SYSTEMS BIOLOGY OF T-CELL ACTIVATION Background
Achievements
T cells of the immune system can distinguish foreign
During the first 2.5 years SYBILLA has set up new stan-
antigens, that should be attacked, from autoantigens,
dardized transcriptomic, proteomic and biochemical
that should be ignored. For their activation a tightly con-
technologies to study the T-cell network with unprece-
trolled intracellular signalling network has to be trigge-
dented precision.
red. Defects in this network can cause severe disorders
Using these technologies in combination with mathe-
such as autoimmune diseases, where autoantigens are
matical modelling allowed to discover new mechanisms
attacked. Although 5% of the population suffer from
of how the TCR becomes activated upon antigen-bin-
these diseases, efficient therapeutic treatments are not
ding and how T cells distinguish self from auto antigens.
available; partly due to the lack of systems-level insight,
Novel proteins and mRNAs were identified that play a
which would provide concepts of how to modulate T-cell
role in T cell activation and differentiation. In addition,
activation. Although many of the elements and connec-
several large scale proteomics and transcriptomics stu-
tivities of this complex network have been identified, a
dies are currently performed, that will allow to extend
comprehensive, dynamic model is missing.
Boolean and ODE-based models. Such an integrated understanding of the T-cell signal-
Thus, through a multidisciplinary effort SYBILLA aims to
ling network will allow to develop reliable biological
understand at systems level, how T-cells discriminate for-
and simulation models for the identification of biologi-
eign from autoantigens by activating quantitatively dis-
cal biomarkers, intracellular drug targets and elaborated
tinct signalling pathways.
systems to predict the impact of any kind of drugs on T-cell activation.
International Conferences organized by SYBILLA “T-cell signalling and technologies“, Prague, March 2010 “Molecular and systems immunology“, Turku, August 2010 “Signal transduction“, Weimar, November 2011 (in cooperation with the Signal Transduction Society) “Immunodeficiency and beyond“, Freiburg, March 2012 (in cooperation with the Centre for Chronic Immunodeficiency CCI and the CRC 620)
Partners
Academic partners Schamel, Wolfgang Faculty of Biology and CCI, University of Freiburg (D) Reth, Michael Max Planck Institute for Immunobiology, Freiburg (D) Acuto, Oreste Sir Williams Dunn School of Pathology, Oxford (UK) Fugger, Lars Weatherall Institute of Molecular Medicine,Oxford (UK) Alarcon, Balbino Centro Biologia Molecular, CSIC, Madrid (E) Baier, Gottfried Dept. Medical Genetics, Medical University, Innsbruck (A) Gstaiger, Matthis & Aebersold, Ruedi Institute for Molecular Systemsbiology, ETH-Zürich (CH) Höfer, Thomas DKFZ, BioQuant, Heidelberg (D) Lahesmaa, Riitta Turku Centre for Biotechnology, University of Turku (FIN) Malissen, Marie & Malissen Bernard Centre d’Immunologie INSERM-CNRS, Marseille-Luminy (F) Palmer, Ed Department of Biomedicine, University Hospital Basel (CH) Schraven, Burkhart & Lindquist, Jonathan Institute of Molec & Clinical Immunology, University of Magdeburg (D) Viola, Antonella Fondazione Humanitas per la Ricerca, Padova (I) Lähdesmäki, Harri Aalto University School of Science & Technology, Espoo (FIN) Hanninen, Arno University of Turku, Turku (FIN) Villoslada, Pablo Institute of Biomedical Research, Barcelona (E) Rao, Anjana Harvard Med School & Immune Disease Institute, Boston (USA) Rao, Kanury Internat. Centre for Genetic Engineer & Biotech, Delhi (IND) Mathis, Diane & Benoist, Christophe Joslin Diabetes Center, Harvard Med School, Boston (USA)
Industrial partners Suchanek, Miloslav EXBIO Praha, Antibody-producing Company, Vestec (CZ) Rival, Sandrine Novamen, Research Promotion and Managing Company, Lyon (F)
SYSTEMS BIOLOGY OF T-CELL ACTIVATION Scientific Publications
About Sybilla
35 scientific and 6 articles for a general audience were published until July 2011
The SYBILLA consortium is funded by the EU in FP7 with 11.1 mio Euro for 5 years (2008-2013) and lead by Wolfgang Schamel, Freiburg, Germany, as the scientific coordinator.
These include: Wepf et al., 2009, Nature Methods, partners Aebersold & Gstaiger Harkiolaki et al., 2009, Immunity, partner Fugger Mingueneau et al., 2009, Immunity, partners Malissen & Malissen Gruber et al., 2009, Science Signalling, partner Baier Palmer & Naeher, 2009, Nat Rev Immunol, partner Palmer Nika et al., 2010, Immunity, partners Viola, Fugger, Höfer & Acuto Moulder et al., 2010, Mol Cell Proteomics, partner Lahesmaa Swamy et al., 2010, Cell Comm Signalling, partners Schraven & Schamel
Contact Scientific Coordinator Prof. Wolfgang Schamel
Dept. of Molecular Immunology Faculty of Biology Centre for Chronic Immunodeficiency, CCI, University Freiburg Centre for Biological Signalling Studies, BIOSS, Max Planck Institute for Immunobiology and Epigenetics Stübeweg 51 79108 Freiburg Germany Tel : +49-(0)761-5108-313 Fax :+49-(0)761-5108-423
schamel@immunbio.mpg.de www.immunbio.mpg.de
Dopfer et al., 2010, Imm Lett, partners Exbio, Reth & Schamel
Management Partner
Elo et al., 2010, Immunity, partners Lähdesmäki & Lahesmaa
Dr. Sandrine Rival
Deswal et al., 2011, PLoS ONE, partners Höfer & Schamel Brockmeyer et al., 2011, J Biol Chem, partner Acuto Kumar et al., 2011, Immunity, partners Schamel & Alarcon Beyer et al., 2011, PLoS Comput Biol, partners Schraven & Lindquist
Open positions in an excellent environment are available at : www.sybilla-t-cell.de
Consultant Novaman 69 rue de la Republique 69002 Lyon France Tel : +33-(0) 478-924000 Fax :+33-(0) 478-924001 tcell@novamen.fr www.novamen.fr
SYBILLA large collaborative project on systems biology of T-cell activation
www.sybilla-t-cell.de