Objective
Ion channels are proteins composed of a hydrophillic pore that facilitate ion flow across a plasma membrane. This ionic permeability is controlled by a set of essential properties affecting the channel activation and inactivation in response to voltage, ligands, or intracellular second messengers. The focus of the present project proposal, the transient receptor potential vanilloid channel (TRPV5), forms a specific category within the large TRP familiy of ion channels as it comprises a unique high selectivity for calcium ions together with a calcium-dependent inactivation mechanism that is incompletely understood. Detailed analysis of the TRPV5 channel will provide new structural insights into channel gating that can be extrapolated to other TRP channels, as the current knowledge on the TRP protein structure and its impact on the regulation of the channel function is still limited.
The key objective of my project is to deliver the first detailed mechanistic view of TRPV5 by connecting Prof. Cheng’s expertise in structural biology with my biophysical background on TRP channel functioning. The following work packages will be addressed:
1) Channel activation mechanism of TRPV5
Elucidation of the 3D structure of integral TRPV5 by single-particle cryo-EM will provide critical structural and mechanistic insight into calcium-dependent regulation of channel function.
2) Intramolecular regulation of TRPV5
Reconstitution of TRPV5 into lipid nanodiscs and liposomes allows detailed study on lipid regulation and the mechanism of channel inactivation
Taken together, this project focuses on the structure-function analysis of TRPV5, a distinctive calcium-selective TRP channel. The goal is to elucidate the structure of the TRPV5 channel, and to unravel functional domains that are involved in channel function at the mechanistic level. This will ultimately advance our understanding of the molecular differences of activation, ion permeation and gating of TRP channels.
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 chemical sciences inorganic chemistry alkaline earth metals
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences physical sciences optics microscopy electron microscopy
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences molecular biology structural biology
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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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF-GF - Global 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) H2020-MSCA-IF-2016
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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.
6525 XZ Nijmegen
Netherlands
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.