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AutoClean SIGNED

Cell-free reconstitution of autophagy to dissect molecular mechanisms

Total Cost €

0

EC-Contrib. €

0

Partnership

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 AutoClean project word cloud

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

membrane    pivotal    molecular    longevity    permeabilized    definitive    fusion    progression    extensive    expanding    whilst    central    reconstitutes    organismal    cellular    combat    substrate    nobel    2016    remodelling    activated    devised    yeast    completely    kinase    neurodegenerative    vivo    dissect    twenty    occurs    awarded    biological    mammals    health    assay    cells    first    regulating    promotes    mechanisms    undefined    events    autophagy    individual    autophagic    extensively    mammalian    diseases    protein    vitro    inputs    helps    medicine    carefully    despite    accordingly    lysosomal    digests    elusive    underlie    outputs    prize    conserved    induction    ulk1    downstream    executes    components    identification    origin    functional    atg9    synthetic    plays    mechanistic    membranes    vacuole    cell    thereby    physiology    cancer    recapitulate    activation    reveal    initiating    degradation    atg1    autophagosome    discovered   

Project "AutoClean" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAETSKLINIKUM FREIBURG 

Organization address
address: HUGSTETTER STRASSE 49
city: FREIBURG
postcode: 79106
website: n.a.

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 Germany [DE]
 Total cost 1˙955˙666 €
 EC max contribution 1˙955˙666 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-06-01   to  2023-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM FREIBURG DE (FREIBURG) coordinator 1˙955˙666.00

Map

 Project objective

Autophagy, a lysosomal degradation pathway in which the cell digests its own components, is an essential biological pathway that promotes organismal health and longevity and helps combat cancer and neurodegenerative diseases. Accordingly, the 2016 Nobel Prize in Physiology or Medicine was awarded for research in autophagy. Although autophagy has been extensively studied from yeast to mammals, the molecular events that underlie its induction and progression remain elusive. A highly conserved protein kinase, Atg1, plays a unique and essential role in initiating autophagy, yet despite this pivotal importance it has taken over twenty years for its first downstream target to be discovered. However, whilst our identification of the autophagy related membrane protein Atg9 as the first Atg1 substrate is an important advance, the molecular mechanisms that enable the extensive remodelling of cellular membranes that occurs during autophagy is still completely undefined. A detailed knowledge of the inputs and outputs of the Atg1 kinase will enable us to provide a definitive mechanistic understanding of autophagy. We have devised a novel permeabilized cell assay that reconstitutes the pathway in vitro, allowing us to recapitulate key steps in the autophagic process and thereby determine how the individual steps that lead up to autophagy are controlled. We will use this system to dissect the functional role of Atg1 kinase in autophagosome-vacuole fusion (Objective 1), and to determine the origin of the autophagic membrane and the role of Atg1 in expanding these (Objective 2). To reveal how Atg1/ULK1 kinase is activated in mammalian cells, we will apply the unique and carefully tailored synthetic in vivo approaches that we have recently developed (Objective 3). By focusing on the activation of the Atg1 kinase and the molecular events that it executes, we will be able to explain its central role in regulating the autophagic process and define the mechanistic steps in the pathway.

 Publications

year authors and title journal last update
List of publications.
2018 Levent Bas, Daniel Papinski, Claudine Kraft
Ykt6 mediates autophagosome-vacuole fusion
published pages: e1526006, ISSN: 2372-3556, DOI: 10.1080/23723556.2018.1526006
Molecular & Cellular Oncology 5/6 2020-01-30
2019 David M. Hollenstein, Rubén Gómez-Sánchez, Akif Ciftci, Franziska Kriegenburg, Muriel Mari, Raffaela Torggler, Mariya Licheva, Fulvio Reggiori, Claudine Kraft
Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae
published pages: jcs235002, ISSN: 0021-9533, DOI: 10.1242/jcs.235002
Journal of Cell Science 132/22 2020-01-30
2018 Levent Bas, Daniel Papinski, Mariya Licheva, Raffaela Torggler, Sabrina Rohringer, Martina Schuschnig, Claudine Kraft
Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome–vacuole fusion
published pages: 3656-3669, ISSN: 0021-9525, DOI: 10.1083/jcb.201804028
The Journal of Cell Biology 217/10 2020-01-30
2020 Daniel Poveda-Huertes, Stanka Matic, Adinarayana Marada, Lukas Habernig, Mariya Licheva, Lisa Myketin, Ralf Gilsbach, Sergi Tosal-Castano, Daniel Papinski, Patrycja Mulica, Oliver Kretz, Cansu Kücükköse, Asli Aras Taskin, Lutz Hein, Claudine Kraft, Sabrina Büttner, Chris Meisinger, F.-Nora Vögtle
An Early mtUPR: Redistribution of the Nuclear Transcription Factor Rox1 to Mitochondria Protects against Intramitochondrial Proteotoxic Aggregates
published pages: 180-188.e9, ISSN: 1097-2765, DOI: 10.1016/j.molcel.2019.09.026
Molecular Cell 77/1 2020-01-30
2018 Claudine Kraft, Patricia Boya, Patrice Codogno, Zvulun Elazar, Eeva-Liisa Eskelinen, Judith Farrés, Vladimir Kirkin, Heinz Jungbluth, Ana Martinez, Ole Pless, Charlotte Primard, Tassula Proikas-Cezanne, Anne Simonsen, Fulvio Reggiori
Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy
published pages: 347-351, ISSN: 1554-8627, DOI: 10.1080/15548627.2018.1515532
Autophagy 15/2 2020-01-30
2019 Franziska Kriegenburg, Levent Bas, Jieqiong Gao, Christian Ungermann, Claudine Kraft
The multi-functional SNARE protein Ykt6 in autophagosomal fusion processes
published pages: 639-651, ISSN: 1538-4101, DOI: 10.1080/15384101.2019.1580488
Cell Cycle 18/6-7 2020-01-30

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