Project description
Choroid plexus epithelium as an indirect body-brain communicator
Nature protects the central nervous system (CNS) from harmful substances with specialised barriers between it and the blood, preventing bacteria and other large molecules from crossing. The blood-cerebrospinal fluid (CSF) barrier is established by epithelial cells of the choroid plexus that produces CSF. The single-cell-layer epithelium faces the blood on one side and the CSF on the other, putting it in a unique position to communicate between the periphery and the brain. The ERC-funded BrainGate project aims to investigate whether peripheral immune and microbial factors from the gut and traveling in the blood shape brain function indirectly via the choroid plexus epithelium and its effects on the CSF.
Objective
In contrast to other organs, the brain is surrounded by a system of specialized anatomical barriers isolating it from direct contact with immune cells and microbial products present in the blood. However, such factors do dynamically shape brain function in homeostasis and disease. Because of this unusual anatomy, the pathways of blood-brain communication are still poorly understood, while this understanding would provide a fundamental insight into brain function regulation, and enrich the current knowledge of neurological disease mechanisms. My previous work suggests that the choroid plexus (CP) is a central player mediating the influence of immune and microbial signals on the brain. The CP epithelium is a monolayer barrier tissue, which on the side facing the blood has the ability to sense such peripheral factors, and on the side facing the brain, produces the cerebrospinal fluid (CSF)a liquid carrying nutrients and signaling molecules, which contacts nearly all brain cells, and ensures brain homeostasis. I therefore hypothesize that peripheral immune and microbial factors may shape brain function indirectly, via regulation of the CSF properties at the CP epithelium.
Based on our preliminary data, and building on my past expertise in CP biology, neuroscience and immunogenomics, here I propose an interdisciplinary project BrainGate, striving to illuminate the physiological mechanisms and roles of gut-blood-CP-brain communication axis during post-natal development (Aim 1), under conditions of microbiota perturbation (Aim 2) and along the circadian cycles (Aim 3). By developing new tools for CP-specific genetic perturbation and combining them with approaches of spatial transcriptomics and behavioral readouts in mouse models, this project will reveal fundamental principles of physiological regulation of brain development, function and maintenance and pave the way for future investigation of the gut-blood-CP-brain communication circuit in neurological disease.
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
- medical and health sciences basic medicine anatomy and morphology
- 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)
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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)
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(opens in new window) ERC-2022-STG
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75724 Paris
France
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