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ICaRO SIGNED

Ion Channels and Receptors Operation

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

ICaRO project word cloud

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

reconstituted ligand conformational unliganded functional equilibrium static action activated nucleotide afm differences time binding individual inferences monitored resolution spatiotemporal liberated activation ligands single neuronal recordings homologues calcium modulation snapshots hs channel utilize laser limited speed domains modulates microscopy liganded cyclic structures gating artificial opening understand mechanism conformation imaging data roles closing camp signal modulated precise excitability closed ca2 uv force ion intracellular caged atomic play unknown observe our molecules membranes specialized prokaryotic operation ranging transduction myriad mediated physiological pulses channels

Project "ICaRO" data sheet

The following table provides information about the project.

Coordinator	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Organization address address: RUE DE TOLBIAC 101 city: PARIS postcode: 75654 website: www.inserm.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]
Project website	https://sites.google.com/view/fm4b-lab/group-members/dr-arin-marchesi
Total cost	173˙076 €
EC max contribution	173˙076 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2014
Funding Scheme	MSCA-IF-EF-ST
Starting year	2016
Duration (year-month-day)	from 2016-06-13 to 2018-06-12

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Organization address address: RUE DE TOLBIAC 101 city: PARIS postcode: 75654 website: www.inserm.fr contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	FR (PARIS)	coordinator	173˙076.00

Map

Project 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.

Publications

List of publications.
year	authors and title	journal	last update
2018	Luisa M. R. Napolitano, Arin Marchesi, Alex Rodriguez, Matteo De March, Silvia Onesti, Alessandro Laio, Vincent Torre The permeation mechanism of organic cations through a CNG mimic channel published pages: e1006295, ISSN: 1553-7358, DOI: 10.1371/journal.pcbi.1006295	PLOS Computational Biology 14/8	2019-06-13
2018	Fidan Sumbul, Arin Marchesi, Hirohide Takahashi, Simon Scheuring, Felix Rico High-Speed Force Spectroscopy for Single Protein Unfolding published pages: 243-264, ISSN: , DOI: 10.1007/978-1-4939-8591-3_15	Nanoscale Imaging	2019-06-13
2018	Francesca Zuttion, Lorena Redondo-Morata, Arin Marchesi, Ignacio Casuso High-Resolution and High-Speed Atomic Force Microscope Imaging published pages: 181-200, ISSN: , DOI: 10.1007/978-1-4939-8591-3_11	Nanoscale Imaging	2019-06-13
2018	Fidan Sumbul, Arin Marchesi, Felix Rico History, rare, and multiple events of mechanical unfolding of repeat proteins published pages: 123335, ISSN: 0021-9606, DOI: 10.1063/1.5013259	The Journal of Chemical Physics 148/12	2019-06-13
2018	Arin Marchesi, Xiaolong Gao, Ricardo Adaixo, Jan Rheinberger, Henning Stahlberg, Crina Nimigean, Simon Scheuring An iris diaphragm mechanism to gate a cyclic nucleotide-gated ion channel published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-06414-8	Nature Communications 9/1	2019-04-03

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