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ATG9_SOLVES_IT SIGNED

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

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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.

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

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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