Objective
"GPCRs are involved in a variety of biological and pathological processes ranging from metabolic, neurological and immune system disorders to inflammation. The members of this large family of proteins can be activated by various stimuli including hormones, neurotransmitters, ions, odorants and light. The location of GPCRs on the cell surface and their roles as initiators in many cellular signaling pathways make them predominant drug targets. Around 30% of all drugs on the current therapeutic market function by modulating the activity of GPCRs. One of the most important topics in GPCR field is “biased agonism”: how different ligands induce or stabilise specific conformations of the receptor with distinct pharmacological activity. Equally important is understanding of the basis for ligand selectivity in classes of receptors with identical binding pockets. This selectivity is likely to be determined by the dynamic properties of the pocket or of the ligand entry channel.
NMR spectroscopy can offer structural, dynamic and functional information at atomic resolution into molecular mechanisms of ligand recognition, biased agonism and receptor activation. The aim of the proposed research is to characterise ligand-induced conformational changes in GPCRs and the project will focus on the cannabinoid receptor (CB2), involved in immune response and sensing pain, and is overexpressed in some brain tumors. In particular, I propose a) to label CB2 for NMR analysis based on the successful mutagenesis strategy developed in the host laboratory to produce stabilised recombinant receptors for X-ray crystallography; b) to obtain a dynamic view of the conformational changes in CB2 induced by ligand binding; c) to compare the conformational changes causes by a spectrum of ligands with different activities, from antagonists to agonists.
In addition, this general approach could also be extended to other “difficult” membrane proteins."
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 earth and related environmental sciences geology mineralogy crystallography
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- natural sciences physical sciences optics spectroscopy absorption spectroscopy
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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-2011-IEF
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.
Coordinator
5232 VILLIGEN PSI
Switzerland
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.