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)