recombinant soluble HLA molecules
Mass Spectrometry and proteomics
Characterisation of lymphocyte
antigen receptors
Bakke group
• Live cell Imaging
• Confocal microscopy
• Characterisation of intracellular
trafficking pathways
• Transfection of cells and the study
of binding kinetics of cytosolic
molecules
Sandlie group
• Structure and ligand binding
properties of antibodies and T-cell
receptors
• Phage display
• Recombinant molecule expression
and purification
• Interaction studies
CIR is associated with the host and partner organisations the University of Oslo and the Oslo University Hospital. The
centre consists of five research groups with different scientific expertise. The Sandlie and Bakke groups are affiliated
with the Department of Molecular Biosciences (IMBV) at the Faculty of Mathematics and Natural Sciences. The Sandlie
group moved from Blindern campus to the Department of Immunology at Oslo University Hospital-Rikshospitalet in
2010. The Bogen and Sollid groups are affiliated with the Department of Immunology and the Johansen-Jahnsen group
is a member of the Laboratory for Immunohistochemistry and Immunopathology, Department of Pathology, at the
Faculty of Medicine.
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Sandlie group
Achievements in 2010
• Characterised a recombinant albumin variant, identical to one found in a patient with very low albumin
serum levels, and showed that it does not bind the receptor that regulates serum half life of IgG and
albumin.
• Made fusion molecules of soluble T-cell receptors and IgG, and used them to detect specific antigen
presentation in the Bogen mouse model.
• Optimised production of functional soluble T-cell receptors in E.coli, which allows for high throughput
screening of many T-cell receptor variants following molecular engineering.
Ambitions for 2011
• Understand the interaction between the half life regulating receptor and it’s ligands at the amino acid
level and test the biodistribution of mutant ligands in animal models.
• Design improved molecular trackers for specific peptide – HLA complexes.
• Design improved molecular trackers for specific T-cell receptors.
• Dissect the molecular interaction of gluten reactive T-cell receptors with gluten peptide – HLA-DQ2
complexes.
Phagemer technology: The figure
shows an MHC class II molecule
with a bound antigenic peptide. We
have linked the two halves of the
complex, shown in blue and yellow,
with an artificial disulfide bridge
(pink shaded area). The bridge
stabilises the complex sufficiently
to allow phage display of this and
related molecules. Illustration:
Geir Åge Løset.
Overview of research in the group
The Sandlie group studies the structure and function of
antibodies and T-cell receptors, the specific detecting
molecules of the adaptive immune system. The purpose
of the work is to engineer soluble T-cell receptors,
antibodies and antibody derived molecules to be used in
therapy and as research reagents.
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We focus on two projects: A) Studies of the interaction
between Fc receptors, and in particular the neonatal
Fc receptor, with IgG subclasses and albumin. Key
questions are how ligand binding elicits antibody effector
functions of IgG subclasses and regulate serum half
life. B) Expression of soluble T-cell receptors for the
Inger Sandlie
detection of complexes between antigenic peptides and
HLA molecules, as well as peptide – HLA complexes for
detection of T-cell receptors. The focus is on engineering
to increase stability and affinity for molecules that are
characteristic of disease models in groups at CIR.
Key project summaries
Proteins in the blood stream are short lived and normally
degraded within a few hours or days, but the two most
abundant proteins, IgG and albumin, are rescued from
degradation and have half-lives of three weeks. The
rescue mechanism depends on their interaction with
the neonatal Fc receptor, FcRn. For us, it is crucial to
understand how FcRn rescues IgG and albumin, and to
study whether long half life may be transferred to other
protein therapeutics. In 2010 we characterized albumin
molecules from patients with low albumin level, and
found that they had lost the ability to bind FcRn. This
gives important guidance in the search for the FcRn
binding site on albumin. Contact has been established
with Novozymes Biopharma UK Ltd, which aims to take
new albumin variants designed by us to the market.
To ask questions regarding the nature of the antigen
presenting cell, the location and rate of peptide – HLA
assembly and the interaction of specific peptide – HLA
molecules with T cells, specific detection molecules are
needed. Soluble T-cell receptors are new tools for such
studies in health and disease. Phage display has been
instrumental for the success of antibody technology. We
have explored phage display of soluble T-cell receptors
and established a platform that supports engineering
and selection of specific T-cell receptors with improved
stability and affinity.
In 2010 we have published the successful expression of
two different soluble T-cell receptors from the mouse
model developed by the Bogen group. They have been
purified as folded and functional molecules from the
periplasm of E.coli as well as from transfected eukaryotic
cells. Regardless of stability engineering and expression as
bivalent molecules, we find that the binding strength must
be further improved to allow specific detection of normal
peptide levels. Furthermore, to detect specific receptors
on T cells, we have developed a technology where peptide
- HLA class II molecule complexes are displayed on
phage in a new high throughput “Phagemer” approach.
Proof of principle for the method has been obtained, and
patent application filed. A spin-out company, Nextera AS,
commercialises the new phage display- and Phagemer
technologies, and received private funding in 2010.
Central publications and patents in 2010
Andersen JT, Daba MB, Berntzen G, Michaelsen TE, Sandlie
I (2010). ”Cross-species binding analyses of mouse and
human neonatal Fc receptor show dramatic differences
in immunoglobulin G and albumin binding”, J Biol Chem,
285 (7), 4826-36.
Andersen JT, Daba MB, Sandlie I (2010). ”FcRn binding
properties of an abnormal truncated analbuminemic
albumin variant”, Clin Biochem, 43 (4-5), 367-72.
Jung ST, Reddy ST, Kang TH, Borrok MJ, Sandlie I, Tucker
PW, Georgiou G. (2010) “Aglycosylated IgG variants
expressed in bacteria that selectively bind FcgammaRI
potentiate tumour cell killing by monocyte-dendritic
cells”, Proc Natl Acad Sci U S A., 107(2):604-9.
Gunnarsen KS, Lunde E, Kristiansen PE, Bogen B, Sandlie
I, Løset GA (2010). ”Periplasmic expression of soluble
single chain T cell receptors is rescued by the chaperone
FkpA”, BMC Biotechnol, 10, 8.
Lunde E, Løset GA, Bogen B, Sandlie I (2010). ”Stabilizing
mutations increase secretion of functional soluble TCR-Ig
fusion proteins”, BMC Biotechnol, 10, 61.
Løset GÅ, Frigstad T, Sandlie I, Bogen B. “Disulphide bondstabilized functional soluble MHC class II heterodimers”
(US provisional, GB1002730.8).
Andersen JT and Sandlie I
(EP10174162.7, with Novozymes).
“Albumin
variants”
Andersen JT and Sandlie I “Albumin derivatives”
(EP10174164.3, with Novozymes).
13
Sollid group
• Discovered that a redox process regulates the activity of the enzyme transglutaminase 2 (TG2) (J Biol
Chem, 2010). The finding suggests that oxidation is a key factor determining the amount of active TG2
present in the extracellular environment.
• Found that TG2 is a particularly important factor for selection of gluten T-cell epitopes. The preferred
peptide substrates in a complex wheat gluten digest were identified to be predominantly peptides
previously identified as T-cell epitopes (PLoS One, 2010).
• Developed a method to isolate, clone and express antibodies from single antigen specific plasma cells of
small intestinal biopsies. Proof of concept was done with rotavirus plasma cells (J Immunol, 2010), and
the method is now harnessed to isolate and characterise TG2-specific plasma cells of coeliac lesions.
Ambitions for 2011
• Dissect the molecular interaction of gluten reactive T-cell receptors with gluten peptide – HLA-DQ2
complexes.
• Complete ongoing work on the cloning and characterisation of TG2-specific monoclonal antibodies
derived from single plasma cells.
Staining of plasma cells (red, CD138) and, T cells (green, CD3) and epithelium (blue, cytokeratin) in the small
intestinal mucosa of a patient with active coeliac disease (left) and a normal control (right). Note that there is a
remarkable increase in the number of plasma cells in the coeliac lesion. Photo: Ann-Christin Røberg Beitnes.
14
Ludvig M. Sollid
Our group is trying to dissect the interplay of environmental
factors and genetic factors in of chronic autoimmune
disorders. We are concentrating on coeliac disease as a
model to understand the molecular mechanisms leading
to chronic inflammatory disease. In particular, we focus
on how certain variants of HLA molecules predispose to
disease development. Over the years, we have generated
a large panel of CD4+ T-cell lines and clones cultured
from intestinal biopsy specimens from coeliac disease
patients. Characterisation of what and how these T cells
recognise gluten protein, the dietary antigen precipitating
coeliac disease, has lead to many interesting findings
such as the importance of protein structure on antigen
processing, how enzyme mediated post-translational
protein modification increases antigenicity and how HLA
binding specificity and peptide-MHC stability influence
T-cell priming. This knowledge does not only impact the
understanding of coeliac disease pathogenesis, but also
reveal general principles of immune regulation that are
applicable to other disease models. In recent times we
have taken up an interest in trying to understand the
auto-antibody response of coeliac disease. In 2010, Ludvig
M. Sollid was the recipient of an ERC Advanced Grant on
this research activity.
Coeliac disease demonstrates strong association with
particular alleles within the human leukocyte antigen
(HLA) complex, particularly HLA-DQ2 and HLA-DQ8.
These HLA-DQ molecules are directly involved in the
pathogenesis of coeliac disease by binding and presenting
gluten peptides, fragments of wheat proteins, to diseasespecific T cells in coeliac patient intestines. Presence of
IgA and IgG antibodies specific for the auto-antigen TG2 is
another specific feature of active coeliac disease. TG2 is an
enzyme that catalyses either transamidation resulting in
cross-linking of two peptides, or deamidation of glutamine
residues to glutamate in polypetides. Conspicuously, TG2
is not only the target for auto-antibodies in coeliac disease,
but it is also important for creation of antigenic gluten
T-cell epitopes. TG2-mediated deamidation introduces
negative charges to gluten peptides, thereby increasing
their binding to HLA-DQ2 and HLA-DQ8.
Currently our group is trying to understand how disease
specific auto-antibodies to TG2 are generated, and why
auto-antibody production in an individual is dependent on
HLA-DQ2 expression as well as dietary gluten exposure.
Central publications in 2010
Amundsen SS, Rundberg J, Adamovic S, Gudjónsdóttir
AH, Ascher H, Ek J, Nilsson S, Lie BA, Naluai AT, Sollid
LM (2010). “Four novel coeliac disease regions replicated
in an association study of a Swedish-Norwegian family
cohort”, Genes Immun, 11 (1), 79-86.
Bodd M, Ráki M, Tollefsen S, Fallang LE, Bergseng E,
Lundin KE, Sollid LM (2010). ”HLA-DQ2-restricted glutenreactive T cells produce IL-21 but not IL-17 or IL-22”,
Mucosal Immunol, 3 (6), 594-601.
Di Niro R, Mesin L, Raki M, Zheng NY, Lund-Johansen F,
Lundin KE, Charpilienne A, Poncet D, Wilson PC, Sollid
LM (2010). “Rapid generation of rotavirus-specific human
monoclonal antibodies from small-intestinal mucosa”, J
Immunol, 185 (9), 5377-83.
Dørum S, Arntzen M, Qiao SW, Holm A, Koehler CJ,
Thiede B, Sollid LM, Fleckenstein B (2010). “The preferred
substrates for transglutaminase 2 in a complex wheat
gluten digest are peptide fragments harboring celiac
disease T-cell epitopes”, PLoS ONE 5(11).
Gil-Humanes J, Pistón F, Tollefsen S, Sollid LM, Barro F
(2010). “Effective shutdown in the expression of celiac
disease-related wheat gliadin T-cell epitopes by RNA
interference”, Proc Natl Acad Sci U S A, 107 (39), 17023-8.
Stamnaes J, Pinkas DM, Fleckenstein B, Khosla C, Sollid
LM (2010). ”Redox regulation of transglutaminase 2
activity”, J Biol Chem, 285 (33), 25402-9.
15
Bogen group
• Established that Id-specific T and B cells can recognise Id+Ig via conventional mechanisms for T-B
collaboration.
