Project description
Unravelling the early stages of protein clustering in Parkinson’s disease
Understanding how Parkinson’s disease (PD) develops is crucial to finding better treatments. A key factor in this disease is the accumulation of protein clumps in neuronal brain cells that mainly involve a protein called alpha-synuclein (α-syn). According to research, these clumps form through a process called liquid-liquid phase separation (LLPS), where proteins temporarily cluster together. However, the early steps of this process are not well understood because current tools cannot capture these events quickly. With the support of the Marie Skłodowska-Curie Actions programme, the ELSa project will use cutting-edge X-ray techniques to observe LLPS in real time along with computer simulations for better molecular resolution. The proposed research could reveal how α-syn clumps form, offering new strategies for early PD detection and treatment.
Objective
Parkinson's disease (PD) affects 10 million people worldwide and is characterized by the abnormal accumulation of protein aggregates in neuronal cells. Such aggregates are mainly composed of an intrinsically disordered protein called alpha-synuclein (α-syn). Recent evidence suggests that the nucleation event driving α-syn aggregation might be initiated by liquid-liquid phase separation (LLPS). Due to a lack of techniques able to look at the early-stage LLPS the link between α-syn aggregation and LLPS is missing. Current strategies mainly focus on temporal scales where LLPS is already in place (seconds, minutes, hours) and hence there is the need to access the temporal scale of sub-second to shed light on this mechanism. The goal of Elsα (Early-stage LLPS of α-syn) is to elucidate the molecular mechanisms underlying α-syn LLPS and disentangle the contributions at play. To this purpose, I will use an innovative multi-disciplinary approach that combines a cutting-edge time-resolved small-angle X-ray scattering technique with computer simulations. The first enables real-time investigation of LLPS formation with an unprecedented temporal resolution of up to milliseconds. The second will complement the experimental outcomes with a molecular view of the phenomena. By integrating experimental and computational methods, I will identify key factors initiating α-syn LLPS, disentangle their contributions, construct comprehensive phase diagrams for α-syn under various conditions, and eventually unravel the early-stage molecular events in LLPS formation. This research promises to significantly advance our understanding of PD pathogenesis, potentially leading to novel early-phase screening methods and more effective therapeutic strategies for PD neurodegenerative disorder. Further, It will lead to high-impact publications that will increase my visibility in the scientific community boosting my career on the path to becoming a young group leader.
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 neurology parkinson
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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)
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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.
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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
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(opens in new window) HORIZON-MSCA-2024-PF-01
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1165 KOBENHAVN
Denmark
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