Objective
Alzheimer’s disease (AD) is the most common cause of dementia, affecting over 57 million people worldwide. It is a progressive, fatal neurodegenerative disorder with no curative treatments, imposing a major burden on patients, families, healthcare systems, and society.
AD is marked by amyloid-beta (Aβ) plaque accumulation. Microglia, the brain’s immune cells, attempt to degrade these aggregates through their lysosomes, but this process is often inefficient and may even contribute to Aβ spread.
I hypothesize that Aβ pathology reshapes the proteome of human microglial lysosomes, impairing their function and promoting disease progression. To date, no study has systematically mapped how the human microglial lysosomal proteome changes dynamically in response to Aβ pathology.
To address this knowledge gap, I will use a xenotransplantation model in which human iPSC-derived microglia are engrafted into either healthy or Aβ-accumulating mouse brains. TurboID proximity labeling will enable in vivo profiling of lysosomal proteins altered by Aβ pathology. To test the functional consequences of this alteration, I will employ a targeted CRISPR/Cas9 screen in human microglia-neuron-astrocyte tri-cultures, identifying genes whose disruption enhances Aβ clearance. Promising candidates will be then validated in vivo using antisense oligonucleotides.
The host laboratory has established the xenotransplantation model, the TurboID system, and the CRISPR platform, while I bring extensive expertise in human tri-cultures. I therefore believe that this makes an unprecedented opportunity to move beyond the state of the art and address a major gap in AD research.
The project will generate the first in vivo map of the human microglial lysosomal proteome under Aβ pathology, uncovering candidate therapeutic targets to restore clearance. In doing so, it will open new avenues to modify AD and other neurodegenerative disorders where protein accumulation and microglia dysfunction are key drivers.
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-2025-PF
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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.