Project description
Programming brain immune cells to repair Alzheimer’s disease
The brain harbours specialised immune cells that maintain neural health and respond to disease. In Alzheimer's disease, this immune balance is disrupted, with inflammatory cells infiltrating the brain and accelerating damage. There are two resident immune populations, microglia and border-associated macrophages, that play complementary yet distinct protective roles. However, it remains unknown what determines whether incoming immune precursors develop into one type or the other. With the support of the Marie Skłodowska-Curie Actions programme, the myeloFateTune project aims to identify the key molecular players of human brain immune cell development. The goal is to programme human monocytes to adopt beneficial brain immune identities before reinfusion, thereby establishing a realistic cell-based therapeutic strategy for Alzheimer’s disease.
Objective
Alzheimer’s disease upends the brain’s immune balance by admitting peripheral myeloid cells that intensify inflammation and damage. Two resident guardians from identical ontogeny, microglia in the parenchyma and border-associated macrophages at the brain’s interfaces, are non-redundant and normally sustain synapses and neurovascular health. Yet we still lack a human map of the receptor cues that decide whether incoming precursors settle as microglia or as border macrophages, and how that allocation shapes disease.
This fellowship will close that gap. I will use a human microglia xenotransplantation model in which PSC-derived primitive myeloid precursors engraft into neonatal mouse brains, then apply a focused pooled CRISPR screen with high-parameter fate readouts to build the first receptor-to-fate atlas inside a living mammalian brain. Top receptor 'levers' will be rebuilt in arrayed lines and tested head to head by mosaic co-engraftment to obtain within-brain effect sizes. Fate will be coupled to function at Alzheimer-relevant endpoints such as plaque compaction, antigen presentation, lipid and oxidative tone, synaptic integrity, and vascular reactivity. Finally, I will translate these levers by programming primary human monocytes ex vivo to bias them toward microglia-like or border-like identities, followed by reinfusion, providing a realistic route for cell-based therapy. Together these steps convert descriptive atlases into manipulable circuitry and establish causal, human-specific checkpoints that steer myeloid allocation in vivo.
By showing that allocation can be tuned and that tuning improves repair-linked programs, this project will deliver a therapeutic concept and a deployable toolkit: validated levers, minimal spectral panels, an identity scoring codebase, and FAIR data and protocols for the community. It will also accelerate my transition to independence at the interface of neuroimmunology, functional genetics, and high-dimensional cytometry.
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.
This project's classification has been human-validated.
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.
This project's classification has been human-validated.
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-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.