• Expressed soluble TCR molecules in bacteria and in fusion with Ig molecules in eukaryotic cells.
• Defined a targeting unit (human MIP-1a) that can be used in vaccibodies intended for human use.
• Established an Ig double knock-in mouse with an anti-Id BCR.
Ambitions for 2011
• To describe novel mechanisms for receptor-mediated interactions between lymphocytes that may
cause autoimmune disease and tumour development.
• To explore the mechanism by which CD4+ T cells reject tumour cells.
• To further develop and translate into the clinic novel vaccine molecules for cancer and infectious
diseases.
B cell - B cell hand shake. Snarf labelled Id+A20 cells (red) with a Id+ B
cell receptor (BCR) form BCR mediated conjugates with the CMAC labelled
Idiotypic counterpart Anti-Id A20 (blue). Conjugate formation induces
apoptosis (annexin stain; green). Photo: Johanne T. Jacobsen.
16
Bjarne Bogen
The Bogen group runs projects within three areas, 1)
Idiotype-driven T-B collaboration and its role in health
and disease, 2) Novel vaccine molecules for cancer and
infectious diseases, 3) The mechanism by which CD+ T
cells can reject cancer cells. These three research topics,
for which key summaries are given below, may at first
glance seem separate but are in fact closely related. The
common theme is immunoglobulins and how these may be
recognised by T cells. Further, parts of immunoglobulins
are used as modules for the group’s development of novel
vaccine molecules.
Vaccine development. Key accomplishments in 2010 have
been to extend application of Vaccibody molecules to
influenza, HIV and tuberculosis. In 2011 we will continue
these studies and also try to develop more potent versions
of the molecules. We will also try to develop vaccine
molecules for human application.
Central publications and patents in 2010
Idiotype-driven T-B collaboration and its pathogenic role
in elicitation of autoimmune disease and cancer. Bogen
and co-workers has over the last 25 years painstakingly
established a novel type of interaction between T and B
lymphocytes where T cells recognize Ig variable regionderived idiotypic (Id) peptides presented on the Major
Histocompatibility Class II molecules on the surface
of B cells. When the B cell receive help from such Idspecific T cells, and the B cell at the same time recognise
a self antigen with it’s B-cell receptor for antigen,
the B cell, receiving these two serrate signals, will be
activated, proliferate and differentiate. Our previous
work has shown that this mechanism may cause
immune dysregulation, autoimmunity and B lymphoma
development in mice. In 2010 we have started efforts
to extend this pathogenic mechanism to patients with
Chronic Lymphatic Leukaemia (CLL) and systemic Lupus
Erythematosus (SLE). These efforts will continue in 2011.
At the same time we are extending our studies of the basic
mechanisms by establishing new strains of transgenic
and knock-in mice.
Holmøy T, Vartdal F, Hestvik AL, Munthe L, Bogen B
(2010). ”The idiotype connection: linking infection and
multiple sclerosis”, Trends Immunol, 31 (2), 56-62.
Tumour immunology. Main accomplishment in 2010 was
the demonstration that inflammation promotes rejection
of tumour cells by CD4+ T cells (Nature Communications,
2011) .
Jacobsen JT, Lunde E, Sundvold-Gjerstad V, Munthe
LA, Bogen B (2010). ”The cellular mechanism by which
complementary Id+ and anti-Id antibodies communicate:
T cells integrated into idiotypic regulation”, Immunol Cell
Biol, 88 (5), 515-22.
Ruffini PA, Grødeland G, Fredriksen AB, Bogen B
(2010).”Human chemokine MIP1α increases efficiency of
targeted DNA fusion vaccines”, Vaccine, 29 (2), 191-9.
Pier Adelchi Ruffini, Agnete Fredriksen, Bjarne Bogen.
Homodimeric protein constructs (WO2010/61358513,
EP10167291.3).
17
The human gut harbours a microbiological community of 1014 (100 trillion) bacteria consisting of Johansen-Jahnsen group
more than a 1000 species separated from the body interior by a single layer of epithelial cells. Altered composition of the intestinal microbiota has been linked to gut inflammation as well as extraintestinal diseases such as obesity, allergy and asthma. We have shown that secretory antibodies, the main adaptive effector component reinforcing the epithelial barrier, directly influences the composition of the intestinal microbiota, and in the absence of this antibody system, innate defence functions of the epithelium are activated (Reikvam et al., PLoS ONE, inpress. Thus, there is a redundancy between adaptive immunity (secretory antibodies) and innate immunity Achievements in 2010
• Identified that CCR3 and CCL28 are involved in homing of T cells to upper airways.
(defensins etc.) to reinforce the epithelial barrier in the gut. • Showed that mucosal dendritic cells respond to TSLP and induce Th2 responses.
• Identified altered composition of commensal intestinal microbes in the absence of secretory antibodies.
Central publications in 2010 Ambitions for 2011
Karlsson MR, Johansen FE, Kahu H, Macpherson A, Brandtzaeg P (2010). ”Hypersensitivity and oral • Perform detailed functional characterisation
of antigen presenting cell subsets
isolated from the
intestinal and airway mucosa.
tolerance in the absence of a secretory immune system”, Allergy, 65 (5), 561‐70. • Functionally characterise allergen-specific T cells in the upper airways.
• Elucidate mechanisms of reciprocal communication between commensal microbiota and host innate and
Illustrasjonsbilde, plaseres som i 2009 under ”ambitions for 2011”. Er kvaliteten OK? adaptive immune systems.
Immunofluorescence staining of cryosection from nasal mucosa showing that the chemokine CCL28 involved in
homing of T cells to the upper airways is expressed on the luminal side of a blood vessel (Photo: Elena Danilova).
Figurtekst Immunofluorescence staining of cryosection from nasal mucosa showing that the chemokine CCL28 involved in homing of T cells to the upper airways is expressed on the luminal side of a blood vessel Overview of research in the group
(Photo: courtesy of Elena Danilova). We work in mucosal immunology, with a particular
emphasis on how innate and adaptive immune systems
communicate and cooperate. Our projects follow two
main lines: mechanisms of allergy development and
mechanisms of peaceful coexistence between the
enormous amount of intestinal bacteria and the host.
18
Failure of peaceful coexistence may lead to chronic
inflammatory conditions in the intestinal system, but
dysbiosis is also involved in other human conditions such
as allergy, diabetes and obesity. In these systems we use
a variety of human and animal models including allergen
provocation studies in patients.
Finn-Eirik Johansen
Frode L. Jahnsen
Thymic stromal lymphopoietin (TSLP) may control
allergic Th2 inflammatory responses through induction
of distinct activation programs in dendritic cells (DCs).
In contrast to DCs in the circulation, the majority of
DCs isolated from the nasal mucosa exhibited a high
expression level of TSLP receptor and responded
strongly following TSLP-treatment. These cells increased
significantly following topical challenge of patients with
nasal allergy. Furthermore, TSLP-activated DCs induced
allergen-specific T cell proliferation and Th2 cytokine
production when TSLP was added together with the
allergen.
It has been suggested that regulatory T cells inhibit allergic
inflammation in humans by suppressing the activation of
allergen-specific effector T cells. Whether this occurs at
the site of allergen exposure or in lymph nodes has not
been determined. We found in experimentally-induced
inflammation in allergic rhinitis patients that an early
inflammatory response was followed by accumulation of
regulatory T cells in the nasal mucosa (Skrindo et al., Clin
Exp Allergy, Epub ahead of print). Our findings are similar
to those observed in allergic airways of experimental
mice, and suggest that accumulating Treg cells may
dampen the inflammation locally in allergic upper
airway inflammation. It should be explored whether
enhancement of Treg recruitment or activity in the nasal
mucosa could be amenable to therapeutic intervention.
Lymphocyte recruitment to non-lymphoid tissues is
fundamental for immune surveillance and homeostasis.
This trafficking is controlled by adhesion molecules and
chemokine receptors on circulating lymphocytes and
their corresponding counter-receptors and ligands on
venular endothelial cells in the target tissues. We found
that the chemokine CCL28 was preferentially expressed at
a high level in the nasal mucosa, and was localised to the
luminal face of vascular endothelial cells. A large fraction
(15-40%) of CD4+ T cells in the nasal mucosa expressed
the CCL28-receptor CCR3, whereas this receptor was
undetectable on T cells in the small intestine and skin.
In the circulation, CCR3+ T cells comprised a small subset
that did not express established homing receptors to
the intestine or skin. Furthermore, depletion of CCR3+
T cells from peripheral blood significantly inhibited the
T-cell response to “upper airway-specific” bacterial and
allergenic antigens.
We have found that HLA-DQ+ antigen-presenting cells
(APCs) in normal human duodenal mucosa can be divided
into at least four main subsets with striking similarities
to those described in mice: CD163+CD11c- macrophages
(~74%), and CD11c+ cells expressing either CD163 (~7%),
CD103 (~11%) or CD1c (~13%). The markers CD103 and
CD1c were partly overlapping, whereas CD163+CD11c+
APCs appeared to be a distinct population. In the coeliac
lesion we found increased density of CD163+CD11c+
APCs whereas the density of CD103+ and CD1c+ DCs was
decreased suggesting that distinct subpopulations of
APCs in coeliac disease may exert different functions
in the pathogenesis (Beitnes et al., Scand J Immunol, in
press).
The human gut harbours a microbiological community
of 1014 (100 trillion) bacteria consisting of more than
a 1000 species separated from the body interior by a
single layer of epithelial cells. Altered composition of the
intestinal microbiota has been linked to gut inflammation
as well as extraintestinal diseases such as obesity, allergy
and asthma. We have shown that secretory antibodies,
the main adaptive effector component reinforcing the
epithelial barrier, directly influences the composition
of the intestinal microbiota, and in the absence of
this antibody system, innate defence functions of the
epithelium are activated. Thus, there is a redundancy
between adaptive immunity (secretory antibodies)
and innate immunity (defensins etc.) to reinforce the
epithelial barrier in the gut.
Karlsson MR, Johansen FE, Kahu H, Macpherson A,
Brandtzaeg P (2010). ”Hypersensitivity and oral tolerance
in the absence of a secretory immune system”, Allergy,
65 (5), 561-70.
19
Bakke group
• Demonstrated a role for ubiquitination on the turnover of MHC class II in model cells and dendritic
cells (Proc Natl Acad Sci USA, 2010).
• Characterised how Rab11 control TLR4 transport (Immunity, 2010).
• Characterised the role of invariant chain on trafficking and half life of mature MHC class II molecules
(Immunol Cell Biol, Epub ahead of print).
Ambitions for 2011
• Dissect elements of the molecular mechanisms for sorting to the intracellular antigen loading
compartment based on high throughput antigen loading screens.
• Elucidate how invariant chain modulate the endosomal pathway and the influence on other immune
molecules in this pathway (i.e. neonatal Fc receptor, MHC I, CD1).
• Characterise endosomal effector function and dynamics of antigen/MHC II transport in the invariant
chain induced endocytic pathway in the Meljuso model antigen presenting cells.
HLA-DR localise to early endosomes in monocytederived dendritic cells. HLA-DR (red) and EEA1
(green). Scale bar 20µM. Photo: Ole J.B. Landsverk.
Our group has since the early nineties aimed to understand
the endocytic pathway and how peptide loading of the MHC
class II complexes (MHC II) is regulated. A special focus for
the group is to elucidate the contribution of the invariant
chain (Ii) to the biogenesis of an antigen presenting cell
(APC) specific endocytic pathway (Landsverk et al., 2009).
20
Ii plays a vital role in MHC II assembly and intracellular
transport, but has been attributed an increasing number
of additional functions in both antigen presentation and
cell signalling. An evolutionary conserved property of Ii
is to induce the convergence, or fusion of early endocytic
vesicles, and this property may serve vital functions in
Oddmund Bakke
antigen presentation, cell signaling and beyond. The
group consists of 4 postdocs, 2 PhD students, 4 master
students and 1 technician. The Bakke group also runs the
FUGE imaging facility, NorMIC-UiO, at the University of
Oslo. This core unit is used by the CIR centre and other
groups for a wide variety of projects.
