Objective
A common characteristic in many neurodegenerative diseases (NDs) is the presence of disordered proteins that form toxic aggregates. In Huntington’s disease (HD), expanded polyQ tracts on Huntingtin (Htt) lead to the formation of aggregates, which affects many cellular functions, eventually resulting in cell death. Heat Shock Response (HSR) is a protective mechanism that facilitates (among other functions) the clearance of protein aggregates. Paradoxically, HSR becomes impaired in HD. The fact that early Htt aggregates, prior to becoming severely aggregated or toxic, fail to trigger HSR indicates that this impairment likely occurs early in the HD pathogenesis. The molecular mechanism underlining the HSR impairment in HD remains elusive. The aim of UnFearHD is to unravel the mechanism that links Htt aggregation with HSR impairment in early stages of HD.
Several lines of evidence indicate that disordered proteins, having the ability to phase separate, may directly regulate translation and transcription, as shown for biomolecular condensates. Our hypothesis is that aggregation-prone Htt alters the early HD proteome composition in a way that impacts the HSR, by directly interacting with RNA and DNA. To explore our hypothesis, we will employ C. elegans strains engineered for inducible Htt expression and combine unbiased omics to a) directly interrogate the Htt interactions with RNAs and DNAs, using a UV-based crosslinking and immunoprecipitation (CLIP) and b) understand the consequences of such interactions at proteome level, using a bioorthogonal non-canonical amino acid tagging (BONCAT). The UnfearHD project will enable the establishment, for the first time, of a direct association between Htt aggregation and HSR impairment, which is detrimental for HD progression. The findings will stretch beyond the scope of UnfearHD as the combination of protein aggregation and HSR impairment is detrimental for other NDs but also seems to constitutes a universal mechanism of ageing.
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 proteomics
- natural sciences biological sciences genetics DNA
- natural sciences biological sciences genetics RNA
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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.4.1 - Widening participation and spreading excellence
MAIN PROGRAMME
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HORIZON.4.1.5 - Fostering brain circulation of researchers and excellence initiatives
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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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) HORIZON-WIDERA-2022-TALENTS-04
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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.
70 013 IRAKLEIO
Greece
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.