Project description
Advancing drug discovery for kidney-related diseases
Our kidneys control the amount of water and salt in the body and hence how much urine we produce. The hormone arginine vasopressin (AVP) plays a key physiological role in the ability of kidneys to reabsorb water and maintain body water homeostasis. This is mediated through the binding of AVP to the V2 receptor (V2R) on kidney collecting ducts. Funded by the Marie Skłodowska-Curie Actions programme, the 3D-V2R project aims to structurally characterise the binding of AVP to V2R and provide insight into the downstream events of receptor activation. Given the importance of V2R as a therapeutic target, project results have important clinical applications.
Objective
G protein-coupled receptors (GPCR) are the largest superfamily of cell surface signaling membrane proteins and the targets of 30% of marketed drugs for many human diseases. They respond to diverse extracellular stimuli by transmitting the signal across the membrane and activating a number of intracellular signaling pathways. To sense these stimuli and couple to signaling partners such as G proteins, these transmembrane domains have a high conformational flexibility, representing a challenge for structure determination. Both improvements of GPCR expression and purification, and the cryo-EM revolution have led to structurally characterized GPCR to better understand these signaling key players. However, defining active states of a given receptor is still a difficult challenge that led to success only for a dozen different GPCR. This project focus on the characterization of different states of the arginine vasopressin (AVP) V2 receptor (V2R). The V2R is considered as a receptor model for small peptides and hormones and is a crucial therapeutic target. The atomic resolution data will contribute to a better knowledge of the V2R transmembrane signaling. The comparison of the different active states of the V2R to the inactive state of V2R will provide key information for deciphering the molecular events leading to receptor activation. Then, blocking the V2R with antagonists is a validated therapeutic avenue for two unmet medical needs, hyponatremia and autosomal dominant polycystic kidney disease. V2R interacts not only with Gs protein but also with arrestins, the development of biased agonists that selectively activate or inhibit one signaling cascade among all triggered by the natural hormone is also a very promising therapeutic line. Keeping in mind the interest of antagonists/inverse agonists and biased agonists of the V2R for human health, we expect our data will have a major impact on drug discovery, in addition to be of general interest in terms of scientific impact.
Fields of science (EuroSciVoc)
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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.
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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.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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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.
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.
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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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.
(opens in new window) HORIZON-MSCA-2021-PF-01
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75794 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.