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MYOCLEM SIGNED

Elucidating the Molecular Mechanism of Myoblast Fusion in Vertebrates

Total Cost €

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EC-Contrib. €

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Partnership

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 MYOCLEM project word cloud

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

membrane    fusion    electron    fundamental    tissues    visualizing    subsequently    strategy    primary    view    fusogenic    quantitative    radically    live    combination    until    tomography    gap    underlying    events    myofibers    muscle    mirrored    mechanism    sites    striking    cryo    clem    organization    myoblasts    dissect    regeneration    biophysical    model    sensitivity    physiological    dynamic    data    resolution    vertebrate    assembles    et    driving    strategies    remodels    correlative    deriving    vital    skeletal    ultrastructure    plasma    resolve    form    diseases    assembly    ubiquitous    cellular    function    poorly    remodeling    generate    multinucleated    light    machinery    phenomenon    signals    shape    localize    architecture    precision    remodeled    cell    treat    averaging    molecular    fluorescent    structure    source    myoblast    samples    synergetic    revealing    biochemistry    imaging    fill    situ    ultrastructural    synapse    microscopy    experimental    em    occurs    subtomogram    3d   

Project "MYOCLEM" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 1˙500˙000 €
 EC max contribution 1˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2019-STG
 Funding Scheme ERC-STG
 Starting year 2019
 Duration (year-month-day) from 2019-11-01   to  2024-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 1˙500˙000.00

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 Project objective

Cell-to-cell fusion is a ubiquitous phenomenon essential for the physiological function of numerous tissues. A striking example is the fusion of myoblasts to form multinucleated myofibers during skeletal muscle development and regeneration. During myoblast fusion, membrane architecture must be radically remodeled. Yet, how membrane remodeling occurs on the molecular level is poorly understood as, until now, there was no approach available for visualizing dynamic changes in the cellular ultrastructure and the organization of the fusion machinery in situ. To fill this gap, we have developed correlative light and 3D electron microscopy (CLEM) methods that allow us to identify fluorescent signals within EM samples with high sensitivity and subsequently localize the source of these signals with high precision. In this proposal, we will apply these methods in combination with live-cell imaging, biochemistry and cryo-electron tomography (ET) to deliver fundamental knowledge about the mechanism of myoblast fusion. Our specific aims are: Aim 1: To resolve the molecular and ultrastructural events underlying cell fusion, by revealing how plasma membrane architecture is remodeled at sites of fusion using 3D EM. Aim 2: To dissect the mechanism driving membrane remodeling during fusion, by visualizing how the fusion machinery assembles at sites of fusion and how its assembly is mirrored by changes in membrane shape, using biochemistry and live-cell imaging. Aim 3: To determine the structure of the fusion machinery in situ, by using cryo-ET and subtomogram averaging. Our synergetic experimental strategy will generate a quantitative, dynamic high-resolution view of the fusogenic synapse of vertebrate muscle, revealing how the fusion machinery remodels the plasma membrane at sites of fusion. These data are vital for deriving a biophysical model of myoblast fusion, understanding the general mechanism of cell fusion, and developing strategies to treat primary muscle diseases.

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