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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.

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

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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