Project description
Deciphering the genetic regulation of macrophage dysfunction in chronic inflammation
Macrophages are essential immune cells that play a key role in inflammation regulation and tissue homeostasis. Research has revealed that dysregulated macrophages significantly influence chronic inflammation, but the molecular mechanisms behind this behaviour are unclear. Supported by the Marie Skłodowska-Curie Actions programme, the MACROCODE project aims to work out the mechanisms that lead to the altered function of macrophages during chronic inflammation. To do so, it will perturb genes in macrophages that exhibit dysregulated expression in chronic inflammatory conditions and develop a computational framework to link these perturbed genes to transcriptomic programmes, cellular functions and disease phenotypes. Finally, it will validate key genes by modulating their expression to assess the impacts on macrophage differentiation, identity and function.
Objective
Macrophages are essential cells of the innate immune system, playing crucial roles in coordinating inflammatory responses and maintaining homeostasis. In cases of chronic inflammation, damaged tissues release abnormal signals that attract macrophages precursors to the local environment and drive macrophages toward a proinflammatory phenotype. This creates a feedback loop that sustains inflammation. The consequences to society are huge: chronic inflammatory diseases are among the leading causes of death and disability worldwide.
Recent single-cell multi-omics studies have identified dysregulated macrophages as central players in chronic inflammation, but the molecular mechanisms sustaining these responses remain poorly understood.
MACROCODE aims to unravel the molecular mechanisms governing the altered function of macrophages during chronic inflammation.
The specific aims of this project are:
1. Use CRISPR-Cas9 technology with single-cell read-outs to perturb genes in macrophages that show dysregulated expression between healthy and diseased states in chronic inflammatory conditions . Genes will be selected by creating an integrated single-cell transcriptomics atlas of macrophages in both health and disease.
2. Develop a computational framework using bioinformatics and AI tools to link these perturbed genes to transcriptomic programs, cellular functions and in vivo disease phenotypes.
3. Validate key genes by modulating their expression using dCas9-VPR or KRAB systems, and evaluate the effects on macrophage differentiation, identity and function.
Altogether, MACROCODE will decode the genetic regulation of macrophage dysfunction in chronic inflammation. This multidisciplinary project will equip me with advanced skills in genomics and bioinformatics, enhance my leadership and transferable skills, and prepare me for a future as an independent leader in the field of gene therapy for immune diseases.
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.
- natural sciences biological sciences genetics
- medical and health sciences basic medicine physiology homeostasis
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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-2024-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.
CB10 1SA SAFFRON WALDEN
United Kingdom
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.