AUTOCARGO

Structural basis of selective autophagy mediated by cargo receptors

Coordinatore	EUROPEAN MOLECULAR BIOLOGY LABORATORY    more  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Ms. Nome: Jillian Cognome: Rowe Email: send email Telefono: 4962210000000 Fax: +49 6221 3878575
Nazionalità Coordinatore	Germany [DE]
Totale costo	161˙968 €
EC contributo	161˙968 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-06-01   -   2016-05-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	EUROPEAN MOLECULAR BIOLOGY LABORATORY  Organization address address: Meyerhofstrasse 1 city: HEIDELBERG postcode: 69117 contact info Titolo: Ms. Nome: Jillian Cognome: Rowe Email: send email Telefono: 4962210000000 Fax: +49 6221 3878575	DE (HEIDELBERG)	coordinator	161˙968.80

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 Obiettivo del progetto (Objective)

'Autophagy is a bulk cellular degradation pathway in which double-membrane vesicles engulfe large and long-lived cytoplasmic structures and target them to lysosomal compartments. Employing an integrated structural biology approach using single-particle cryo-EM and X-ray crystallography, this proposal aims to elucidate the structural details by which the autophagosomal recognition machinery identifies and assembles its cargo for targeting to autophagosomes. It has recently become apparent that selective autophagy requires specific receptors that recognize and recruit defined cargo into molecular assemblies and target them for autophagosomal degradation. Dysfunction of this process is implicated in a number of important human pathologies, such as cancer, neurodegeneration and myopathies. A precise understanding of the molecular mechanisms underlying selective autophagy requires the structural characterization of the molecular complexes involved in this process. First, the ultrastructural architecture of homo-oligomeric receptor assemblies will be established. Second, the structural organization of cargo-receptor complexes will be defined for a hetero-oligomeric, mechanosensitive model complex involved in muscle homeostasis using a combination of cryo-EM and X-ray crystallography. Third, oligomeric changes of cargo-receptor assemblies will be related to cellular function. In its aim to establish a multi-resolution view on the molecular principles of selective autophagy, this proposal has the potential to fundamentally advance our current understanding of this important degradation pathway.'