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Content archived on 2024-06-18

Structural basis of selective autophagy mediated by cargo receptors

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.

Fields of science (EuroSciVoc)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

FP7-PEOPLE-2012-IEF
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Funding Scheme

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MC-IEF - Intra-European Fellowships (IEF)

Coordinator

EUROPEAN MOLECULAR BIOLOGY LABORATORY
EU contribution
€ 161 968,80
Address
Meyerhofstrasse 1
69117 Heidelberg
Germany

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Region
Baden-Württemberg Karlsruhe Heidelberg, Stadtkreis
Activity type
Research Organisations
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Total cost

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