Project description
Building neuronal diversity in the gut
The enteric nervous system (ENS) is a vast network of neurons embedded in the gut wall that independently regulates gut function. The diversity of enteric neurons is central to gut health. Selective neuronal loss or dysfunction leads to common gastrointestinal disorders for which treatments remain limited. With the support of the Marie Skłodowska-Curie Actions programme, the DeSTENy project builds on the discovery that enteric neurons diversify through a stepwise developmental programme. The aim is to understand how time and location within the developing gut shape neuronal identity. By combining single-cell transcriptomics with gene manipulation, researchers will identify key drivers of ENS development across different gut regions. Project results are expected to advance regenerative strategies for the treatment of neurological gastrointestinal diseases.
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.
Fields of science (EuroSciVoc)
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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.
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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)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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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.
171 77 STOCKHOLM
Sweden
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