Objective
"The removal of misfolded and aggregated proteins is essential for cellular homeostasis and organismal health. The accumulation of protein aggregates is associated with several devastating neurodegenerative diseases including Alzheimer’s disease. It has been generally assumed that autophagy has the ability to degrade large aggregates, and considerable efforts are underway to harness this pathway to remove disease-associated aggregates for therapy. However, it is becoming clear that large, solid protein aggregates are poor substrates for autophagy. This is a fundamental conundrum in the basic biology of autophagy, and has posed a serious practical obstacle to these therapeutic efforts.
We have obtained data showing that unlike dynamic, liquid-like autophagy targets, rigid solid aggregates can lock the autophagy machinery into non-productive states. Our data also suggest that there are mechanisms whereby these ""stuck"" states can be avoided or reversed. Thus, the autophagy machinery may contain inherent error correction mechanisms, preventing these states. We will seek such mechanisms and characterize them in enough mechanistic detail to make them actionable therapeutically. Enhancing such mechanisms could enable the clearance of aggregates in aging and the most intractable aging-associated diseases.
DegrAbility will unite complimentary expertise in cellular engineering, in vitro reconstitution and cutting-edge cryo-EM to identify the requirements for cargo to be effectively degraded by autophagy. The project will pinpoint the vulnerabilities of the autophagy machinery and explore ways to address them. We will explore how the dynamic nature of cellular assemblies, like phase-separated condensates, allows for productive machinery assembly, offering new insights into selective autophagy and cell biology in general. Ultimately, this could be a game changer for mechanism-based disease-modifying therapies for the major aging-associated neurodegenerative diseases."
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology homeostasis
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
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.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC-SYG - HORIZON ERC Synergy Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-SyG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1010 WIEN
Austria
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.