Descripción del proyecto
Células enterocromafines y secreción de serotonina
Las deficiencias en la comunicación entre el tubo digestivo, el sistema nervioso entérico (SNE) y el encéfalo se han relacionado con la patogenia de varios trastornos, incluidos la obesidad, la diabetes, el dolor visceral y la enfermedad inflamatoria intestinal. Las células enteroendocrinas, especialmente las células enterocromafines (EC), que funcionan como mecano- y quimiorreceptores en la secreción de la serotonina, son fundamentales para esta comunicación y muestran características moleculares y morfológicas que recuerdan a las sinapsis neuronales del encéfalo. El proyecto SynGut, financiado con fondos europeos, emplea un método multidisciplinar para desvelar los mecanismos moleculares que median la secreción de hormonas desde las células EC y comprender sus consecuencias funcionales. Además, arrojará luz sobre el proceso de transferencia de información al SNE y al encéfalo.
Objetivo
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’.
Ámbito científico
- natural sciencesbiological sciencesneurobiology
- medical and health sciencesclinical medicinegastroenterologyinflammatory bowel disease
- natural sciencesphysical sciencesopticsmicroscopyelectron microscopy
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health scienceshealth sciencesnutritionobesity
Programa(s)
Régimen de financiación
MSCA-IF-EF-ST - Standard EFCoordinador
1165 Kobenhavn
Dinamarca