Objective
Aggregation of RNA binding proteins (RBPs) is a pathological hallmark of neurodegenerative pathologies such as Amyotrophic Lateral Sclerosis. The mechanism leading to RBP aggregation relies on the ability of these proteins to transition into membrane-less compartments such as the stress granules (SG) whose formation is normally regulated in physiological conditions. Yet, as RBPs are intrinsically prone to coalesce in large assemblies, their accumulation, when unregulated, can lead to cell toxicity. While the effects of amino acid mutations on RBP aggregation have been extensively investigated, a large amount of evidence indicates that nucleotide variants in untranslated regions (UTRs) can strongly impact RBP expression by altering the interactions with specific regulatory proteins. UTRs provide a platform where multiple RBPs bind to orchestrate post-transcriptional regulation. I envision that UTRs, by directing contacting specific protein networks are crucial in aggregate formation and that alteration of their interactomesdue to disease-linked mutationscould impact the propensity to form SG and other assemblies. The main objective of UNDERPIN is to reveal interactions in regulatory regions of RBPs and to understand their effects on phase separation in physiology and pathology. Firstly, I plan to investigate the effects of disease-linked mutations on UTRs of RNAs encoding RBPs by large-scale predictions of UTR-RBP interactors. Secondly, interactions between RBP and selected UTRs, with and without disease-linked mutations, will be revealed in human cells by RNA-protein interaction detection experimental method RaPID. Finally, the biological implications of UTR-mediated recruitment of RBPs will be deciphered providing molecular details on how UTRs and RBPs promote the formation of aggregates. Successful completion of this project will not only lead to new insights into RBP biology, but will also pave the way to understand early events of neurodegeneration.
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
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
- medical and health sciences basic medicine physiology
- 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.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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-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-MSCA-2021-PF-01
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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.
16163 GENOVA
Italy
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.