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Identification and characterization of enteric nervous system stem cells

Project description

Cellular and molecular characterisation of the ‘second brain’

The enteric nervous system (ENS) is the intrinsic nervous system of the gut and lines the walls of the gastrointestinal tract. It interacts with the activity of the intestinal immune system, the epithelial barrier and microbiota to orchestrate intestinal homeostasis. The scope of the EU-funded IDENSTEM project is to characterise the cellular mechanisms underlying the function of the ENS. Researchers will focus on a specific population of enteric glial cells and investigate their role under a steady state and in response to injury. Moreover, they are interested to examine the contribution of these cells to intestinal inflammation, which is a hallmark of many intestinal diseases.

Objective

The digestive system is essential for water and nutrient uptake, waste removal and serves as a sensory system providing information to the central nervous system via the gut-brain communication axis. The gastrointestinal tract harbours the largest collection of neurons and glial cells collectively known as the enteric nervous system (ENS) and regulate digestive physiology independently of brain input. Intestinal function and homeostasis depend on the integrated and balanced activity of multiple gut tissues,in which, the ENS plays a critical role by actively interacting with the intestinal immune system, the epithelial barrier and microbiota. Developmental deficits or acquired disorders in any of these tissue components can result in debilitating gastrointestinal conditions, such as Hirschsprung disease (congenital megacolon) or inflammatory bowel disease. Despite critical contributions of the ENS to digestive physiology and intestinal homeostasis, very little is known about the cellular mechanisms that underpin its function at steady state conditions or in response to injury. IDENSTEM will address the identity and properties of ENS neural stem cells (ENSCs) using the mouse as an experimental model organism. Preliminary data suggest that a subpopulation of enteric glial cells expressing the Notch signalling target Hes5, undergo low rate proliferation and exhibit neurogenic potential. In this proposal, we aim to identify and characterize the cellular and molecular properties of this population. We wish to understand their contribution in maintaining ENS integrity under normal conditions or in response to injury/disease. These studies will advance fundamental neurogastroenterology and the development of novel therapeutic strategies for various gut disorders. Furthermore, they will provide insight into ENS contributions to the gut tissue circuitry and in intestinal inflammation. IDENSTEM will open a new window of knowledge to improve human health.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-ST - Standard EF

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

THE FRANCIS CRICK INSTITUTE LIMITED
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.

€ 212 933,76
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Region
London Inner London — West Camden and City of London
Activity type
Research Organisations
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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.

€ 212 933,76
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