Projektbeschreibung
Enterochromaffine Zellen und Serotonin-Sekretion
Eine gestörte Kommunikation zwischen dem Magen-Darm-Trakt, dem enterischen Nervensystem und dem Gehirn trägt zur Pathogenese verschiedener Erkrankungen und Beschwerden bei, wie Adipositas, Diabetes, viszerale Schmerzen und entzündliche Darmerkrankungen. Enteroendokrine Zellen, vor allem enterochromaffine Zellen, die bei der Serotonin-Sekretion als Mechano- und Chemorezeptor agieren, sind für diese Kommunikation von zentraler Bedeutung. Außerdem besitzen sie molekulare und morphologische Funktionen, die an neuronale Synapsen im Gehirn erinnern. Mithilfe eines multidisziplinären Ansatzes möchte das EU-finanzierte Projekt SynGut die molekularen Mechanismen aufklären, welche die Hormonsekretion aus den enterochromaffinen Zellen vermitteln, und die entsprechenden funktionellen Konsequenzen ermitteln. Darüber hinaus wird es Aufschluss über den Informationsaustausch zum enterischen Nervensystem und Gehirn geben.
Ziel
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’.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- natural sciencesphysical sciencesopticsmicroscopyelectron microscopy
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health scienceshealth sciencesnutritionobesity
Programm/Programme
Thema/Themen
Aufforderung zur Vorschlagseinreichung
Andere Projekte für diesen Aufruf anzeigenFinanzierungsplan
MSCA-IF-EF-ST - Standard EFKoordinator
1165 Kobenhavn
Dänemark