Project description
Mapping microglial endolysosomal networks in ageing and disease
Microglia are the resident macrophages of the brain that are essential for maintaining homeostasis, neuronal debris removal, and circuit development. They play a critical role in ageing and neurodegenerative diseases, and human genetics has identified endolysosomal changes of microglia as a key determinant of disease risk. The ERC-funded MicrogliaLysosome project aims to use TurboID proximity labelling proteomics to study the interactome of proteins associated with Lamp1-positive structures within microglia and BA macrophages across brain regions and ages. The project will produce a detailed proteomic map of microglial endolysosomal networks, identify regional and age-specific changes, shed light on the pathogenesis of neuroimmune disorders, and reveal potential targets for future therapies for neurodegenerative diseases.
Objective
Microglia, the brain’s primary macrophages, play essential role in preserving neuronal homeostasis, clearing debris and shaping neural circuits throughout life. These functions are pivotal, particularly in context of aging and neurodegenerative diseases. Human genetic studies implicate microglia in age-related neurodegenerative diseases, with alterations in their endolysosomal network emerging as a critical determinant of disease risk. However, how microglial endolysosomal functions alter during aging and disease remain poorly defined, limiting our understanding of their contribution to disease pathology. This project employs cutting-edge in vivo TurboID proximity labelling proteomics tool to elucidate dynamic protein-protein interactions within Lamp1-associated cargoes in microglia and border-associated macrophages (BAMs). I will generate a high-resolution endolysosome-associated proteomic atlas of microglia and BAMs across distinct brain regions and ages. This atlas will identify proteomic changes and mechanisms that underpin neuroimmune dysfunction associated with aging and disease. By studying systemic and localized pathophysiological stressors, I aim to uncover compartment-specific disruptions in brain macrophages in vulnerable brain regions and their susceptibility to confer disease risk associated with aging and neurodegeneration. Using advanced spatial omics, computational tools, and functional in vivo and in vitro approaches in mice and human cells, I will define age- and region-specific microglia and BAM proteomic changes and map molecular microenvironments facilitating neuro-glia-immune crosstalk. This work addresses critical gaps in understanding microglial endolysosomal dysfunction and neuro-glia-immune crosstalk relevant to neurodegeneration. Resulting insights will revolutionize understanding of neuroimmune regulation and identify actionable immune molecular targets and biomarkers to inform the development of future therapeutic strategies.
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 neurobiology
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- medical and health sciences basic medicine pathology
- 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.1.1 - 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
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) ERC-2025-COG
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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.
WC1E 6BT London
United Kingdom
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