Project description
Microglia in brain repair
Microglia are the resident immune cells of the central nervous system and play a critical role in maintaining brain homeostasis, responding to injury, and modulating neuroinflammation. Recent research has shown that microglia exist in distinct states that vary depending on environmental cues, injury, or disease conditions. Understanding microglia states is crucial for developing therapeutic strategies targeting neuroinflammation and neurodegenerative diseases. The ERC-funded MicroDissect project aims to investigate the kinetics and roles of microglial states using a mouse brain repair model. Key objectives include mapping microglial state changes over time and space and developing molecular tools to manipulate these states.
Objective
Microglia, the macrophages of the brain, are critical regulators of many neurobiological functions and implicated by human genetics in several central nervous system diseases. Recent studies have revealed that microglia can adopt distinct co-existing subtypes, termed 'states'. Microglial states appear especially in the context of damage, disease or repair and understanding these states may lead to the ability to precisely modulate neuroinflammation. However, due to a lack of datasets and tools, the dynamics and functions of these microglial states are unknown, representing a poorly explored frontier of neuroscience.
The core goal of this proposal is to understand the kinetics and biological roles of microglial states. Using focal brain repair in the mouse as a model system, I will address this knowledge gap with three synergistic objectives. First, how do microglial states change in space and time? To answer this, I will unravel the dynamics of microglial states by generating a spatiotemporal atlas of gene expression at the single-cell level, from injury to full repair. Second, how do specific microglial states emerge and what are their functions? I will address this question by focusing on one state that interacts with the peripheral immune system and appears to be triggered by a particular cytokine. Finally, I will build novel molecular tools to genetically access and specifically arrest any microglial state. This will enable me to investigate their impact on remyelination and uncover the biological mechanisms by which microglial states orchestrate brain repair.
Together, this work will comprehensively dissect the biology of microglial states in brain repair and provide the enabling technologies to do the same in other contexts, from development to disease. It will open up microglial states to experimentation, resulting in a step change in our understanding of this important brain cell type.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
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Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Topic(s)
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
D02 CX56 Dublin
Ireland