The group is focusing on the properties of the endosomal
pathway in cells in general and the adaptations to this
pathway in immune cells. The projects can be divided
into four sub themes
• Sorting and trafficking of immune molecules in model
cell lines and in dendritic cells (Landsverk et al.,
Epub ahead of print, Landsverk et al., submitted 2011;
Gregers et al., manuscript).
• Regulation of vesicular transport between the Golgi
network and the endosomal pathway (Progida et al.,
2010).
• Endosomal fusion and fission events involved in
the transport of molecules in the endosomal system
(Skjeldal et al., in revision).
• Regulation of receptor signalling by endocytic sorting
and endosomal effector kinetics in the endosomal
pathway (Haugen et al., manuscript).
Our work is primarily focused on understanding the
process of antigen uptake, processing and presentation.
These events are instrumental for the initiation and
propagation of adaptive immune responses. The endocytic
pathway common for all cells is uniquely adapted by
specific immune cells to achieve this purpose, and in order
to achieve our ultimate goals with regard to discovering
the specifics of immune cell functions we have invested
a large body of research on how the endocytic pathway
functions in general in model cell systems. We have
contributed to the current understanding of cell biological
processes in the endocytic pathway in general and our
current goal is to use this foundation to elucidate the
unique adaptations to this system in antigen-presenting
cells. This will provide the basis for better understanding
of vaccination regimes and protocols for immune therapy
of cancers, autoimmune-, and infectious diseases.
Our main strategy employs a wide array of advanced live
cell imaging technologies, supplemented by biochemistry,
immunological assays and DNA/RNA techniques. The
group collaborates in several studies within CIR, where
we provide the theoretical cell biological outlook and
essential microscopy expertise. These include:
• Uptake and sorting of transglutaminase 2 in human
dendritic cells (Jorunn Stamnaes/Ludvig Sollid).
• Uptake and sorting of vaccibodies (Inger Øynebråten/
Bjarne Bogen).
• B lymphoma cells with complementary BCRs delete
each other in vitro (Johanne Jacobsen/Bjarne Bogen).
• The FcRn:Ii interaction in antigen presentation (Jan
Terje Andersen/Inger Sandlie).
Husebye H, Aune MH, Stenvik J, Samstad E, Skjeldal F,
Halaas O, Nilsen NJ, Stenmark H, Latz E, Lien E, Mollnes TE,
Bakke O, Espevik T (2010). “The Rab11a GTPase controls
Toll-like receptor 4-induced activation of interferon
regulatory factor-3 on phagosomes”, Immunity, 33 (4),
583-96.
Walseng E, Furuta K, Bosch B, Weih KA, Matsuki Y, Bakke
O, Ishido S, Roche PA. (2010) “Ubiquitination regulates
MHC class II-peptide complex retention and degradation
in dendritic cells”, Proc Natl Acad Sci U S A , 107, 2046-70.
Progida C, Cogli L, Piro F, De Luca A, Bakke O, Bucci C
(2010). “Rab7b controls trafficking from endosomes to the
TGN”, J Cell Sci. 123 (9):1480-91.
Landsverk HB, Mora-Bermúdez F, Landsverk OJ, Hasvold
G, Naderi S, Bakke O, Ellenberg J, Collas P, Syljuåsen RG,
Küntziger T (2010). “The protein phosphatase 1 regulator
PNUTS is a new component of the DNA damage response”,
EMBO Rep, 11 (11), 868-75.
Bucci C, Bakke O, Progida C (2010). ”Rab7b and receptors
trafficking”, Commun Integr Biol, 3 (5), 401-4.
21
Visiting Professor program
Maria Rescigno
Richard Blumberg
Jacques Neefjes
Mark Shlomchik
Kai Wucherpfennig
The centre has a comprehensive international network. A very important element of CIR’s activity is
the extensive relations we have formed with our Visiting Professors. These researchers, world leading
scientists from renowned institutions, spend an intensive week at the centre. During their site visit the
Visiting Professors give lectures, perform data scrutiny, supervise students and postdocs, and provide
valuable input to the research conducted. Following their visit to CIR, the Visiting Professors continue to
interact with centre scientists and the program has resulted in fruitful collaborations, exchange of ideas
and reagents, as well as researcher mobility.
We are very pleased that the entire Visiting Professor faculty has accepted to extend their initial one-year
contracts. In 2010, Jacques Neefjes, Mark Shlomchik and Richard Blumberg had their second visits to CIR
(see below for details). Maria Rescigno from the Department of Experimental Oncology at the European
Institute of Oncology in Milan, Italy, was scheduled to revisit CIR in October, but her visit has been
postponed to September 2011. Kai Wucherpfennig from the Department of Cancer Immunology & AIDS
at the Dana-Farber Cancer Institute at Harvard Medical School in Boston, USA, is scheduled to revisit CIR
in October 2011. We are very much looking forward to Rescigno’s and Wucherpfennig’s revisits.
In the autumn of 2010, CIR nominated new members to the Visiting Professor faculty. We are very proud
to announce that John Trowsdale from the Cambridge Institute for Medical Research, University of
Cambridge, UK; Sally Ward from The University of Texas Southwestern Medical Center, Dallas, USA and
Fiona Powrie from Sir William Dunn School of Pathology and Nuffield Department of Clinical MedicineExperimental Medicine Division, University of Oxford, UK, have all accepted the invitations to become
Visiting Professors at CIR. CIR is exited about our Visiting Professor program and we are very much
looking forward to interacting with these prominent immunologists in 2011.
Jacques Neefjes
During March 2010, Jacques Neefjes visited the centre.
Neefjes works at the Division of Cell Biology at the
Netherlands Cancer Institute in Amsterdam, The
Netherlands. His work focuses on the cell biology of
MHC class I and MHC class II molecules. His group has
developed fluorescent techniques to approach single
22
cell biochemistry, and use combinations of cell biology,
chemistry and biophysics to visualise biochemical
reactions in living cells. The title of his guest lecture was
“A genome-wide multidimensional siRNA screen to reveal
pathways controlling MHC class II antigen presentation”.
Mark Shlomchik
Richard Blumberg
The centre was visited by Mark Shlomchik in May 2010.
Shlomchik works at the Department of Immunobiology
at Yale School of Medicine in New Haven, USA. The main
interest of his lab includes the regulation of auto reactive
B lymphocytes and the development of high affinity B-cell
immune responses and memory cells. Lately they have
also started looking at the mechanisms by which T cells
are activated in graft vs. host disease and the subsets of T
cells that are pathogenic. The title of his guest lecture was
“How does autoimmunity get started? Mechanistic and
therapeutic implications”. During his visit CIR organised
a minisymposium on B cells in health and disease (details
on page 24).
Richard Blumberg visited the centre in September 2010.
He is working at the Department of Medicine at Brigham
and Women’s Hospital at Harvard Medical School in
Boston, USA. His research area is mucosal immunity
and he is interested in the physiological processes that
lead to the development of inflammatory bowel disease,
the management of the luminal microbial ecology,
intestinal barrier dysfunction and allergy. The title of his
guest lecture was “Regulation of Lymphocyte Function
by Carcinoembryonic Antigen Adhesion Molecule 1:
Implications for Inflammation and Cancer”. During
his visit, CIR organized a minisymposium on antigen
presentation (details on page 24).
Visiting Professor Mark Shlomchik celebrating May 17th –
Constitution Day – in Oslo 2010. Photo: Ludvig Sollid.
Visiting Professor Richard Blumberg lecturing at the CIR
minisymposium on antigen presentation. Photo: Anders
Sandvik.
Photo: Øystein H. Horgmo, Medical Photography Section, UiO/OUS.
23
Minisymposia
Minisymposia is an important part of the outreach
activity at CIR. In conjunction with visits from our Visiting
Professors, the centre organise half-day seminars aimed
at a broader audience interested in clinical- and basic
immunology and related disciplines. We actively recruit
speakers from outside CIR to these events. In 2010 CIR
organised two open minisymposia.
B cells in health and disease
May 21st
Chair: Didrik Paus, CIR
Mark Shlomchik is a world-leading specialist on B
cells, particularly on the regulation of autoreactive B
lymphocytes and the development of high affinity B-cell
immune responses and memory cells. During Shlomchik’s
visit to CIR as a Visiting Professor, the centre organised
a minisymposium on B cells in health and disease. In
addition to Shlomchik’s main lecture, Andreas Strasser
gave a lecture, followed by three short talks by young CIR
scientists. The event was well attended and generated
stimulating discussion.
Contributors and titles:
Mark Shlomchik, Yale University School of Medicine, New
Haven, CT, USA, and Visiting Professor, CIR. “Activation
and regulation of autoreactive B cells: the myeloid
connection”
Andreas Strasser, The Walter and Eliza Hall Institute of
Medical Research, Melbourne, Australia. “The role of
apoptosis in tumour development and cancer therapy”.
Johanne Jacobsen, Institute of Immunology and CIR,
University of Oslo. “BCR handshakes: interacting cells
undergo apoptosis”.
Roberto Di Niro and Rasmus Iversen, Institute of
Immunology and CIR, University of Oslo. “Possible
mechanisms for activation of autoreactive B cells in
Celiac Disease”.
Charlotta Sandin, Institute of Immunology and CIR, Oslo
University Hospital. “Gene expression profiling of T cellinduced B lymphoma”.
24
Antigen presentation
September 17th
Chair: Inger Sandlie, CIR
Richard Blumberg is a world renowned mucosal
immunologist. He has a particular interest in the
immunobiology of the neonatal Fc receptor (FcRn) which
is responsible for the transport of IgG across the intestinal
epithelium. FcRn may play a role in the uptake of immune
complexes from mucosal surfaces, has a role in antigen
presentation and regulates responses to luminal antigens.
During Blumberg’s visit to CIR as a Visiting Professor,
the centre organised a minisymposium on antigen
presentation. In addition to Blumberg’s main lecture,
Sigbjørn Fossum and Johanna Olweus were invited to
present their work. Furthermore, two young CIR scientists
gave short talks at the minisymposium. The event was
well attended and generated stimulating discussion. The
minisymposium on antigen presentation was the basis
for an article in the journal of the Norwegian Biochemical
Society (NBS-Nytt 6/2010).
Contributors and titles:
Richard S. Blumberg, Brigham and Women’s Hospital,
Harvard Medical School, Boston, USA, and Visiting
Professor, CIR. “The immunobiology of the (not
so) neonatal Fc receptor (FcRn) for IgG in antigen
presentation”.
Gunnveig Grødeland, Institute of Immunology and CIR,
University of Oslo. “Targeted DNA vaccine protect mice
against H1N1 influenza”.
Sigbjørn Fossum, Institute of Basic Medical Sciences,
University of Oslo. “The role of APLEC receptors in
adjuvant induced arthritis”.
Johanna Olweus, Institute for Cancer Research, Oslo
University Hospital. “Manipulating dendritic cells to tease
out cancer-targeted T cells”.
Tone F. Gregers, Department of Molecular Biosciences
and CIR, University of Oslo. “An endosomal tour guided
by Invariant chain in antigen presenting cells”.
Guest lectures
A postdoc committee at CIR hosts a guest lecture seminar
series.
The 2010 committee consisted of Espen S.
Baekkevold, Gøril Berntzen, Roberto DiNiro, Charlotta
Sandin and Tone F. Gregers. In 2010 there were five
speakers in this series:
Mats Bemark visited CIR in May and gave a lecture titled
“Beyond the bone marrow - defining peripheral B cell
differentiation”. The lecture was part of the Norwegian
Society for Immunology (NSI) Immunology Happy Hour
event. Bemark is currently assistant professor and group
leader at the Mucosal Immunology and Vaccine Center
at the University of Gothenburg, Sweden. His research
focus is mainly on B lymphocyte signalling and mucosal
regulation of IgA switching.
Hedda Wardemann visited CIR in June and gave a
lecture titled “The B cell antibody repertoire in health
and disease”. Wardemann is currently a junior group
leader at the Max-Planck Institute for Infection Biology
in Berlin, Germany. Her research focus is mainly on the
development of autoantibodies as part of the normal
antibody repertoire and on the association between
antibody response to infection and autoimmunity.
