Objective
Neurodegenerative disorders are the leading cause of physical and cognitive disability, currently affecting ~15% population worldwide with estimated global cost of healthcare accosiated with them expected to at least double in the next 20 years. Five most common neurodegenerative diseases, including ALS and FTD, are linked to formation of protein deposits in patient tissues and are currently without treatment options that would prevent or alter the disease progression. ALS and FTD pathology is characterised by accumulation and formation of insoluble protein deposits formed by proteins, like TDP-43, FUS and DAXX. These proteins undergo liquid-liquid phase transition (LLPS) in cells forming non-membrane bound organelles, which are important in RNA processing and stress responses of cells but their dysregulation acts a precursor to protein fibrillation. In this project we will, therefore, combine traditional biophysical approaches with modern molecular dynamics simulations and solution state nuclear magnetic resonance to discern this complex behaviour leading to LLPS, and gain molecular insight into its onset. Major outcomes of the project are (1) Develop the necessary simulation tools by reparametrizing currently available force fields using experimental data; (2) Apply the simulation tool and analytical methods to interactions between oligonucleotides and ions with proteins and compare results to experimental data; (3) Map phases and coacervation of DAXX in the presence of nucleotides and ions; (4) identify residues crucial for fibrillation and determine their role in cellular LLPS; (5) Apply high-throughput virtual screening to design proteins aggregation breaking ligands with therapeutic potential Outcomes of this project will importantly enhance our understanding at a mechanistic level, the role of these factors in promoting LLPS in cell biology.
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.
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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-2023-PF-01
See all projects funded under this callCoordinator
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.
2000 Maribor
Slovenia
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.