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DYNACOTINE SIGNED

Signal transduction and allosteric modulation of nicotinic acetylcholine receptors:from ion channel electrophysiology to atomic 3D structures

Total Cost €

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EC-Contrib. €

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Partnership

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 DYNACOTINE project word cloud

Explore the words cloud of the DYNACOTINE project. It provides you a very rough idea of what is the project "DYNACOTINE" about.

structural    alpha    starting    course    pharmacology    resolution    receptors    conformations    electrophysiology    gained    nachr    domain    plasticity    biology    centered    dynamics    functionally    channels    technique    routes    protein       3d    transmembrane    gated    conformational    shape    combines    wp3    adopting    ligand    acetylcholine    concomitant    wp2    expressed    elusive    heteromeric    channel    original    cell    mediate    unanticipated    insights    quenching    allosteric    cognition    wp1    silico    acting    innovative    players    crosstalk    transmission    function    homomeric    motions    membrane    nachrs    single    electrophysiological    structures    proteins    time    opening    therapeutics    purified    date    functions    solved    nicotinic    biochemistry    therapeutic    modeling    neuronal    mechanisms    promises    underlying    multiple    modulators    pharmacological    dissecting    lipids    revealed    display    requirement    drug    ion    fluorescence    hold    cells    follow    physiological    molecular    transitions    docking    modulation    beta    synaptic    multidisciplinary    fundamental    reward    primarily    brain    structure   

Project "DYNACOTINE" data sheet

The following table provides information about the project.

Coordinator
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS 

Organization address
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 2˙282˙105 €
 EC max contribution 2˙282˙105 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2019
 Duration (year-month-day) from 2019-01-01   to  2023-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS FR (PARIS) coordinator 2˙282˙105.00

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 Project objective

Nicotinic acetylcholine receptors (nAChRs) mediate neuronal synaptic transmission and modulation. They contribute to higher brain functions such as cognition and reward and are important drug targets. Recent studies have revealed that these acetylcholine-gated ion channels display an unanticipated conformational plasticity, adopting multiple allosteric states that shape the time course of their electrophysiological response. To date, a single nAChR structure has been solved at high resolution, and our understanding of the conformational transitions remains so far elusive. To address this challenge, we propose to develop a top-down approach starting from the study of the conformational transitions of nAChRs functionally expressed in cells, and then dissecting the molecular mechanisms on purified proteins. In WP1, we will develop an innovative fluorescence quenching approach to follow the protein motions concomitant with channel opening at the cell membrane. In WP2, we will further exploit this technique on purified proteins, to study the role/requirement of lipids, and their pharmacological crosstalk with allosteric modulators acting at the transmembrane domain. In WP3, the gained knowledge will open original routes to solve 3D structures of nAChRs, in novel conformations and in complex with allosteric modulators. The research will be centered on the major brain nAChRs, primarily the homomeric α7 and also the heteromeric α4β2 nAChRs that are major physiological players and key potential therapeutic targets. This multidisciplinary project combines electrophysiology, fluorescence, pharmacology, membrane protein biochemistry and structural biology, together with in silico modeling, molecular dynamics and ligand docking. The results will provide fundamental insights into the allosteric mechanisms underlying both nAChR function and its modulation by allosteric modulators that hold promises in therapeutics.

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The information about "DYNACOTINE" are provided by the European Opendata Portal: CORDIS opendata.

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