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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.

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

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.
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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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