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Systems Biology of T-cell Activation in Health and Disease

Systems Biology of T-cell Activation in Health and Disease

Objective

T-cell activation, whether induced by pathogens or auto-antigens, is a complex process relying on multiple layers of tightly controlled intracellular signalling modules that form an intricate network. Defects in this network can cause severe and chronic disorders such as autoimmune diseases. Although 5% of the population suffer from these diseases, only a few therapeutic treatments are available. To a large extent this is attributed to the lack of systems-level insights, which would provide concepts of how to modulate T-cell activation. The SYBILLA project groups 14 partners from 9 different EU countries, including 3 SMEs. Through a multidisciplinary effort it aims to understand at the systems’ level, how T-cells discriminate foreign from auto-antigens. Towards this goal, a transgenic mouse system will be used as a tractable physiological model. Data will be validated in human T-cells and a humanised mouse model for multiple sclerosis. SYBILLA will develop technological and mathematical tools to generate and integrate high-density quantitative data describing T-cell activation. Proteomics, transcriptomics, metabolomics, imaging and multiplexed biochemical techniques will be applied to obtain holistic maps of T-cell signalling networks and to achieve a quantitative understanding of the network and its regulation in response to different inputs. Building upon our existing network model, constant iterations will be used to develop more robust dynamic models to describe the network’s response to perturbations. This will culminate in the generation of a Virtual T-Cell, allowing computer simulation to refine the predictability of physiological and pathophysiological reactions. SYBILLA’s impact on EU biopharmaceutical competitiveness will be enormous through identification of new pharmacologic targets, optimised prediction of immunomodulatory drug efficacy, discovery of new concerted biomarkers and improvement of personalised medication for treating autoimmune diseases.

Coordinator

ALBERT-LUDWIGS-UNIVERSITAET FREIBURG

Address

Fahnenbergplatz
79098 Freiburg

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 418 100,33

Administrative Contact

Wolfgang Schamel (Prof.)

Participants (21)

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NOVAMEN SAS

France

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 1 156 331

AGENCIA ESTATAL CONSEJO SUPERIOR DEINVESTIGACIONES CIENTIFICAS

Spain

EU Contribution

€ 581 154

MEDIZINISCHE UNIVERSITAT INNSBRUCK

Austria

EU Contribution

€ 583 375

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH

Switzerland

EU Contribution

€ 1 164 600

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG

Germany

EU Contribution

€ 582 136

TURUN YLIOPISTO

Finland

EU Contribution

€ 1 280 606

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 711 479

UNIVERSITATSSPITAL BASEL

Switzerland

EU Contribution

€ 514 000

OTTO-VON-GUERICKE-UNIVERSITAET MAGDEBURG

Germany

EU Contribution

€ 544 040

FONDAZIONE HUMANITAS PER LA RICERCA

Italy

EU Contribution

€ 546 000

MEDICEL OY

Finland

EU Contribution

€ 373 355,86

EXBIO PRAHA AS

Czechia

EU Contribution

€ 665 500

ACIES SAS

France

EU Contribution

€ 53 969,89

Immune Disease Institute

United States

INTERNATIONAL CENTRE FOR GENETIC ENGINEERING AND BIOTECHNOLOGY

Italy

Joslin Diabetes Center

United States

ACIES Consulting Group SAS

France

EU Contribution

€ 306 797,11

TTY-SAATIO

Finland

EU Contribution

€ 326 644,14

CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER

Spain

MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV

Germany

EU Contribution

€ 1 291 911,67

Project information

Grant agreement ID: 201106

Status

Closed project

  • Start date

    1 April 2008

  • End date

    30 September 2013

Funded under:

FP7-HEALTH

  • Overall budget:

    € 14 636 311,41

  • EU contribution

    € 11 100 000

Coordinated by:

ALBERT-LUDWIGS-UNIVERSITAET FREIBURG

Germany