Objective
Many biologically active molecules signal via membrane-bound receptors coupled to heterotrimeric G proteins, and are therefore referred as G protein-coupled receptors (GPCR). They mediate various physiological functions such as vision, taste, calcium, glucose homeostasis and chemotaxis. Chemokines are secretory cytokines able to attract migratory cells. They bind to GPCRs and regulate immune defence, tumour growth, wound healing, allograft rejection, asthma and atherosclerosis. Mechanisms have evolved to fin e-tune and regulate receptor signalling.
Desensitisation consists of inhibiting the response to continuous exposure to the same stimulus; it occurs by uncoupling and inactivation of G protein signalling. The b-arrestins bind to phosphorylated GPCR and physic ally uncouple them from their G proteins, resulting in termination of signalling. Regulators of G protein signalling (RGS) promote desensitisation by accelerating GTP hydrolysis by G proteins, inactivating the signal. Information on how arrestins and RGS act on chemokine receptors and signalling is scarce, and reports are incomplete and/or controversial.
This project aims to study the desensitisation of the chemokine receptors CCR2 and CCR5 in hematopoietic cells using a multidisciplinary approach. We will characterize several receptor-interacting partners using proteomics and determine the temporal and spatial events that occur during CCR signalling and desensitisation by arrestins and RGS19, using total internal reflection microscopy (TIRFM). Using new methods, we will address the questions of how GPCR couple following their heterodimerization, and the functions of RGS in hematopoietic lines.
These studies will provide new insights into the molecular mechanisms of how desensitisation and signalling occur, and will define potential targets for therapeutic intervention. This grant will give me the opportunity to return to the European community of scientists and promote my development as a European experimentalist.
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.
- medical and health sciences basic medicine pharmacology and pharmacy drug discovery
- medical and health sciences clinical medicine pneumology asthma
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- medical and health sciences basic medicine physiology homeostasis
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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.
FP6-2004-MOBILITY-12
See other projects for this call
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.
IRG - Marie Curie actions-International re-integration grants
Coordinator
MADRID
Spain
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.