Objective
Loss of protein homeostasis (proteostasis) is a critical feature of aging and a major driver of neurodegenerative diseases such as Huntington’s and ALS. A key guardian of proteome integrity is ubiquitination, a versatile post-translational modification that controls protein degradation, localization, and activity. Remarkably, disease-associated protein aggregates are ubiquitin-positive, yet how age-related remodeling of ubiquitination disrupts proteostasis and accelerates functional decline remains unknown. My recent work revealed that aging causes a global remodeling of the ubiquitin landscape. Particularly, age-dependent alterations in ubiquitin-mediated proteasomal degradation determine both lifespan and neurodegeneration in C. elegans. These findings uncover ubiquitination as a molecular determinant of aging, but the underlying mechanisms and systemic consequences are unexplored. This project will establish the comprehensive framework for ubiquitination in aging and neurodegeneration. We will (1) define how altered ubiquitination impacts autophagy and protein aggregation, (2) unravel the intracellular and inter-tissue mechanisms that regulate ubiquitin signaling across lifespan, and (3) dissect how ubiquitination coordinates crosstalk among distinct aging hallmarks, including genomic instability and proteostasis, using premature aging syndromes as a paradigm. By combining state-of-the-art proteomics, C. elegans genetics, and patient-derived iPSC models, this research will uncover fundamental principles by which ubiquitin signaling shapes proteome integrity, organismal homeostasis, and longevity. Additionally, this project will open new avenues for therapeutic intervention against aging and neurodegenerative diseases.
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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)
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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 - HORIZON ERC 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-2026-STG
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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.
60323 Frankfurt Am Main
Germany
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.