Objective
A critical step of an immunological response is the activation of T lymphocytes through intracellular signaling pathways downstream of T cell receptors (TCR). THEMIS1 is a new actor of T cell signaling that belongs to a newly identified family of proteins. THEMIS proteins each contain a previously uncharacterized globular domain (called 'CABIT') whose structure and function are currently unknown. We generated THEMIS1 knockout mice and show that this protein is essential for developing T cells in the thymus. THEMIS1 is also express in CD4+ and CD8+ peripheral T cells. Since very few T cells egress to peripheral organs in THEMIS1 knockout mice, little is known about this protein during immune responses. THEMIS1 has recently been pointed out as a susceptibility factor in Celiac disease and Multiple sclerosis, and recent study in rats also revealed that THEMIS1 deficiency leads to the development of spontaneous inflammatory bowel disease. Whether this results directly from THEMIS1 deficiency in T cells or is a secondary effect due to the decrease numbers of T cells in lymphoid organs (lymphopenia) needs to be resolved. The objective of the present proposal is: 1) to perform a structural and functional analysis of THEMIS1 CABIT domains and to establish THEMIS1 interactome in T cells, 2) to determine the physiological and cellular role of Themis in peripheral T cells, 3) to study the contribution of Themis on the development of autoimmune and inflammatory diseases using experimental murine models. I discovered THEMIS proteins during my post-doctoral research at the National Institutes of Health (Bethesda, USA) and I have recently established a lab in France (sponsored by the French government) to pursue our researches on this new family of molecules. Additional supports are now essential to fully develop our projects that we believe could lead to major findings in structural biology, immunology and immunopathology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences cell biology cell signaling
- medical and health sciences health sciences inflammatory diseases
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences basic medicine immunology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2012-CIG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
75654 PARIS
France
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.