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ATG9_SOLVES_IT SIGNED

In vitro high resolution reconstitution of autophagosome nucleation and expansion catalyzed byATG9

Total Cost €

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EC-Contrib. €

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Partnership

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 ATG9_SOLVES_IT project word cloud

Explore the words cloud of the ATG9_SOLVES_IT project. It provides you a very rough idea of what is the project "ATG9_SOLVES_IT" about.

tomography    components    vitro    dissection    lastly    ampk    neurodegeneration    homeostasis    proteins    interact    proteome    resident    tools    form    acutely    traffics    crucially    vesicle    expand    disease    unknown    biochemically    functional    lipids    recruitment    reconstitution    protein    autophagy    employ    signaling    manipulation    vesicles    regulate    endocytic    identification    property    em    spectrometry    mediated    deregulation    autophagosomes    atg9    correlative    modulate    cryo    occurs    torc1    starvation    initiating    generation    quantitative    translational    cargo    molecular    initiates    composition    function    membranes    uncover    proximity    cell    rapid    nucleation    nucleate    expansion    tested    secretory    autophagosome    lysosomal    acid    regulators    conserved    functions    atg    mass    amino    aging    light    transmembrane    assayed    optogenetic    immunity    biotinylation    resolution    reconstituted    cancer    survival    membrane    energy    infection    microscopy    selective    master    initiation    electron    accessory    therapies    implicated   

Project "ATG9_SOLVES_IT" data sheet

The following table provides information about the project.

Coordinator
THE FRANCIS CRICK INSTITUTE LIMITED 

Organization address
address: 1 MIDLAND ROAD
city: LONDON
postcode: NW1 1AT
website: www.crick.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 2˙121˙055 €
 EC max contribution 2˙121˙055 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2023-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE FRANCIS CRICK INSTITUTE LIMITED UK (LONDON) coordinator 2˙121˙055.00

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 Project objective

Autophagy is a conserved, lysosomal-mediated pathway required for cell homeostasis and survival. It is controlled by the master regulators of energy (AMPK) and growth (TORC1) and mediated by the ATG (autophagy) proteins. Deregulation of autophagy is implicated in cancer, immunity, infection, aging and neurodegeneration. Autophagosomes form and expand using membranes from the secretory and endocytic pathways but how this occurs is not understood. ATG9, the only transmembrane ATG protein traffics through the cell in vesicles, and is essential for rapid initiation and expansion of the membranes which form the autophagosome. Crucially, how ATG9 functions is unknown. I will determine how ATG9 initiates the formation and expansion of the autophagosome by amino acid starvation through a molecular dissection of proteins resident in ATG9 vesicles which modulate the composition and property of the initiating membrane. I will employ high resolution light and electron microscopy to characterize the nucleation of the autophagosome, proximity-specific biotinylation and quantitative Mass Spectrometry to uncover the proteome required for the function of the ATG9, and optogenetic tools to acutely regulate signaling lipids. Lastly, with our tools and knowledge I will develop an in vitro reconstitution system to define at a molecular level how ATG9 vesicle proteins, membranes that interact with ATG9 vesicles, and other accessory ATG components nucleate and form an autophagosome. In vitro reconstitution of autophagosomes will be assayed biochemically, and by correlative light and cryo-EM and cryo-EM tomography, while functional reconstitution of autophagy will be tested by selective cargo recruitment. The development of a reconstituted system and identification proteins and lipids which are key components for autophagosome formation will provide a means to identify a new generation of targets for translational work leading to manipulation of autophagy for disease related therapies.

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