Project description
Enterochromaffin cells and serotonin secretion
The impairments in communication between the gastrointestinal tract, the enteric nervous system (ENS) and the brain have been implicated in the pathogenesis of multiple disorders, including obesity, diabetes, visceral pain and inflammatory bowel disease. The enteroendocrine cells, particularly enterochromaffin (EC) cells, functioning as mechano- and chemoreceptors in serotonin secretion, are central to this communication and display molecular and morphological features that are reminiscent of neuronal synapses in the brain. The EU-funded SynGut project employs a multidisciplinary approach to unravel the molecular mechanisms mediating hormone secretion from EC cells and understand its functional consequences; moreover, it will shed light on the information transfer process to the ENS and the brain.
Objective
Communication between the gastro-intestinal (GI) tract, the enteric nervous system (ENS), and the brain plays an important role in regulating our behaviour, and accordingly, impairments in this communication have been implicated in the pathogenesis of multiple disorders including obesity, diabetes, visceral pain, and inflammatory bowel diseases. A better understanding of the molecular and cellular mechanisms of gut-to-brain signalling will be critical for treating these disorders. An important group of cells in this context are enteroendocrine cells (EECs), and most notably enterochromaffin (EC) cells, which function as mechano- and chemoreceptors and signal by secreting serotonin, however the release process is poorly understood. Strikingly, these cells show molecular and morphological features that are highly reminiscent of neuronal synapses in the brain, raising the intriguing hypothesis that they may form synapse-like contacts that lie at the heart of their communication mechanism. To date, however, this hypothesis has been difficult to test due to the low spatial density of EC cells along the GI tract. Using a multidisciplinary approach combining intestinal 3D-organoid cultures, correlative light- and electron microscopy, electrophysiology, and single-cell RNA sequencing, this project aims to address the questions i) which molecular mechanisms mediate hormone secretion from EC cells, ii) what are the functional properties of the release process, and iii) how are local circuits organized to signal information to the ENS and brain. The results from this study will allow me to answer the fundamental question whether EC cells form functional synaptic connections, as well as providing a comprehensive overview over the functional and molecular properties of these ‘synapses’.
Fields of science (EuroSciVoc)
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.
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.
- medical and health sciences clinical medicine gastroenterology inflammatory bowel disease
- natural sciences physical sciences optics microscopy electron microscopy
- medical and health sciences clinical medicine endocrinology diabetes
- natural sciences biological sciences genetics RNA transcriptomes
- medical and health sciences health sciences nutrition obesity
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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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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
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.
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.
MSCA-IF-EF-ST - Standard EF
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
1165 KOBENHAVN
Denmark
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.