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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.

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

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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