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Ion Channels and Receptors Operation

Objective

Our understanding of ion channel operation is limited to inferences based on functional data and to static snapshots of their structures where they are available. Cyclic nucleotide-modulated channels and calcium-activated K+ channels play crucial roles in a myriad of physiological processes ranging from signal transduction to neuronal excitability. The binding of ligands to specialized intracellular domains modulates the opening/closing (gating) equilibrium of these channels. Both the high resolution structures - in open and closed conformation - of these channels and the precise mechanism of ligand-mediated channel activation are unknown. The present proposal aims to understand the mechanism of ion channel modulation by ligands. To accomplish this goal we will utilize prokaryotic homologues of these channels reconstituted in artificial membranes. High-speed atomic force microscopy (HS-AFM) will allow us to directly observe individual ion channel molecules in action at high spatiotemporal resolution and in physiological conditions. Through UV-laser pulses caged ligands (caged-Ca2+ or caged-cAMP) will be liberated during HS-AFM imaging and the conformational changes associated to ligand binding monitored in real time. Differences between liganded and unliganded channel structures will provide insight into the mechanism of ligand gating. The obtained data will be compared to single channel current recordings under comparable conditions.

Fields of science (EuroSciVoc)

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Programme(s)

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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.

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.

MSCA-IF-EF-ST - Standard EF

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Call for proposal

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

(opens in new window) H2020-MSCA-IF-2014

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Coordinator

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

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.

€ 173 076,00
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.

€ 173 076,00
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