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Autophagy in vitro SIGNED

Reconstituting Autophagosome Biogenesis in vitro

Total Cost €

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EC-Contrib. €

0

Partnership

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 Autophagy in vitro project word cloud

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

cells    coordinate    ub    differences    shaped    protein    degradation    cultured    possess    confocal    reconstituted    tested    structure    catabolic    engulf    model    pathophysiology    effort    cargo    capture    superfluous    humans    organization    unravel    stresses    homologs    forms    found    insights    expansion    isolation    belief    interconnected    atg8    neurodegenerative    membrane    microscopy    functional    autophagosomes    cytotoxic    starvation    function    precursor    unselectively    human    recombinant    surrounded    cancer    atg5    vivo    membranes    electron    atg16    serves    atg    productive    vegetative    components    coordinates    double    revealing    autoimmune    labeled    exclusive    vitro    atomic    expands    aggregates    sealing    atg16l1    fluorescent    organelles    larger    scaffold    conjugating    mechanistic    mutually    autophagy    ubiquitin    cup    lysosomes    quality    spatiotemporal    structural    synthetic    induces    atg12    yeast    seven    gives    diseases    tirf    material    cytoplasmic    force    canonical    proteins    tecpr1    delivers    conjugation    damaged    variants   

Project "Autophagy in vitro" data sheet

The following table provides information about the project.

Coordinator
INSTITUT PASTEUR 

Organization address
address: RUE DU DOCTEUR ROUX 25-28
city: PARIS CEDEX 15
postcode: 75724
website: http://www.pasteur.fr

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 France [FR]
 Total cost 1˙499˙726 €
 EC max contribution 1˙499˙726 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-04-01   to  2020-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT PASTEUR FR (PARIS CEDEX 15) coordinator 1˙185˙057.00
2    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) participant 314˙668.00

Map

 Project objective

Autophagy is a catabolic pathway that delivers cytoplasmic material to lysosomes for degradation. Under vegetative conditions, the pathway serves as quality control system, specifically targeting damaged or superfluous organelles and protein-aggregates. Cytotoxic stresses and starvation, however, induces the formation of larger autophagosomes that capture cargo unselectively. Autophagosomes are being generated from a cup-shaped precursor membrane, the isolation membrane, which expands to engulf cytoplasmic components. Sealing of this structure gives rise to the double-membrane surrounded autophagosomes. Two interconnected ubiquitin (Ub)-like conjugation systems coordinate the expansion of autophagosomes by conjugating the autophagy related (Atg)-protein Atg8 to the isolation membrane. In an effort to unravel the function of Atg8, we reconstituted the system on model membranes in vitro and found that Atg8 forms together with the Atg12–Atg5-Atg16 complex a membrane scaffold which is required for productive autophagy in yeast. Humans possess seven Atg8-homologs and two mutually exclusive Atg16-variants. Here, we propose to investigate the function of the human Ub-like conjugation system using a fully reconstituted in vitro system. The spatiotemporal organization of recombinant fluorescent-labeled proteins with synthetic model membranes will be investigated using confocal and TIRF-microscopy. Structural information will be obtained by atomic force and electron microscopy. Mechanistic insights, obtained from the in vitro work, will be tested in vivo in cultured human cells. We belief that revealing 1) the function of the human Ub-like conjugation system in autophagy, 2) the functional differences of Atg8-homologs and the two Atg16-variants Atg16L1 and TECPR1 and 3) how Atg16L1 coordinates non-canonical autophagy will provide essential insights into the pathophysiology of cancer, neurodegenerative, and autoimmune diseases.

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