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SpatioTemporal Diversification of Enteric Nervous system

Objective

The enteric nervous system (ENS) contains an extensive range of neural subtypes that collectively control essential gut functions largely independent of the central nervous system (CNS). Enteric neuronal diversity is critical for maintaining normal gut function, and a selective dysfunction or local neuronal loss leads to gastrointestinal (GI) disorders. As current treatments of ENS-related disorders are suboptimal, development of novel regenerative approaches has the potential to significantly improve GI health for millions worldwide. As a first milestone towards cell-based regenerative therapies, the Marklund lab recently established a molecular classification of intestinal enteric neurons and discovered that they diversify through a conceptually new stepwise principle during development. The proposed project, DeSTENy, will significantly expand on these discoveries, and investigate how time and spatial context of developing GI tract controls the developing ENS to acquire the appropriate neuron identities at the right time and region within the mouse gut. DeSTENy will integrate cutting-edge regular and spatial single-cell transcriptomics to identify potentially important spatiotemporal driver genes in the ENS of the intestine versus stomach and oesophagus (upper GI-tract). While studies of the developing ENS has been challenged by its inaccessible location within the gut wall, DeSTENy will overcome this limitation by the utilization a precise, rapid and large-scale gene manipulation strategy based on ultrasound-guided transduction of ENS precursor cells followed by temporally controlled gene expression. Apart from transforming our understanding of the largest division of the peripheral nervous system and fundamental developmental processes, DeSTENy will open avenues for regenerative medicine in treating neurological gut disorders, in particular the many affecting the upper GI-tract.

Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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-2023-PF-01

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Coordinator

KAROLINSKA INSTITUTET
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.

€ 222 727,68
Address
NOBELS VAG 5
171 77 STOCKHOLM
Sweden

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Region
Östra Sverige Stockholm Stockholms län
Activity type
Higher or Secondary Education Establishments
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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.

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