Objective
T cells have a central role in the bodys immune response to pathogens and other disorders such as in cancer and autoimmune disorders. T cells are constantly moving and this migration involves the interactions of different adhesion molecules such as the integrins. One important member of this family is the integrin LFA-1. When this integrin binds to its ligand ICAM-1, it has an adhesive function but it also has a key role in signalling. The Hogg lab has shown that the binding of LFA-1 to ICAM-1 signals reorganisation of the cytoskeleton and motility in the T cell. In fibroblasts and endothelial cells, the regulation of integrin-containing adhesions is dependent on a Ca2+-requiring cysteine protease called calpain. The Hogg lab has demonstrated that calpain is involved in formation of the LFA-1-mediated adhesions made by T cells and that it has a specific role in the de-adhesion of the migrating T cell. The applicant has evidence that the activation of calpain is dependent on the G protein heterodimer G12/13 an d also on phospholipase C which can give rise to the Ca2+ flux necessary for calpain activity. The aim of the proposed project is to identify the individual signalling pathway members leading from G12/13 to active calpain and, secondly, to understand how they affect T cell migration. Briefly we will identify the downstream elements from G12/13 and we will first investigate the role of GTPase Rho and its major effector Rho kinase and also the role of PLCepsilon. Importantly, we will link these findings to a lteration of T cell migration and look in more detail at specific alteration of LFA-1 adhesions. T cells spend most of their lives either circulating in and out of lymph nodes as naïve cells or, following exposure to antigen, migrating into other tissues. Therefore it is of great importance to understand the mechanisms behind this migration and ultimately to offer the possibility of intervention in patients with abnormal immune responsiveness.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine oncology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
FP6-2005-MOBILITY-5
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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.
Coordinator
LONDON
United Kingdom
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.