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Content archived on 2024-05-27

Protease signaling in development and disease

Objective

Protease- activated receptors (PARs) comprise a family of four G-protein coupled receptors that mediate cellular responses to proteases. PARs were identified in a search for the platelet receptor for the coagulation protease thrombin. Mouse deficiency models later established critical roles for PARs in hemostasis and thrombosis and in vascular development, yet unexplained functions ascribed to proteases hinted at a broader functional repertoire. To uncover new roles for PARs, we addressed redundancy between PARs and found that combined loss of all PARs in mice resulted in embryonic lethality not accounted for by bleeding or lack of endothelial signaling, suggesting unappreciated roles for PARs in development. Addressing redundancy with other signaling systems, we found that loss of plasma sphingosine-1-phosphate (S1P), a lipid agonist for a related family of G-protein coupled receptors, had profound effects on endothelial barrier homeostasis including sensitization to barrier modulation by PARs. This proposal aims to explore a novel role for PARs in development of the cardiovascular system and to study the role of PARs and S1P receptors and their interaction in endothelial barrier homeostasis. Better understanding of PARs, their agonist proteases and redundant signaling systems in embryonic development and adult disease may refine the use of existing and emerging drugs targeting this system and, potentially, expand their application beyond current indications.

Fields of science (EuroSciVoc)

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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.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2009-RG
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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.

MC-IRG - International Re-integration Grants (IRG)

Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
EU contribution
€ 100 000,00
Total cost

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.

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