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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.

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

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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