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Commensal microbiota regulation of neuro-immune networks

Project description

Crosstalk between microbiota and the enteric nervous system

The gut microbiota affects human health through the release of various bioactive molecules. Emerging evidence indicates that commensal bacteria also influence the enteric nervous system, the division of the autonomous nervous system that controls gastrointestinal behaviour. The aim of the EU-funded CeleSte project is to delineate the mechanism of neuronal sensing of bacterial molecules and understand how it also regulates immune function. Researchers will employ a multidisciplinary approach to dissect this microbiota–neuroimmune system crosstalk and identify the key players. Project results will pave the way towards novel therapeutic strategies for neurological disorders that share a gastrointestinal comorbidity.

Objective

The enteric nervous system (ENS), neuronal and glial cells, development and function can be influenced by the microbiota. Germ-free mice have defective maturation of enteric glial and neuronal cells; colonization with microbiota rescues these defects. Production of neuroregulatory molecules by these neuronal cells involved microbial product sensing via MYD88. Importantly, glial-specific or neuron-specific deletion of Myd88 leads to decreased intestinal neuroregulators and consequent impaired innate lymphoid cell (ILC) activation. The identity of commensal microorganisms and the neuronal and glial cells sensing molecular pathways that could influence neuroregulators secretion affecting neuroimmune interactions are unknown. By using neuronal-specific mutants and their colonization with distinct microbiota, the present project aims to understand how glial- and neuron-derived regulators are influenced by particular commensal microorganisms and how this active neuronal sensing impacts of defined neuroimmune cell units, notably on the glial-ILC3 and neuron-ILC2 interactions. For this purpose, we will take advantage of a strong collaborative environment and cutting-edge techniques, including gnotobiotic animals, cre-lox technology, and neurosphere-derived organoids. Deciphering these new pathways of ENS-microbial crosstalk will improve our understanding of this equilibrium and will contribute to the development of new therapeutic strategies in mucosal diseases. This highly innovative and interdisciplinary project will allow me to expand my conceptual and technical knowledge of the host-microbiota dialogue, acquire new technical skills and reinforce my scientific network.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-WF-2018-2020

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Coordinator

FUNDACAO D. ANNA DE SOMMER CHAMPALIMAUD E DR. CARLOS MONTEZ CHAMPALIMAUD
Net EU contribution

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.

€ 147 815,04
Address
AVENIDA BRASILIA, CENTRO DE INVESTIGACAO DA FUNDACAO CHAMPALIMAUD
1400-038 LISBOA
Portugal

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Total cost

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.

€ 147 815,04
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