Andrea Cerutti visited CIR in September and gave a
lecture titled “Class switching at the mucosal interface”.
Photo: Trygve Bergeland.
Cerutti is a professor at Mount Sinai School of Medicine,
NY, USA, and at the Catalan Institution for Research and
Advanced Studies, Barcelona, Spain. His research focus
is mainly on the regulation of mucosal and systemic
antibody production and diversification in health and
disease states, including HIV infection.
Patrick Holt visited CIR in October and gave a lecture titled
“Interactions between innate and adaptive immunity in
asthma pathogenesis: new perspectives from studies on
acute exacerbations”. Holt is Deputy Director and Head
of the Division of Cell Biology in the Telethon Institute
for Child Health Research in Perth, Australia. He has a
long-standing interest in the regulation of immunological
processes in the lungs. His research activities range from
basic aspects of dendritic-cell biology to regulation of
atopic sensitisation.
Frederic Geissmann visited CIR in November and gave a
lecture titled “Differentiation and functions of monocyte/
macrophages”. Geissmann is Head of the Centre for
Molecular & Cellular Biology of Inflammation (CMCBI)
and Professor & Arc Chair of Inflammation Biology, King’s
College London, UK. He heads a research group focusing
on the molecular and cellular basis of the functional
heterogeneity of the mononuclear phagocyte system.
Photo: Øystein H. Horgmo, Medical Photography Section,
UiO/OUS.
25
Internal activities
Project meetings
To keep the members of the centre up to date on
the research within the centre, project meetings are
organised monthly. For each meeting, one of the five
groups is responsible for presenting a project. During
2010 nine project meetings were organised. Typically,
unpublished data from one or two projects are presented.
Presentations range from discussions of technical
challenges, via preliminary data to publication ready
work. Ample time is reserved for discussion following the
presentations and discussion is encouraged. At the end of
the meeting snacks and soft drinks are served to promote
interaction and to continue the discussion in a less formal
atmosphere. The project meeting is an important event
that facilitates collaboration, idea generation and critical
discussion. Furthermore, the monthly project meeting
provides a friendly venue for junior scientists less
experienced in presenting their own work. The project
meeting is also a vital activity aiming to build centre
identity and sense of community.
CIR literature seminar for young
researchers
Burkhard Fleckenstein and Stine Bergholtz. The CIR
management is very happy that the scientific advisory
board and CIR board attended the retreat. Nils Christian
Stenseth from the Centre for Ecological and Evolutionary
Synthesis, University of Oslo, gave a Key Note lecture titled
“Plagues: Past, Present and Future”. Søren Buus from the
University of Copenhagen, and member of the scientific
advisory board, opened day-two with a lecture entitled
“Analysis of the specificity of human T cell responses.
William Agace, University of Lund, gave a talk entitled
“Intestinal Dendritic cells, retinoic acid, and their role in
the regulation of intestinal T cell responses”. In addition
to these invited speakers, CIR scientists presented their
work through 17 short talks and 40 posters. The oral
presentations were organised into five sessions; “Traffic
jam”, “Gut problems”, “Hi’tech”, “Mucosal matters”,
and “Towards therapy”. Prises for the two best poster
presentations and short talks were awarded. The program
also included structured workshops and an extended
lunch break for skiing or other leisure activities. The
event was a huge success scientifically as well as socially.
The next retreat will be at Sundvolden Hotel in September
2011.
The seminars were initiated in 2008 and master students,
PhD students as well as postdocs/young researchers are
invited. The aim is to achieve training in critical evaluation
of scientific articles as well as to stimulate students
to actively participate in scientific discussions. Eight
seminars were held in 2010. The format of the seminars
has been altered and now includes a short introduction
to the chosen topic by an invited speaker followed by
discussion of a selected paper in smaller groups. The
seminar is also open for young immunologists outside
CIR. Selected articles were from journals such as Nature,
Science and Immunity. The seminars included topics
such as: differentiation of dendritic cells; host-microbiota
interactions; T-cell differentiation and re-programming;
and Fc- receptor biology. The seminar series will continue
in 2011.
CIR annual retreat
The 2010 CIR retreat was at Dr. Holms Hotel, Geilo, in April.
All CIR members were invited to participate at this 3-day
event. The retreat was organised by Inger Øynebråten,
Gøril Berntzen, Axel Berg-Larsen, Dag Henrik Reikvam,
26
Photo: Øystein H. Horgmo, Medical Photography Section, UiO/
OUS.
Education and career progression
PhD
MSc
Training of scientists is a major activity at CIR. CIR has
the ambition to educate 35 new PhDs during the 10-year
period as a centre of excellence. Since CIR commenced
operations in December 2007, 14 students at the centre
have successfully defended their thesis, and we are in
good condition to reach the production milestone. In 2010
five PhD students defended their thesis:
During 2010 four Master of Science students graduated;
Ingvild Sørum, Vedrana Grcic, Ralf Neumann and Heidi
Cecilie Larsen Spång.
Jorunn Stamnaes, “Transglutaminases in gluten sensitive
diseases”.
Ulrike Jüse, “Exploring peptide binding to the disease
associated HLA-DQ2.5 molecule by the use of peptide
libraries”.
Siri Dørum, “Substrate specificity of transglutaminases
for gluten peptides”.
Ingvild Heier, “Studies on antigen presenting cells and T
cells in airways and skin”.
Career progression
Within CIR, eight centre members have advanced
in their careers during 2010. Shuo-Wang Qiao was
promoted to associate professor (3 year temporary
position), starting January 1st and Inger Øynebråten was
promoted from postdoc to researcher. Jorunn Stamnaes
and Siri Dørum both defended their thesis in 2010 and
have continued as postdocs in the group. Lene Støkken
Høydahl, a technician and former master student, is now
a PhD student. Following their Master of Science exams,
Vedrana Grcic and Heidi Cecilie Larsen Spång have stayed
at the centre as technicians/research assistants. Anders
Sandvik left his postdoc position to take on the position
as administrative coordinator.
Eirik H. Halvorsen, “Investigation of immune processes in
rheumatoid arthritis”.
Gender equality program
Mentoring program
At the centre and generally in molecular biomedical
research there is a high proportion of female PhD
students and postdocs, while most of the senior scientists
and group leaders are male. The CIR management
acknowledges that the loss of talented young female
scientists is unfortunate and measures have been taken to
facilitate the career progression of our female postdocs to
help in the transition from postdoc to senior researcher.
Mentoring is known to improve career satisfaction and
thereby helps to increase recruitment. CIR has continued
a mentoring program for female postdocs. At the onset
of the program, CIR had a total of 17 female postdocs,
and 10 accepted the invitation to participate. A total
of five mentors, chosen among senior faculty at the
University of Oslo, have been assigned two postdocs
each. In 2010, female postdocs at CIR were invited to a
career development seminar at Lysebu, hosted by Centre
for Molecular Biology and Neuroscience (CMBN; another
Centre of Excellence at the University of Oslo). Seven CIR
members participated at this well received event. CIR has
allocated funds to continue the gender equality program
in 2011.
Technical assistance
A female postdoc must often balance research at the
bench with family responsibilities. In 2010, two postdocs
that were on or just returning from maternity leave were
assigned full time technical assistance on their projects for
a total of 4.5 months. The postdocs applied to the program,
and each application included a project description as
well as a candidate for the job, chosen among the Master
of Science students at CIR. In the application they also
described how they would communicate with and guide
the assistant. We consider this measure to be a success
and will continue the program in 2011.
27
Management and boards
Management
CIR is affiliated with two organisations, the University of
Oslo (UiO) and Oslo University Hospital (OUS). The centre
is organised directly under the Faculty of Medicine and
the Centre Director reports to the Board, which report to
the Dean at the Faculty of Medicine. The centre is headed
by professors Ludvig M. Sollid (Director) and Inger Sandlie
(Deputy Director). The centre management is supported
by an administrative coordinator. Stine Bergholtz held
the position as administrative coordinator from January
to July 2010. When Bergholtz left CIR to follow her family
abroad, Anders Sandvik took on the position. CIR consists
of five research groups headed by professors, Ludvig M.
Sollid, Inger Sandlie, Oddmund Bakke, Bjarne Bogen and
Finn-Eirik Johansen. Sollid’s group includes the group of
Burkhard Fleckenstein/Gustavo de Souza. Fleckenstein
left CIR in November 2010 and de Souza was recruited
as a group leader to manage the proteomics facility and
projects. Johansen’s group includes the group of professor
Frode L. Jahnsen. The group leaders meet for decision
making on a regular basis. The Director has the daily
responsibility for project management, administration
and delivery.
The CIR Board
*Fossum completed his term as Dean of Research by the end
of 2010. The new Dean of Research at the Faculty of Medicine,
professor Hilde I. Nebb, is the new chair of the CIR Board.
The Scientific Advisory Board
CIR has a Scientific Advisory Board (SAB) consisting of
European world-class scientists. The SAB’s mandate is
to critically evaluate and advise on the centre’s scientific
performance and progress. The SAB met with the
management group and Board during the 2010 retreat in
April.
The Scientific Advisory Board has three members:
• Professor Søren Buus, University of Copenhagen,
Denmark.
• Professor Rikard Holmdahl, Karolinska Institutet,
Stockholm, Sweden.
• Professor Sirpa T. Jalkanen, University of Turku,
Finland.
FOCIS CoE Clinical Advisory Board and
Lay Advisory Board
The governing board of CIR has four members; two from
UiO and two from OUS. The Board is appointed by UiO
and consists of the Deans of Research at the Faculty
of Medicine and Faculty of Mathematics and Natural
Sciences as well as the Heads of the Department of
Pathology and Department of Immunology.
As a Federation of Clinical Immunology Societies (FOCIS)
Centre of Excellence (FCE), CIR has established two new
advisory boards.
• Sigbjørn Fossum (chair)*, Dean of Research, Faculty of
Medicine, UiO.
• Anders Elverhøi, Dean of Research, Faculty of
Mathematics and Natural Sciences, UiO.
• Inger Nina Farstad, Head of Department of Pathology,
OUS.
• John Torgils Vaage, Head of the Department of
Immunology, OUS.
• Head physician Knut E. Lundin (chairman,
gastroenterologist, OUS).
• Professor II Geir E. Tjønnfjord (haematologist, OUS
and UiO).
• Professor Knut Dahl-Jørgensen (paediatrician, OUS
and UiO).
The authority of the Board is to ensure that the intentions
and terms of contract described in the Centre of Excellence
agreement are fulfilled. Furthermore, the Board approves
the annual budget and ensure that centre activities are
completed as outlined in the project description and
funding plan, within the adopted time frame. The Centre
Director and administrative coordinator met with the
Board twice in 2010. The Centre Director acts as the
principle liaison between the Board and the management
group.
28
The Clinical Advisory Board is responsible for facilitating
translational research at CIR and consists of:
The Lay Advisory Board focuses on strategic development,
fundraising and community outreach and consists of:
• The Director of the Norwegian Coeliac Society.
• The Secretary General of the Norwegian Asthma and
Allergy Association.
• The Secretary General of the Norwegian Diabetes
Association.
Appendix 1
CIR staff and students
Approximately 100 persons, producing 75 person years,
are involved in research at CIR. CIR actively recruits
international talents and in 2010 staff recruited from
abroad included 7 PhD students, 9 postdocs and 3
researchers, representing 14 nationalities. Three visiting
postdocs from abroad (Henrik Toft-Hansen, Morten
Nielsen and Anita Hartog) spend more than 1 month as
guests at CIR during 2010. CIR encourages researcher
mobility and financially supports team members that do
part of their postdoctoral specialisation or thesis work
abroad. In 2010, 5 CIR members (Roberto DiNiro, Synne
Jenum, Rejoanoul Islam, Jorunn Stamnaes and Denis
Khnykin) spend more than 1 month as guests in research
groups in Europe and USA. The over all gender balance
at CIR is 40/60 with an overweight of female members
among postdocs, PhD students, master students and
technicians.
