Project description
Potential new therapeutic target for Alzheimer’s disease
Despite the high incidence of Alzheimer’s disease, there are limited effective treatments available. With the support of the Marie Skłodowska-Curie Actions programme, the PhaSeAD project will investigate a protein called c-Abl, which may play a key role in how the disease develops. Researchers will study how c-Abl behaves inside small liquid-like droplets that form inside cells, a process known as liquid-liquid phase separation (LLPS), which is increasingly linked to neurodegeneration. By examining how c-Abl interacts with important neuronal proteins such as Tau, the project aims to determine its role in disease. Advanced imaging and biochemical tests will help reveal how c-Abl affects the cell’s internal scaffolding and overall neuron health.
Objective
Neurodegenerative diseases like Alzheimer's disease (AD) are a major global health concern, affecting millions and placing significant economic burdens on healthcare systems. Despite advancements in understanding AD pathogenesis, effective treatments remain elusive. PhaSeAD (Phase separation in Alzheimer's disease and Phase-separated c-Abl dynamics) aims to explore the role of the c-Abl protein kinase in AD pathogenesis, focusing on its interaction with liquid-liquid phase separation (LLPS). Objectives include understanding c-Abl phosphorylation specificity using NMR spectroscopy to study its interaction with substrates Tau and PSD-95, providing insights into c-Abl's substrate specificity and phosphorylation selectivity. Additionally, we will explore c-Abl function within LLPS droplets using biochemical assays like ITC and kinase assays to assess its activity inside and outside LLPS droplets. Fluorescence microscopy techniques like FRAP and FCS will visualize and quantify c-Abl dynamics within LLPS droplets and its interaction with other LLPS components. Furthermore, we will investigate the role of c-Abl and LLPS in regulating cytoskeletal dynamics, crucial for neuronal function and disrupted in AD. High-resolution microscopy techniques, including super-resolution and electron microscopy, will visualize and quantify the impact of c-Abl and LLPS on cytoskeletal assembly and organization. Live-cell imaging techniques will assess their impact on neuronal morphology and function. Expected outcomes include a comprehensive understanding of c-Abl's behavior within LLPS droplets, its impact on Tau and PSD-95 phosphorylation, and its regulatory role in cytoskeletal homeostasis. These findings will enhance our understanding of c-Abl's involvement in AD pathogenesis and may lead to novel therapeutic targets for developing effective treatments for AD and other neurodegenerative diseases.
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 physical sciences optics spectroscopy
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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)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-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.
53127 Bonn
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.