Objective
Dysfunction of protein Tau is the main cause of dementia. Dementia associates with synaptic failure and sleep disturbances, but their connection remains elusive. In dementia, Tau becomes hyperphosphorylated (p-Tau) causing synaptic loss. Temperature fluctuations also associate with Tau phosphorylation, for example in hibernating animals. Intriguingly, my work demonstrates that brain temperature decreases during sleep, and further evidence suggests there are Tau-sites phosphorylated during sleep. My hypothesis is that sleep (and temperature)-induced Tau phosphorylation drives synaptic plasticity changes during sleep. To investigate this, I will map the dynamic changes in p-Tau during sleep and then delve into the mechanisms by mimicking brain temperature changes that naturally occur during sleep in human-induced neurons and mouse primary neurons. Employing genome engineering, I will interfere with p-Tau during sleep in mice in vivo and evaluate its impact on sleep, sleep-dependent synaptic plasticity and hippocampal long-term potentiation. This research challenges the notion that p-Tau solely drives disease progression, exploring a physiological function for p-Tau in regulating synaptic plasticity during sleep. The result of this project can challenge our understanding of Tau's function and open a new therapeutic avenue: the development of sleep-wake mechanisms to reverse the pathological p-Tau state observed in dementia. With my host lab's prior track record of uncovering critical insights into Tau-induced synaptic dysfunction, it stands as the perfect platform to tackle these questions. Additionally, I find myself in an ideal position, armed with exciting preliminary data that bolsters the validity of this proposal, and a robust technical and scientific background that empowers me to embark on this ambitious research journey. The plan I propose brings us closer to breakthroughs in effective dementia treatments.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology dementia
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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
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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.
9052 ZWIJNAARDE - GENT
Belgium
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.