35
31
Personnel per Dec 31st 2010
30
27
25
19
20
15
13
12
10
5
5
1
0
Group leaders
Students
Postdocs
PhD students
Researchers
Administration
Technicians
Group leaders
Name
Position
Funding*
Employer*
Oddmund Bakke Professor UiO UiO
Bjarne Bogen Professor UiO/OUS UiO/OUS
Finn-Eirik Johansen Professor UiO/OUS UiO/OUS
Inger Sandlie Professor UiO UiO
Ludvig M. Sollid Professor RCN-CIR UiO/OUS
29
Research scientists
Name
Position
Funding*
Employer*
Per Brandtzaeg Professor emeritus
Espen Baekkevold Researcher HRSE OUS
Alexandre Corthay Researcher UiO-CIR UiO
Burkhard Fleckenstein1 Researcher UiO UiO
Frode L. Jahnsen Professor UiO/OUS UiO/OUS
Knut E.A. Lundin Chief physician OUS OUS
Øyvind Molberg Researcher OUS OUS
Ludvig A. Munthe Associate professor UiO
UiO
Ingrid Olsen Researcher Broad Foundation OUS
Shuo-Wang Qiao Associate professor RCN-CIR UiO
Gustavo de Souza1 Researcher UiO UiO
Keith Thompson Researcher UiO UiO
Inger Øynebråten Researcher RCN UiO
Postdocs
Name
Funding*
Employer*
Silja S. Amundsen HRSE OUS
Jan Terje Andersen RCN-CIR UiO
Elin Bergseng RCN UiO
Gøril Berntzen NCS UiO
Ranveig Braathen EU/RCN UiO
Simone Bürgler SNSF/HRSE UiO
Hege Carlsen OUS/RCN UiO/OUS
Elena Danilova RCN-CIR UiO
Roberto Di Niro UiO-CIR UiO
Siri Dørum RCN UiO
Even Fossum RCN OUS
Agnete B. Fredriksen NCS OUS
Ane Funderud HRSE OUS
Tone F. Gregers RCN UiO
Anders Holm RCN-FUGE UiO/OUS
30
Name
Funding*
Employer*
Lene E. Johannessen RCN-FUGE UiO
Denis Khnykin HRSE OUS
Gerbrand Koster RCN-FUGE UiO
Maria Helen Lexberg RCN-CIR UiO
Geir Åge Løset RCN UiO
Didrik Paus HRSE OUS
Cinzia A. M. Progida UiO-CIR UiO
Melinda Raki HRSE OUS
Ingunn B. Rasmussen NCS UiO
Charlotta Sandin NCS OUS
Anders Sandvik Biotec Pharmacon UiO
Jorunn Stamnaes RCN-CIR UiO
PhD students
Name
Funding*
Employer*
Christina Bang HRSE OUS
Ann-Christin R. Beitnes OUS OUS
Axel Berg-Larsen UiO UiO
Michael Bodd H&R OUS
Muluneh Bekele Daba UiO UiO
Asbjørn Christophersen UiO OUS
Alexander Erofeev
Terje Frigstad RCN UiO
Gunnveig Grødeland RCN UiO
Kristin Gunnarsen RCN-CIR UiO
Ole-Audun W. Haabeth HRSE OUS
Eirik H. Halvorsen 2
Ingvild Heier 2
Christina Hoffmann UiO-CIR OUS
Lene Støkken Høydahl RCN UiO
31
PhD students
Name
Funding*
Employer*
Rejoanoul (“Reza”) Islam EU UiO
Rasmus Iversen UiO UiO
Johanne Jacobsen RCN-CIR UiO
Synne Jenum RCN UiO
Ulrike Jüse 2
Ana Kucera UiO UiO
Ole J. B. Landsverk UiO UiO
Kristina B. Lorvik HRSE UiO
Guro Reinholt Melum HRSE OUS
Luka Mesin RCN-CIR UiO
Audun Os UiO UiO
Dag Henrik Reikvam NCS UiO
Tahira Riaz HRSE OUS
Anna Parente Ribes NCS UiO
Fredrik Hellem Schjesvold NCS OUS
Ingebjørg Skrindo UiO UiO
Øyvind Steinsbø UiO-CIR OUS
Astrid E. V. Tutturen UiO-EMBIO UiO
Kristine Ustgård UiO UiO
Kristin Aas-Hanssen UiO UiO
Students
Name
Study
Katrine Alfsnes Master student
Stian Foss Master student
Vedrana Grcic 3,4 Master student
Henriette C. Jodal Medical student
Saranda Kabashi Master student
Tom Ole Løvaas Medical student
32
Name
Study
Ralf Neumann 3 Master student
Nicolay Rustad Nilssen Master student
Erlend Pedersen Master student
Kine Marita Knudsen Sand Master student
Heidi C. L. Spång 3,4 Master student
Ingvild Sørum 3 Master student
Technicians
Name
Position
Funding*
Employer*
Aaste Aursjø Staff engineer UiO UiO
Hege Eliassen Secretary OUS UiO
Kathrine Hagelsteen Senior engineer UiO UiO
Linda Haugen Senior engineer UiO UiO
Peter O. Hofgaard Senior engineer UiO UiO
Marie K Johannesen Senior engineer UiO UiO
Marit Jørgensen Staff engineer HRSE OUS
Mona Lindeberg Senior engineer VB OUS
Linda Manley Staff engineer OUS UiO
Martin McAdam Technician UiO-CIR UiO
Hogne Røed Nilsen Staff engineer OUS OUS
Hilde Omholt Senior engineer NCS OUS
Bjørg Simonsen Staff engineer JDRF OUS
Sathiaruby Sivaganesh Staff engineer UiO UiO
Frode M. Skjeldal Senior engineer NCS UiO
Linda Solfjell Staff engineer OUS OUS
Maria Ekman Stensland Staff engineer HRSE UiO
Kjersti Thorvaldsen Staff engineer HRSE OUS
Elisabeth L. Vikse Staff engineer EU
UiO
33
Administration
*
Name
Position
Funding*
Employer*
Stine Bergholtz 5 Senior advisor RCN-CIR UiO
Anders Sandvik 6 Senior advisor RCN-CIR UiO
CIR - Centre for Immune Regulation
EU - European Union
JDRF - Juvenile Diabetes Research Foundation
H&R - Norwegian Foundation for Health and Rehabilitation
HRSE - South-Eastern Norway Regional Health Authority
NCS - Norwegian Cancer Society
OUS - Oslo University Hospital
RCN - Research Council of Norway
RCN-FUGE - Functional genome research program at RCN
SNSF - Swiss National Science Foundation
UiO - University of Oslo
UiO-EMBIO - Steering board for Molecular Life Sciences at UiO
VB - Vaccibody AS
Several CIR members have changed employer and funding body during 2010.
The listed funding body and employer refer to the status per December 2010.
Notes:
Fleckenstein left CIR and was replaced by de Souza in November.
2
Not employed at CIR in 2010. Defended their PhD thesis in 2010.
3
Graduated in 2010.
4
Continued at CIR as technicians after graduation.
5
Bergholtz left CIR in July.
6
Sandvik started in the position in September.
1
34
Appendix 2
Publications
Papers in scientific journals
Amundsen SS, Rundberg J, Adamovic S, Gudjónsdóttir
AH, Ascher H, Ek J, Nilsson S, Lie BA, Naluai AT, Sollid
LM (2010). “Four novel coeliac disease regions replicated
in an association study of a Swedish-Norwegian family
cohort”, Genes Immun, 11 (1), 79-86.
Andersen JT, Daba MB, Berntzen G, Michaelsen TE,
Sandlie I (2010). ”Cross-species binding analyses of
mouse and human neonatal Fc receptor show dramatic
differences in immunoglobulin G and albumin binding”,
J Biol Chem, 285 (7), 4826-36.
Andersen JT, Daba MB, Sandlie I (2010). ”FcRn binding
properties of an abnormal truncated analbuminemic
albumin variant”, Clin Biochem, 43 (4-5), 367-72.
Bodd M, Ráki M, Tollefsen S, Fallang LE, Bergseng E,
Lundin KE, Sollid LM (2010). ”HLA-DQ2-restricted
gluten-reactive T cells produce IL-21 but not IL-17 or IL22”, Mucosal Immunol, 3 (6), 594-601.
Brandtzaeg P (2010). ”The mucosal immune system and
its integration with the mammary glands”, J Pediatr, 156
(2 Suppl), S8-15.
Brandtzaeg P (2010). “Food allergy: separating the
science from the mythology”, Nat Rev Gastroenterol
Hepatol, 7 (7), 380-400.
Brandtzaeg P (2010). “Astray in irritable bowel syndrome
with regard to terminology and methodology”, Scand J
Gastroenterol, 45 (1), 124-5; author reply 125.
Brandtzaeg P (2010). “Update on mucosal
immunoglobulin A in gastrointestinal disease”, Curr
Opin Gastroenterol, 26 (6), 554-63.
Brandtzaeg P (2010). ”Function of mucosa-associated
lymphoid tissue in antibody formation”, Immunol Invest,
39 (4-5), 303-55.
Brandtzaeg P (2010). ”Homeostatic impact of indigenous
microbiota and secretory immunity”, Benef Microbes 1,
211-27.
Bucci C, Bakke O, Progida C (2010). ”Rab7b and receptors
trafficking”, Commun Integr Biol, 3 (5), 401-4.
Cogli L, Progida C, Lecci R, Bramato R, Krüttgen A, Bucci
C (2010). “CMT2B-associated Rab7 mutants inhibit
neurite outgrowth”, Acta Neuropathol 120(4):491-501.
Dhanasekaran S, Doherty TM, Kenneth J, Jahnsen
F; TB Trials Study Group (2010). “Comparison of
different standards for real-time PCR-based absolute
quantification”, J Immunol Methods 354(1-2):34-39
Di Niro R, Mesin L, Raki M, Zheng NY, Lund-Johansen
F, Lundin KE, Charpilienne A, Poncet D, Wilson PC,
Sollid LM (2010). “Rapid generation of rotavirus-specific
human monoclonal antibodies from small-intestinal
mucosa”, J Immunol, 185 (9), 5377-83.
Duc M, Johansen FE, Corthésy B (2010). “Antigen binding
to secretory immunoglobulin A results in decreased
sensitivity to intestinal proteases and increased binding
to cellular Fc receptors”, J Biol Chem, 285 (2), 953-60.
Dørum S, Arntzen M, Qiao SW, Holm A, Koehler CJ,
Thiede B, Sollid LM, Burkhard Fleckenstein (2010).
“The Preferred Substrates for Transglutaminase 2 in a
Complex Wheat Gluten Digest are Peptide Fragments
Harboring Celiac Disease T-cell Epitopes”, PLoS ONE
5(11).
Etokebe GE, Skjeldal F, Nilsen N, Rodionov D, Knezevic
J, Bulat-Kardum L, Espevik T, Bakke O, Dembic Z (2010).
“Toll-like receptor 2 (P631H) mutant impairs membrane
internalization and is a dominant negative allele”, Scand
J Immunol, 71 (5), 369-81.
Fedorcsák P, Polec A, Ráki M, Holm R, Jebsen P,
Abyholm T (2010). “Differential release of matrix
metalloproteinases and tissue inhibitors of
metalloproteinases by human granulosa-lutein cells and
ovarian leukocytes”, Endocrinology 151(3):1290-8.
Gil-Humanes J, Pistón F, Tollefsen S, Sollid LM, Barro F
(2010). “Effective shutdown in the expression of celiac
disease-related wheat gliadin T-cell epitopes by RNA
interference”, Proc Natl Acad Sci U S A, 107 (39), 17023-8.
Gunnarsen KS, Lunde E, Kristiansen PE, Bogen B, Sandlie
I, Løset GA (2010). ”Periplasmic expression of soluble
single chain T cell receptors is rescued by the chaperone
FkpA”, BMC Biotechnol, 10, 8.
Hessvik NP, Bakke SS, Fredriksson K, Boekschoten
MV, Fjørkenstad A, Koster G, Hesselink MK, Kersten
S, Kase ET, Rustan AC, and Thoresen GH (2010).
