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3D NKCC1 SIGNED

Interdisciplinary approach to characterize the structure and the ion transport mechanism of NKCC1, a key target for brain disorders.

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 3D NKCC1 project word cloud

Explore the words cloud of the 3D NKCC1 project. It provides you a very rough idea of what is the project "3D NKCC1" about.

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Project "3D NKCC1" data sheet

The following table provides information about the project.

Coordinator
FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA 

Organization address
address: VIA MOREGO 30
city: GENOVA
postcode: 16163
website: www.iit.it

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 Italy [IT]
 Total cost 168˙369 €
 EC max contribution 168˙369 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2018
 Funding Scheme MSCA-IF-GF
 Starting year 2019
 Duration (year-month-day) from 2019-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA IT (GENOVA) coordinator 168˙369.00
2    BAYLOR COLLEGE OF MEDICINE US (HOUSTON TX) partner 0.00

Map

 Project objective

Neurodevelopmental disorders affect millions of children in Europe and worldwide. A large body of literature indicates that inhibitory GABAergic transmission thorough Cl-permeable GABAA receptors is defective in many of these disorders. However, effective pharmaceutical treatments are still needed. There is increasing scientific evidence that varying the intracellular Cl concentration is one of the more physiological and effective ways to modulate GABAAergic transmission. This concentration is mainly established by the Cl importer NKCC1 and the Cl exporter KCC2. Importantly, the NKCC1/KCC2 ratio is defective in several brain disorders. Moreover, NKCC1 inhibition by the FDA-approved diuretic bumetanide rescues many symptoms in animal models. These findings have already led to clinical studies of bumetanide to treat a broad range of brain disorders. However, this requires chronic treatment, which poses serious issues for drug compliance, given the diuretic effect of bumetanide caused by the inhibition of the kidney-specific Cl transporter NKCC2. Crucially, these issues could be solved by selective NKCC1 inhibitors, which would have no diuretic effect. Yet there is still very little knowledge of the structure-function relationship of NKCC1 in terms of ion transportation and how bumetanide acts on NKCC1. The main goal of this fellowship is to resolve NKCC1’s structure using X-Ray crystallography and/or cryo-electron microscopy. This effort will be coupled to the functional characterization of NKCC1 using in vitro and in silico approaches. The fellow will thus integrate her research skills with key expertise in the structural and molecular biology of ion transporters, allowing her to grow into an independent group leader. Ultimately, this project will provide unprecedented insights into the structure-function relationships of NKCC1 in terms of ion transportation. This will critically accelerate the discovery of new and urgently needed drugs for brain disorders.

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The information about "3D NKCC1" are provided by the European Opendata Portal: CORDIS opendata.

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