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MaSCheNav

Mass Spectrometry-Based Chemoproteomic Profiling of Nav1.7, a Voltage-Gated Sodium Channel

Total Cost €

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EC-Contrib. €

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Partnership

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 MaSCheNav project word cloud

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

fundamental    mutations    ligand    encoding    flux    action    events    propagation    excitable    types    selective    signal    thereby    binding    generation    sodium    mass    expressed    synthesis    transmembrane    complexes    chemical    subtype    conjugation    derives    expressing    functional    na    lines    transmission    unmet    remarkably    lacking    indifference    validated    protein    photoaffinity    painful    ions    syndrome    suffering    peptide    nervous    disease    perfectly    tandem    inhibitors    peripheral    chemoproteomics    membrane    sensing    chronic    translate    patients    structural    once    perceive    function    bioorthogonal    nav1    channels    medical    model    spectrometry    potentials    healthy    modulators    pharmacological    extreme    vgsc    tools    isolate    otherwise    cells    cellular    neurons    nav    voltage    paving    dramatically    nociceptive    safe    treatments    cell    designed    attainment    pain    labeling    gene    solid    congenital    gated    subtypes    patient    interaction    stimuli    channel    probe    vgscs    nine    linked   

Project "MaSCheNav" data sheet

The following table provides information about the project.

Coordinator
IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE 

Organization address
address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ
website: http://www.imperial.ac.uk/

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 United Kingdom [UK]
 Total cost 183˙454 €
 EC max contribution 183˙454 € (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 2015
 Duration (year-month-day) from 2015-11-01   to  2017-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE UK (LONDON) coordinator 183˙454.00

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 Project objective

Chronic pain represents a major unmet medical need which has been linked to changes in voltage-gated sodium channels (VGSCs). These channels are transmembrane protein-complexes with a key-role in signal transmission in excitable cells, such as neurons, and allow the flux of Na ions through the cellular membrane in response to specific stimuli, thus controlling the generation and propagation of action potentials. Nine VGSC subtypes are known to be expressed in different cell types, and among them subtype Nav1.7 is of extreme interest since it is involved in nociceptive processing (pain-sensing) in the peripheral nervous system. Remarkably, patients suffering from congenital indifference to pain syndrome, which derives from loss-of-function mutations of the gene encoding for Nav1.7, have a dramatically reduced ability to perceive painful stimuli, but are otherwise perfectly healthy. Therefore, Nav1.7 has been recognized as an exciting target for pharmacological treatments of pain. However, detailed structural and functional information is lacking, and its attainment represents a fundamental step in the challenging task of finding Nav subtype-selective modulators. Thus, the main focus of my project is to study ligand-binding events with known modulators, thereby paving the way to the design of safe and selective inhibitors. I will develop, by solid phase peptide synthesis, a chemical probe specifically designed to isolate Nav1.7, using a tandem photoaffinity labeling-bioorthogonal conjugation approach. This probe will be applied in model cell lines expressing the channel, in order to study their binding interaction through mass spectrometry-based chemoproteomics. Once these chemical tools are established and validated in the model system, I will translate them to patient-derived cells, in order to study disease-relevant systems.

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