”Eicosapentaenoic acid improves metabolic switching of
human myotubes”, Journal of Lipid Research 51, 20902104.
35
Holmøy T, Vartdal F, Hestvik AL, Munthe L, Bogen B
(2010). ”The idiotype connection: linking infection and
multiple sclerosis”, Trends Immunol, 31 (2), 56-62.
Husebye H, Aune MH, Stenvik J, Samstad E, Skjeldal
F, Halaas O, Nilsen NJ, Stenmark H, Latz E, Lien E,
Mollnes TE, Bakke O, Espevik T (2010). “The Rab11a
GTPase controls Toll-like receptor 4-induced activation
of interferon regulatory factor-3 on phagosomes”,
Immunity, 33 (4), 583-96.
Jacobsen JT, Lunde E, Sundvold-Gjerstad V, Munthe LA,
Bogen B (2010). ”The cellular mechanism by which
complementary Id+ and anti-Id antibodies communicate:
T cells integrated into idiotypic regulation”, Immunol
Cell Biol, 88 (5), 515-22.
Jung ST, Reddy ST, Kang TH, Borrok MJ, Sandlie I, Tucker
PW, Georgiou G (2010). “Aglycosylated IgG variants
expressed in bacteria that selectively bind FcgammaRI
potentiate tumor cell killing by monocyte-dendritic
cells”, Proc Natl Acad Sci U S A, 107 (2), 604-9.
Jüse U, van de Wal Y, Koning F, Sollid LM, Fleckenstein
B (2010). ”Design of new high-affinity peptide ligands
for human leukocyte antigen-DQ2 using a positional
scanning peptide library”, Hum Immunol, 71 (5), 475-81.
Karlsson MR, Johansen FE, Kahu H, Macpherson
A, Brandtzaeg P (2010). ”Hypersensitivity and oral
tolerance in the absence of a secretory immune system”,
Allergy, 65 (5), 561-70.
Kuo TT, Baker K, Yoshida M, Qiao SW, Aveson VG, Lencer
WI, Blumberg RS (2010). “Neonatal Fc receptor: from
immunity to therapeutics”, J Clin Immunol, 30 (6), 77789.
Landsverk HB, Mora-Bermúdez F, Landsverk OJ, Hasvold
G, Naderi S, Bakke O, Ellenberg J, Collas P, Syljuåsen RG,
Küntziger T (2010). “The protein phosphatase 1 regulator
PNUTS is a new component of the DNA damage
response”, EMBO Rep, 11 (11), 868-75.
Lunde E, Løset GA, Bogen B, Sandlie I (2010). ”Stabilizing
mutations increase secretion of functional soluble TCR-Ig
fusion proteins”, BMC Biotechnol, 10 (1), 61.
Låg M, Rodionov D, Ovrevik J, Bakke O, Schwarze PE,
Refsnes M (2010). “Cadmium-induced inflammatory
responses in cells relevant for lung toxicity: Expression
and release of cytokines in fibroblasts, epithelial cells
and macrophages”, Toxicol Lett, 193 (3), 252-60.
36
Melhus G, Brorson SH, Baekkevold ES, Andersson
G, Jemtland R, Olstad OK, Reinholt FP (2010). ”Gene
expression and distribution of key bone turnover
markers in the callus of estrogen-deficient, vitamin
D-depleted rats”, Calcif Tissue Int, 87 (1), 77-89.
Progida C, Cogli L, Piro F, De Luca A, Bakke O, Bucci C
(2010). “Rab7b controls trafficking from endosomes to
the TGN”, J Cell Sci., 123 (9):1480-91.
Roux A, Koster G, Manneville J.-B., Sorre B, Nassoy P,
and Bassereau P (2010). “Membrane control of dynamin
polymerization”, Proc Natl Acad Sci U S A 107, 4141-4146.
Ruffini PA, Grødeland G, Fredriksen AB, Bogen B (2010).
”Human chemokine MIP1α increases efficiency of
targeted DNA fusion vaccines”,Vaccine, 29 (2), 191-9.
Stamnaes J, Dorum S, Fleckenstein B, Aeschlimann D,
Sollid LM (2010). ”Gluten T cell epitope targeting by TG3
and TG6; implications for dermatitis herpetiformis and
gluten ataxia”, Amino Acids, 39 (5), 1183-91.
Stamnaes J, Pinkas DM, Fleckenstein B, Khosla C, Sollid
LM (2010). ”Redox regulation of transglutaminase 2
activity”, J Biol Chem, 285 (33), 25402-9.
Tutturen AE, Holm A, Jørgensen M, Stadtmüller P, Rise
F, Fleckenstein B (2010). ”A technique for the specific
enrichment of citrulline-containing peptides”, Anal
Biochem, 403 (1-2), 43-51.
Tveito K, Brunborg C, Bratlie J, Askedal M, Sandvik L,
Lundin KE , Skar V (2010). ”Intestinal malabsorption of
D-xylose: comaprison of test modalities in patients with
celiac disease”, Scand J Gastroenterol, 45:1289-94.
Walseng E, Furuta K, Bosch B, Weih KA, Matsuki Y,
Bakke O, Ishido S, Roche PA. “Ubiquitination regulates
MHC class II-peptide complex retention and degradation
in dendritic cells”, Proc Natl Acad Sci U S A 107, 204670.
Wegner CS, Malerød L, Pedersen NM, Progida C,
Bakke O, Stenmark H, Brech A (2010). ”Ultrastructural
characterization of giant endosomes induced by GTPasedeficient Rab5”, Histochem Cell Biol., 133(1):41-55.
Other papers
Jahnsen FL (2010). “Redusert barrierefunksjon og
immunpatologi ved atopisk dermatitt”, Allergi i Prakis
1/2010.
Sandvik A (2010). ”Senter for immunregulering med
minisymposium om antigenpresentasjon”, NBS-nytt
6/2010.
Books and book chapters
Andersen JT and Sandlie I. Book chapter:
”Pharmacokinetics of Immunoglobulin G and Serum
Albumin: The Impact of the Neonatal Fc Receptor
on Drug Design”. Drug Delivery in Oncology - From
Research Concepts to Cancer Therapy. Edited by Feliz
Kratz, Peter Senter and Henning Steinhagen. Published
by WILEY-VCH (in press).
Bogen, B. Book chapter: ”Lymphoproliferativ
kreftsykdom og primære immundefekter”. Klinisk
biokjemi og fysiologi. Gyldendal Akademisk 2010.
Brandtzaeg P. Book chapter: “Immune functions of
nasopharyngeal lymphoid tissue”. Advances in OtoRhino-Laryngology (Proceedings of the 7th Internat.
Symp. on Tonsils and Mucosal Barriers of Upper
Airways, Asahikawa, Japan, July 7-9, 2010). Edited by
Hayashi T. Karger (in press).
Brandtzaeg P. Book chapter: “The intestinal immune
system”. Diet, Immunity and Inflammation. Edited by
Calder PC and Yaquob P. Woodhead (in press).
Brandtzaeg P. Book chapter: “The intestinal immune
system in health”. Crohn’s Disease and Ulcerative Colitis.
Edited by Baumgart D. Springer (in press).
Brandtzaeg P. Book chapter: ”Hvorfor øker forekomsten
av allergi og astma?”. Aktuell Nordisk Odontologi. Edited
by Holmstrup P. Munksgaard, København (in press).
Brandtzaeg P and Pabst R. Book chapter: “Structure and
histology of the immunologically functional mucosal
layers”. Mucosal Immunology. Edited by Smith P,
MacDonald T, Blumberg R. Garland Science, Taylor &
Francis Group (in press).
Spencer J and Brandtzaeg P. Book chapter: “Lymphocytes
– B cells”. Mucosal Immunology. Edited by Smith P,
MacDonald T, Blumberg R. Garland Science, Taylor &
Francis Group (in press).
Johansen F-E, Massol R, Baker K, Fiebiger E, Blumberg
RS, and Lencer WI. Book chapter: “Biology of Gut
Immunoglobulins”. Physiology of the Gastrointestinal
Tract, Fifth Edition. Editor in chief, Leonard R. Johnson.
Academic Press (in press).
Kenanova VE, Olafsen T, Andersen JT, Sandlie I and Wu
AM.
Book chapter: “Engineering of the Fc Region for
Improved PK (FcRn interaction)”. Antibody engineering
Volume 1, Second Edition, Springer Lab Protocols. Edited
by Roland Kontermann and Stefan Dübel, SpringerVerlag Berlin Heidelberg 2010.
Patents (accumulated)
Di Niro R, Sollid LM, Wilson PC: Identification
of antibodies in mucosal cells (US provisional,
US61/352/467).
Munthe LA, Carlsen H, Blomhoff R and Bogen B: Triple
transgenic mouse model of autoimmune disease and NFkB in vivo imaging (US provisional, US61/262/968).
Løset GÅ, Frigstad T, Sandlie I, Bogen B: Disulphide bondstabilized functional soluble MHC class II heterodimers
(US provisional, GB1002730.8)
Ruffini PA, Fredriksen A, Bogen B: Homodimeric protein
constructs (WO2010/61358513, EP10167291.3).
Løset GÅ: PVII phage display ( WO2009/024591).
Løset GÅ: Signal sequence –independent pIX phage
display ( WO2010/097411).
Reiersen H, Løset GÅ, Hagemann UB, Owen D: Method
for screening phage display libraries against each other
(WO2010/097589).
Andersen JT, Sandlie I (with Novozymes): Albumin
variants (EP10174162.7).
Andersen JT, Sandlie I (with Novozymes): Albumin
derivatives (EP10174164.3).
Johansen F-E, Sandvik A, Engstad RE: Methods of
treating or preventing inflammatory disease of the
intestinal tract (PCT/GB2008/003850).
37
Appendix 3
Presentations given outside CIR
Invited lectures
Bogen B: “Idiotype-driven T-B colaboration: a historical
perspective”. Course on NF-kB, inflammation and cancer,
University of Lausanne, April 23, Lausanne, Swizerland.
Brandtzaeg P: Er sekretorisk IgA nyttig?
Avslutningssymposium for Prof. Stig S. Frøland,
Rikshospitalet, June 15, Oslo, Norway.
Bogen B: “BCR handshakes: interacting B cells
undergo apoptosis”. Institute seminar, Department
of Biochemistry, University of Lausanne, April 23,
Lausanne, Swizerland.
Brandtzaeg P: “Immune functions of nasopharyngeal
lymphoid tissue”. The 7th International Symposium on
Tonsils and Mucosal Barriers of the Upper Airways, July
7, Asahikawa, Japan.
Bogen B: “Individualized Idiotypic DNA vaccines for
multiple myeloma patients”. The Nordic Myeloma Study
Group Translationonal Collaborative Research Meeting,
October 20, Copenhagen, Denmark.
Brandtzaeg P: “Mucosal immunization”. International
Workshop on Oral Immunization of Children in
Low Income Countries and the Role of the Intestinal
Microbiota in Regulating Immune Responsiveness,
August 17, Goa, India.
Bogen B: “DNA vaccine that encodes APC-targeted
vaccine protein protect mice against H1N1 influenza”.
Gene-Based Vaccines 2010, November 8, Cannes, France.
Brandtzaeg P: “LIIPATs involvement in Cross-Talk”.
Cross-Talk Network of Doctoral Schools (kick-off
meeting), January 12, Paris, France.
Brandtzaeg P: “Anti-inflammatory functions of IgA
reinforcing the mucosal barrier”. Cluster Lecture, Borstel
(Excellence Initiative “Inflammation at Interfaces”),
January 26, Kiel, Germany.
Brandtzaeg P: “Commensal bacteria and secretory
immunity are two mutual determinants of
immunological homeostasis”. MetaHIT Conference on
Human Metagenomics, March 3, Shenzhen, China.
Brandtzaeg P: “Induction, dissemination and function of
mucosal B cells”. Modern Mucosal Vaccines, Adjuvants
and Microbicides, April 28, Dublin, Ireland.
