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Saez-Rodriguez et al. 2007 PLoS Comput.Biol.

The immune system has to discriminate pathogens (e.g. bacteria or viruses and cancerous cells) from healthy cells within our body. Foreign cells should be attacked and eliminated, whereas self-tissues should not be harmed. The main cell type involved in this decision is the T-cell.

T-cell activation is a complex process relying on multiple layers of tightly controlled intracellular signaling molecules, which form an intricate and dynamic network. Defects in this network can cause autoimmune responses that destroy normal body cells: Horror autotoxicus. This term was coined by the bacteriologist and immunologist Paul Ehrlich (1854-1915) to describe the body's immunological self-destruction in severe disorders such as multiple sclerosis. In order to understand and predict the behaviour of this network it is therefore crucial to study it as a complete system and not only its isolated parts.

Through a multidisciplinary effort SYBILLA aims to understand at systems level, how T-cells discriminate foreign- from self-peptides by activating quantitatively distinct signaling pathways. Data obtained in mouse models are extended to human T cells and to a mouse model of multiple sclerosis.
SYBILLA develops new analytical and mathematical tools to generate and integrate high-density quantitative data describing T-cell activation. Proteomics, transcriptomics, imaging and biochemical techniques will be applied to obtain holistic maps of the T-cell signaling network and to achieve a quantitative and dynamic understanding of signaling networks and their regulation in response to different signal inputs.
Building upon already existing schemes of the network connectivity, constant iteration between experiment and mathematical modelling will be used to develop robust and predictive models that describe the functioning of the T-cell signaling network. SYBILLA will allow the identification of new drug targets and the discovery of new biomarkers to refine prognosis of autoimmune diseases.

Publications of the SYBILLA consortium will be posted here in the future.

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