Objective
The central nervous system (CNS) is tightly connected to the immune system, with border regions such as the meninges and choroid plexus acting as key immunosurveillance hubs. Dysregulation of the immune cell landscape can drive neuropathology, including neuroinflammation and cancer. Growing evidence highlights monocyte-derived cells (MdCs) as critical players, yet their functions and mechanisms remain poorly understood. Identifying and studying MdCs has been difficult because they closely resemble tissue-resident phagocytes, including microglia. Emerging single-cell atlases offer resolution but remain largely descriptive, mapping diversity without explaining how MdC states arise, when they change, or what they do.
Our work shows that MdCs can be both tissue-damaging and protective in neuroinflammation. This functional dichotomy appears context-dependent, shaped by the local microenvironment, consistent with compartmentalized inflammation in progressive multiple sclerosis (MS). To move beyond correlation and determine how CNS niches dictate MdC function, I propose REMIND, an integrated three-step research plan that combines spatiotemporal transcriptomic profiling to define context-dependent molecular and metabolic MdC programs (Aim 1: Discovery) with flow cytometry to link trajectories to functions at the protein level and conditional gene targeting to establish causal mechanisms and disease impact (Aim 2: Mechanism). Aligning the findings with human disease will advance the development of biomarker and therapeutic strategies for progressive MS, a major unmet medical need (Aim 3: Translation).
Together, REMIND will reframe how MdCs are viewed—moving beyond static “good vs. bad” labels to a dynamic, context-dependent causal model of imprinting that can be redirected. By clarifying how CNS niches shape MdC fate and function, this provides the mechanistic basis for improved diagnosis, progression monitoring, and targeted interventions in patients with CNS disorders.
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Keywords
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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.1.1 - European Research Council (ERC)
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
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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-ERC - HORIZON ERC Grants
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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) ERC-2026-STG
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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.
8006 Zurich
Switzerland
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