Brandtzaeg P: “B and T cells in the human mucosal
immune system”. Adjuvant 2010 - 5th International
Workshop on Vaccine Adjuvants and Parasitic Vaccines,
May 17, Trinidad, Cuba.
Brandtzaeg P: “The importance of secretory immunity
for immunological homeostasis”. Adjuvant 2010 - 5th
International Workshop on Vaccine Adjuvants and
Parasitic Vaccines, May 17, Trinidad, Cuba.
Brandtzaeg P: “Difference between mucosal immuneinductive sites in humans and animals”. Adjuvant 2010
- 5th International Workshop on Vaccine Adjuvants and
Parasitic Vaccines, May 17, Trinidad, Cuba.
38
Brandtzaeg P: “Immunomodulatory role of
intestinal epithelium: Role of T cells and dendritic
cells”. Symposium on Mediators and Cell Types in
Gastrointestinal Inflammation: Therapeutic Implication
for the Treatment of IBD and IBS, September 16,
Antwerp, Belgium.
Brandtzaeg P: “Basic principles of mucosal immunity”.
First Advanced Vaccinology Course in India, September
20, Vellore, India.
Brandtzaeg P: “Maternal antibodies and their role in the
neonate”. First Advanced Vaccinology Course in India,
September 20, Vellore, India.
Brandtzaeg P: “Correlates of protection: How to measure
antibody responses to oral vaccines”. First Advanced
Vaccinology Course in India, September 21, Vellore, India.
Brandtzaeg P: “Does bacterial overgrowth explain poor
“take” of oral vaccines in developing countries?”. First
Advanced Vaccinology Course in India, September 21,
Vellore, India.
Brandtzaeg P: “Mucosal vaccines and pitfalls in animal
models”. First Advanced Vaccinology Course in India,
September 21, Vellore, India.
Brandtzaeg P: “Chronic inflammatory disorders: Similar
treatment – similar immunopathology?”. Essentials
of Anti-TNF Treatment (A Nordic interactive crossdisciplinary scientific symposium on TNF-blockade in
immune-mediated diseases), September 24, Copenhagen,
Denmark.
Corthay A: “How does our immune system protect
us against cancer?”. Louis Pasteur Center for Medical
Research, August 20, Kyoto, Japan.
Lundin KE: “Three days oral gluten challenge – response
in gluten sensitive individuals with and without celiac
disease”. Second International Symposium on Glutenfree Cereal Products and Beverages, June 8, Tampere,
Finland.
Lundin KE: “Genetic susceptibility in celiac disease”.
Scandinavian Society for Gastroenterology meeting, June
10, Copenhagen, Denmark.
Olsen I: “Isolation of Mycobacterium avium subspecies
paratuberculosis antigen reactive T-lymphocytes from
intestinal biopsies from Crohn’s patients”. 8th BMRP
Investigator meeting, February 18, Los Angeles, CA, USA.
Sandlie I: “The half-lives of human IgG subclasses”.
Antibody Biology and Engineering Gordon Research
Conference, March 7, Ventura, CA, USA.
Sollid LM: “MHC peptide off-rate and peptide
deamidation as factors in the anti-gluten T cell responses
in celiac disease”. 2010 Warren Celiac Research
Symposium, April 9, La Jolla, CA, USA.
Sollid LM: “Autoimmunity: Lessons from coeliac
disease”. XXXII Nordic Congress in Medical
Biochemistry, June 1, Oslo, Norway.
Sollid LM: “Genetic control of celiac disease”. 9th
Meeting of Scandinavian/Baltic Society for Immunology,
June 2, Tallin, Estonia.
Sollid LM: “Is innate immunity activation necessary
for celiac disease?”. European Laboratory for the
investigation of food induced diseases 2001-2010.
September 15, Naples, Italy.
Sollid LM: “Immunology of celiac disease”. European
Mucosal Immunology Group Meeting, September 29,
Amsterdam, The Nederlands.
Sollid LM: “Dissecting celiac disease by analysis of
immune cells from the disease lesion”. Irish Society for
Immunology 25th Anniversary Symposium, October 15,
Dublin, Ireland.
Sollid LM: “The IgA anti-transglutaminase 2 response
in coeliac disease”. United European Gastroenterology
Week, October 23, Barcelona, Spain.
Sollid LM: “Celiac disease”. Symposium: Mechanisms
of autoimmune diseases 2010, November 12, Hamburg,
Germany.
Sollid LM: “Dissecting gluten sensitive enteropathy
by analysis of cells in the disease lesion”. CHIP
meeting - Intestinal inflammatory diseases, November
19, Lund, Sweden.
Sollid LM: “Pathogenesis of autoimmunity: Potential role
of modified autoantigens”. JDRF Meeting: Role of beta
cell antigen modifications in the pathogenesis of T1D and
their diagnostic and therapeutic potential, December
13, New York, USA.
Sollid LM: “Autoimmune dysregulation in celiac
disease”. Danish Society for Immunology, December 16,
Copenhagen, Denmark.
Sollid LM: “Gluten specific -cell responses in celiac
disease”. 4th Measurement of Antigen Specific Immune
Responses Meeting, June 9, Mykonos, Greece.
Sollid LM: “Transglutaminase 2 and celiac disease”.
Gordon Resarch Conference on Transglutaminases in
Human Disease Processes, July 18, Davidson, NC, USA.
39
Oral presentations
Berg-Larsen A: “Rab-protein expression during
DC-maturation”. Gordon Research Conference for
Immunochemistry & Immunobiology, May 16, Les
Diablerets, Switzerland.
Haabeth O-AW: “Tumor-specific inflammation protects
against cancer”. 14th International Congress of
Immunology, August 22, Kobe, Japan.
Islam R: “Effect of IgA on Microbial composition and
distribution in colitis model”. Network and training
Cross-talk meeting, August 30, Debrecen , Hungary.
Iversen R: “Mechanisms underlying the production of
anti-transglutaminase 2 autoantibodies in response
to gluten intake in coeliac disease”. 14th International
Congress of Immunology, August 22, Kobe, Japan.
Jahnsen FL: “Mutations in the fatty acid transporter
protein (FATP) 4 gene induce elevated IgE, eosinophilia
and atopic disorders including atopic dermatitis-like
skin lesions”. 28th Symposium Collegium Internationale
Allergologicum, April 25, Ischia, Italy.
Ráki M: “Serology in celiac disease”. CDMedics, April 29,
Budapest, Hungary.
Sandvik A: “Ectopic expression of cryptdins in colon of
mice lacking secretory Immunoglobulins”. European
Poster presentations
Baekkevold ES: “Human airway mucosal DCs respond
to TSLP and induce Th2 responses”. 11th International
Symposium on Dendritic Cells in Fundamental
and Clinical Immunology, September 26, Lugano,
Switzerland.
Beitnes A-CR: “CD103+ dendritic cells are present, but
do not increase in contrast to dendritic cells expressing
macrophage markers in the celiac lesion”. European
Danilova E: “The steady-state chemokine expression
profile in human nasal mucosa”. World Immune
Regulation Meeting-IV, March 29, Davos, Switzerland.
40
Di Niro R: “Abundance in the celiac lesion of cells
secreting transglutaminase 2 specific IgA autoantibodies
with features of a primary response”. The 4th
International Conference on B cells and Autoimmunity,
August 19, Nara, Japan.
Di Niro R: “In celiac disease a unique population of
IgA secreting cells with low degree of hypermutation
accounts for the extraordinarily high antitransglutaminase 2 response in the gut”. 14th
International Congress of Immunology, August 22, Kobe,
Japan.
Fossum E: “Targeted vaccibodies against Mycobacterium
tuberculosis”. TB Vaccines: A Second Global Forum,
September 21, Tallin, Estonia.
Grcic V: “Ectopic expression of cryptdins in colon of
mice lacking secretory Immunoglobulins”. MetaHIT
conference, March 1, Shenzhen, China.
against cancer”. 14th International Congress of
Immunology, August 22, Kobe, Japan.
Grodeland G: “Targeted DNA vaccine protect mice
against H1N1 influenza”. Meeting the Challenges of the
Millenium Developmental Goeals and Byond - Health
Research and policy, December 2, Washington, DC, USA.
Islam R: “Regulation of polymeric Immunoglobulin
receptor (pIgR) expression in epithelial cells by IL-17 and
other cytokines”. 1st MetaHIT Conference on Human
Metagenomics, March 1, Shenzhen, China.
anti-transglutaminase 2 autoantibodies in response to
gluten intake in coeliac disease”. The 4th International
Conference on B cells and Autoimmunity, August 19,
Nara, Japan.
anti-transglutaminase 2 autoantibodies in response
to gluten intake in coeliac disease”. 14th International
Congress of Immunology, August 22, Kobe, Japan.
Landsverk OJB: “Rab effectors in the Invariant chain
induced endocytic pathway”. Keystone Symposia Molecular Basis for Biological Membrane Organization
and Dynamics, January 10, Snowbird, UT, USA.
Brandtzaeg P: “Breast milk and immunity”. Lecture:
Immunity and nutrition and adverse reactions to food,
March 15, Univeristy of Oslo, Department of Nutrition,
Oslo, Norway.
Lorvik KB: “Proteomics of tumor-specific CD4+ T cells”.
14th International Congress of Immunology, August 22,
Kobe, Japan.
Brandtzaeg P: ”Tarmbarrierens betydning for
immunologisk homeostase”. Forelesning, Kveldskurs for
leger, BMLab, June 3, Oslo, Norway.
Reikvam DH: “Absence of the polymeric immunoglobulin
receptor protects B cell-deficient mice from colitis”.
European Mucosal Immunology Group Meeting,
September 29, Amsterdam, The Nederlands.
Brandtzaeg P: ”Hvorfor øker allergier –
fremtidsperspektiv?” Forelesning, emnekurs
ved primærmedisinsk uke: Matallergi og annen
matoverfølsomhet, Den norske legeforening og Astmaog Allergiforbundet, October 26, Oslo.
Skrindo I: “Rapid IL-5 production by allergen-specific
T cells in an ex vivo model of allergic rhinitis”. 29th
Congress of the European Academy of Allergy and
Clinical Immunology, June 5, London, UK.
Aas-Hansen K: ”Mouse model for SLE-like disease”.
The 4th International Conference on B cells and
Autoimmunity, August 19, Nara, Japan.
Presentations to a targeted audience
and the public
Amundsen SS: ”Cøliaki – med fokus på arvelighet”.
Messen “Mat for livet”, November 6, Oslo, Norway.
Bakke O: ”Cellular imaging in the immune system”.
Molecular Biology Research PhD School 2010,
Biotechnology Centre Oslo, November 10, Oslo, Norway.
Bogen B: ”Novel vaccine molecules for influenza”. Møte i
Regionalt Forskningsutvalg, March 10, Oslo, Norway.
Bogen B: ”Kreftvaksiner – hvor står vi hen?”. Universitet
i Oslo, Institutt for medisinske basalfags foredragsserie
”Menneskekroppen og sykdom – ny innsikt fra
biomedisinsk grunnforskning”, April 7, Oslo, Norway.
Brandtzaeg P: “Food and allergy”. Lecture: Immunity
and nutrition and adverse reactions to food, March
15, Univeristy of Oslo, Department of Nutrition, Oslo,
Norway.
Brandtzaeg P: “Organisation of biobanks at our hospital:
Compliance with the EU rules?” Regional forskningsetisk
komité (REK Sør-Øst), Studiebesøk hos Den norske
EU-delegasjon og European Commission, November 11,
Brüssel, Belgium.
Brandtzaeg P: ”Hvorfor er matallergi et økende
problem?”. P2-akademiet (Red.: Høghaug L). Transit/
Vidarforlaget, Oslo, Norway.
Corthay A: “Tumor-specific inflammation protects
against cancer”. Internal seminar series, University of
Oslo, Centre for Molecular Biology and Neuroscience,
Oslo, Norway.
Fredriksen AB: ”Moderne vaksiner finner frem til
kroppens vaktposter på egenhånd”. Immunologiens dag,
April 29, Oslo, Norway.
