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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.

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

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.
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 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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