Project description
Origins of monocyte-derived macrophages
Macrophages are cells of the immune system that not only defend against disease but also play a key role in tissue maintenance. They originate early in embryonic life but are later replenished by circulating monocytes which differentiate into macrophages during inflammation or tissue repair. Understanding how these monocytes turn into macrophages is key to targeting them in diseases such as cancer, cardiovascular and autoimmune disorders. The ERC-funded MONOSPLIT project aims to investigate the two distinct developmental pathways of monocytes and their impact on macrophage diversity. In this context, researchers will use advanced single-cell imaging, genetic tools and molecular profiling. Project findings could pave the way for new diagnostic and therapeutic strategies that modulate macrophage activity in health and disease.
Objective
Macrophages are key players in organ development, tissue maintenance, and the immune defense of vertebrate organisms. These cells are initially established during embryonic development, but most tissue-resident macrophage compartments are progressively seeded and often even replaced by monocyte-derived cells. Monocytes and their macrophage progeny critically contribute to a wide range of pathologies, including autoinflammatory, cardiovascular, and metabolic disorders, as well as cancer. Given their central role in physiology and pathophysiology, these cells are attractive targets for therapeutic intervention. This will, however, require an in-depth understanding of monocyte-to-macrophage trajectories, whose comprehensive study in mice and man is the goal of this proposal.
Beyond these translational implications, our studies are particularly well-timed, given new exciting findings: thus, monocytes were recently shown to arise from distinct developmental trajectories, and we discovered that this developmental monocyte dichotomy translates into tissue macrophage heterogeneity with probable significant functional impact.
Here, we propose to follow up on our recent intriguing finding and use murine fate mapping and novel Csf1r-targeted genetic perturbations, combined with a high-resolution single-cell-based imaging and omics analysis of murine and human blood, to explore the impact of developmental monocyte dichotomy on health and disease in man and mice.
An in-depth understanding of the two monocyte trajectories, their differential dominance following infections, and differential fates in distinct tissues will have significant value for the future development of strategies for tissue macrophage manipulation. Moreover, our detailed analysis of human blood might incentivize routine monitoring of the monocyte-to-macrophage axis for diagnosis.
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.1.1 - 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-2024-ADG
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7610001 Rehovot
Israel
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