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Immune mechanisms in Environment-induced brain plasticity: Role of T cell-ILC Crosstalk

Project description

The role of environmental enrichment in brain plasticity

Stimulating surroundings that provide enhanced sensory, cognitive and social experiences such as physical activity and social interaction are referred to as environmental enrichment (EE). EE promotes brain health and boosts neuroplasticity, stimulates new neuron formation and reduces neuroinflammation. Interestingly, it also alters immune responses in the brain, increasing T cell numbers and changing microglial activity. With the support of the Marie Skłodowska-Curie Actions programme, the NeuroTIC project aims to investigate how EE drives communication between immune cells and microglia to support brain adaptation. Using advanced molecular and genetic tools, researchers aim to identify key mediators of this neuroimmune cross-talk. They will also explore gene therapies that reproduce the beneficial effects of EE in neurodevelopmental disorders such as autism.

Objective

Neuroplasticity is the essential ability of the brain to respond and adapt to extrinsic and intrinsic stimuli, and it is strongly influenced by the environment we live in. Exposure to e nvironmental enrichment (EE) leads to neurological changes paralleled by changes in the immune system. EE promotes neurogenesis, neuroplasticity, and ameliorates neuroinflammation in both rodents and humans. Microglia and brain T cells also adapt their phenotype and T cell number increases, suggesting a connection between neural activity and immune response. How brain T cells or other lymphoid cells and microglia are able to respond to EE and eventually modify the brain is unknown.

I hypothesize that EE instigates a neuroimmune crosstalk between lymphoid cells and microglia to support the neuronal changes. To test this, I will use high-dimensional spectral flow cytometry and CITE-seq to map the changes in the intercellular communication networks induced by exposure of mice to EE and identify key cellular and molecular mediators. Next, I will combine depletion tools and genetic models to assess the specific role of different subsets of lymphocites in EE-induced brain plasticity. The final ambition of this project is to identify key molecular targets mediating EE-induced lymphocites-microglia crosstalk. I will then use a gene therapy approach to deliver candidate biologics to the brain. Using a mouse model of Autism, I will provide impactful proof-of-concepts for the ability of immune molecular mediators to stimulate pathways of brain plasticity and mimic the benefits of environmental enrichment in neuropathology.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

VIB VZW
Net EU contribution

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€ 200 400,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
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Research Organisations
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