Gregers TF: ”An endosomal tour guided by invariant
chain”. Department seminar, University of Oslo, IMBV,
March 18, Oslo, Norway.
Gregers TF: ”Vaksinasjon - et immunforsvar i
beredskap”. Immunologiens dag, April 29, Oslo, Norway.
Gregers TF: ”An endosomal tour guided by invariant
chain”. CIR minisymposium – Antigen presentation,
September 17, Oslo, Norway.
41
Gregers TF: ”Hva er en forsker?”. Lysejordet Skole,
October 13, Oslo, Norway.
Grodeland G: “Targeted DNA vaccine protect mice
against H1N1 influenza”. CIR minisymposium – Antigen
presentation, September 17, Oslo, Norway.
against cancer”. Bio-Plex User Meeting, May 18,
Copenhagen, Denmark.
Jahnsen FL: ”Generell anatomi i mage og tarm”.
Histoteknikerforeningen, February 2010, Holmenkollen
park, Oslo, Norway.
Jahnsen FL: “Immune system in allergy”. Postgraduate
lecture for pediatricians, March 22, 2010, OUS
Rikshospitalet, Oslo, Norway.
Jahnsen FL: “Redusert hudbarriere som årsak til atopisk
sykdom”. Voksentoppseminaret, December 2010, OUS
Rikshospitalet, Oslo, Norway.
Koster G: Department seminar, University of Oslo, IMBV,
Oslo, Norway.
Koster G: Advanced course in live cell imaging, June 8,
Oslo, Norway.
Landsverk OJB: ”Illustrator for scientific presentation”,
OUS-Radiumhospitalet, June 14, Oslo, Norway.
Lundin KE: ”Cøliaki – klinisk oppdatering og informasjon
om ny testmetode med korttids provokasjon”. Foredrag
for Buskerud NCF, February 18, Norway.
Lundin KE: ”Moderne IBD behandling”. Foredrag på
obligatorisk kurs for indremedisin innen gastromedisin
og – kirurgi, Rikshospitalet, June 14, Oslo, Norway.
42
Lundin KE: ”Cøliaki”. Foredrag på 2 dagers kurs
for allmenmedisinere om matvareintoleranse,
Rikshospitalet, February 15, Oslo, Norway.
Lundin KE: ”Cøliaki og gluten fri kost”. Foredrag på
B-gren kurs om tarmsykdommer, kurs nr 25077.
Sykehuset Asker og Bærum, November 3, Gjettum,
Norway.
Lundin KE: ”Problemer etter tarmoperasjoner”. Foredrag
på B-gren kurs om tarmsykdommer, kurs nr 25077.
Sykehuset Asker og Bærum, November 3, Gjettum,
Norway.
Lundin KE: ”Cøliaki”. Foredrag etterutdanningskurs
kliniske ernæringsfysiologer. Bjørvika konferansesenter,
November 4, Oslo, Norway.
Skjeldal FM: “Early endosomal fusion stimulates tubule
formation and molecular motor driven vesicular fission”.
Advanced course in live cell imaging, June 8, Oslo,
Norway.
Skrindo I: ”Mekanismer ved allergi i øvre luftveier”.
Norsk forening for Allergologi og Immunpatologi,
October 28, Oslo, Norway.
Sollid LM: “Cøliakiforskning”. Årsmøte Norsk
Cøliakiforening, February, Oslo, Norway.
Høydahl LS: “Regulating the immune response; the effect
of metal ions on the IgG:FcgR interaction”. Joint CIR and
NSI guest lectures and immunology happy hour, May 6,
Oslo, Norway. Øynebråten I: “Vaccine development for HIV”. University
of Oslo, Institute for Basic Medical Sciences, Oslo,
Norway.
Appendix 4
Bakke O: ”Mikroskopisk revolusjon”. Uniforum, June 17.
Bogen B/Vaccibody AS: ”Få forskere med aksjer”.
Finansavisen, January 15, p. 34-35.
Dørum S: ”Nøkkelenzym ved cøliaki”. Dagens Medisin,
October 21.
Lundin KE. ”Hva lurer du på om glutenfri kost”, God
Morgen Norge, TV2, September 21.
Media coverage
Løset GÅ: ”Gir kreft- og MS-pasientar nytt håp”,
Uniforum, April 15.
Sollid LM: “Jaktar på cøliaki-mysteriet”. Uniforum,
December 14.
Vaccibody AS: ”One to watch”. Oslo Teknopol, Bio
Update, May.
CIR omtale: “Livet etter oljedøden”. Dagsavisen, April 24.
Mucus producing Goblet cells (blue “baloons”, AB-PAS stain) in the colon of a healthy mouse. Photo: Anders Sandvik.
43
Appendix 5
Collaboration
National
Silke Appel, Broegelmann Res. Lab., University of Bergen
Harm-Gerd Blaas, Dept. of Gynecology and Obstretics,
St. Olavs Hospital, Trondheim
Heidi Kiil Blomhoff, Institute of Basic Medical Sciences,
University of Oslo
Rune Blomhoff, Institute of Basic Medical Sciences,
University of Oslo
Bjørn Dalhus, Centre for Molecular Biology and
Neuroscience, Univ. of Oslo and Oslo Univ. Hospital
Fridtjof Lund-Johansen, Dept. of Immunology, Oslo
University Hospital
Margaretha Johnsson, Dept. of Dermatology, St. Olavs
Hospital, Trondheim
Trond Leren, Dept. of Medical Genetics, Oslo University
Hospital
Inger Helene Madshus, Dept. of Pathology, University of
Oslo
Terje E. Michaelsen, Norwegian Institute for Public
Health, Oslo
Rolf Engstad, Biotec Pharmacon ASA, Tromsø
Terje Espevik, Norwegian University of Science and
Technology, Trondheim
Peter Gaustad, Dept. of Medical Microbiolology,
University of Oslo and Oslo University Hospital
Tobias Gedde-Dahl d.y., Dept. of Haematology, Oslo
University Hospital
Johanna Olweus, Institute for Cancer Research, Oslo
University Hospital
Norbert Roos, Dept. of Molecular Biosciences, University
of Oslo
Jan Cezary Sitek, Dept. of Dermatology, Oslo University
Hospital
Einar Gran, Lovisenberg Hospital, Oslo
Anne Spurkland, Institute of Basic Medical Sciences,
University of Oslo
Harleen Grewald, Gades Institute, Univeristy of Bergen
and Haukeland University Hospital
Harald Stenmark, Centre for Cancer Biomedicine, Univ.
of Oslo and Oslo Univ. Hospital
Krzysztof Grzyb, Dept. of Pathology, Oslo University
Hospital
Elisabeth Søyland, Norwegian Medical Association
Guttorm Haraldsen, Dept. of Pathology, University of
Oslo and Oslo University Hospital
Geir Tjønnfjord, Dept. of Haematology, Oslo University
Hospital
Harald Holte, Dept. of Oncology, Oslo University
Hospital
International
Jørgen Jahnsen, Department of Medicine, Aker Hospital,
Oslo
Dan Barouch, Harvard University, US
Kjetill S. Jacobsen, Centre for Ecological and Evolutionary
Synthesis, University of Oslo
Daniel Aeschlimann, University of Wales, Cardiff, UK
Francisco Barro, Instituto de Agricultura Sostenible,
Cordoba, ES
Richard S. Blumberg, Harvard Medical School, US
Benedicte A. Lie, Dept. of Medical Genetics, University of
Oslo
44
Harald von Boehmer, Harvard University, US
Kurt Bommert, University of Würzburg, DE
Åsa Torinsson Naluai, Gothenburg University, SW
Cecilia Bucci, University of Salento, Lecce, IT
Jacques Neefjes, Netherlands Cancer Institute,
Amsterdam, NL
Søren Buus, University of Copenhagen, DK
Morten S. Nielsen, University of Aarhus, DK
Blaise Corthésy, University of Lausanne, CH
Claus Munck Petersen, University of Aarhus, DK
Morten Dziegiel, Rigshospitalet - Copenhagen University
Hospital, DK
Klaus Rajewsky, Harvard University, US
Caroline Ekblad, Affibody AB, Stockholm, SW
Paul Roche, NIH, US
Peter M. Elias, University of California San Francisco, US
Derry C. Roopenian, The Jackson Laboratory, US
Laszlo Fesus, University of Debrecen, HU
Janneke Samson, Erasmus University Medical Center, NL
Johan Garssen, University of Utrecht and Danone
Research Centre for Specialised Nutrition, NL
Daniele Sblattero, University of Piemonte, IT
Mark Shlomchik, Yale University, US
Georg Georgiou, University of Texas, US
Hauke Smidt, Wageningen University, NL
Carmen Gianfrani, Institute of Food Sciences, Avellino, IT
Patrick Holt, Telethon Institute of Child Health Research,
Perth, AU
Gestur Vidarsson, Sanquin Research, University of
Amsterdam, NL
Reinhard Voll, University of Erlangen-Nürnberg, DE
Bertrand Huard, University of Geneva, CH
Patrick Wilson , University of Chicago, US
Bana Jabri, University of Chicago, US
Chaitan Khosla, Stanford University, US
Cisca Wijmenga, University Medical Center Groningen,
NL
Chu-Young Kim, National University of Singapore, SI
Anna Wu, University of California Los Angeles, US
Frits Koning, Leiden University Medical Center, NL
Hideo Yagita, Jutendo University, JP
Wayne Lencer, Harvard Medical School, US
Dov Zipori, Weizmann Institute, IS
Markku Mäki, University of Tampere, FI
Kristiina Malmstrøm, Helsinki University, FI
Jeffery Miner, Washington University School of
Medicine, US
45
Appendix 6
Funding and expenditures
Funding (1000 NOK)*
2010
Transferred from 2009 5 526
Research Council of Norway (RCN) – CoE
8 624
Oslo University Hospital (OUS) 3
24 934
Other public funding 4
4 654
International funding 6
Total funding** Expenditures (1000 NOK)*
Personnel costs 7
5 515
16 214
University of Oslo (UiO) 2
Private funding 5
1
1 590
67 056
2010
53 798
Equipment 662
Other operating expenses 14 330
Total expenditures 68 790
1. Including equal opportunities grant of 530 KNOK. Budgeted CoE funding 11030 KNOK. Transfer of second instalment from RCN
to CIR in 2010 delayed.
2.Including value of personnel funded by UiO and indirect costs of infrastructure.
3.Including value of personnel funded by OUS and indirect costs of infrastructure.
4.Including other grants from the RCN and grants from South-Eastern Norway Regional Health Authority.
5.Including grants from the Norwegian Cancer Society, the Norwegian Foundation for Health and Rehabilitation, Biotec
Pharmacon ASA, Vaccibody AS and others.
6.Including EU grants, grants from the Juvenile Diabetes Research Foundation, the Broad Foundation, the Swiss National Science
Foundation and others.
7.Including indirect costs.
* Accounting figures from the University of Oslo and Oslo University Hospital
**Due to delayed transfer of the second instalment of RCN-CoE funding in 2010, the balance for 2010 is negative. Transfer of funds
according to the funding plan and budget would have resulted in a small surplus.
46
Cell of love. CIR scientists are passionate about cell biology. Heart shaped nucleus (green) and rab5 protein (red) in a fibroblast.
Photo: Frode M. Skjeldal.
47
Ce
ion
IR
n tr
e fo
lat
r Immune Regu
Centre for
Immune Regulation
Visiting address | Oslo University Hospital-Rikshospitalet
Sognsvannsveien 20, Building A2/A3, N-0027 Oslo
Mailing address | OUS HF, Rikshospitalet P.O. box 4956 Nydalen, N-0424 OSLO, Norway
design | essenz.no
Phone: (+47) 23 07 35 00
Fax: (+47) 23 07 35 10
Email: post@cir.uio.no
Web:www.cir.uio.no

CIR Annual report 2010

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Oslo, Norway Aug 8–13th 1857 The Ventriloquist Summerschool

Crazy Copyright Cases

weekend suggestions - Oslo Chamber of Commerce

Scarcity and Creativity

weekend suggestions - INN - Oslo Chamber of Commerce

Travel to Norway