Understanding and Controlling Gut Peristaltic Movements
Internship title: Understanding and Controlling Gut Peristaltic Movements
Name: Matière Systèmes Complexes
Affiliation: CNRS / Université Paris Diderot
Address: 10 rue Alice Domon et Léonie Duquet 75013 Paris
Name: Laurent Limat
Phone number: 0157277000
Name: Nicolas Chevalier
Phone number: 0157276259
Subject Keywords: Peristalsis, gut, enteric nervous system, embryonic development, biophysics
Tools and methodologies: Microdissection, organ culture, contractility measurement, oxymetry, confocal microscopy, calcium imaging, immunohistochemistry, gut motility analysis. New techniques always in development.
Summary of lab’s interests: The food bolus is transported in the gastrointestinal tract by wave-like contractions of smooth muscle within the wall of the intestine, a reflex movement called peristalsis. Its dynamics are complex and result from the combined action of muscle cells, neurons of the enteric nervous system [1–3] (the “second brain”), and Cajal cells. Our team aims at :
• Understanding peristaltic transport in the gut by studying its development in the embryo. The digestive reflex does not appear at once: it gradually matures and gains complexity as the embryo develops [4,5]. Studying the dynamics of the gut as successive cell layers differentiate in the embryonic intestine gives a unique opportunity to “reverse engineer” the gut peristaltic engine.
• Developing non-invasive biomedical methods to stimulate peristalsis in animals and ultimately human patients. Developing non-invasive biomedical methods to stimulate peristalsis in animals and ultimately human patients, for the treatment of widespread gastrointestinal pathologies such as Irritable Bowel Syndrome (IBS, 10-15% of population in Western Countries) or Gastroesophageal Reflux Disease (GERD, 10-20% of population in Western Countries).
Project summary: Depending on trainee motivation, he will be involved in either or both of these research directions. Research is carried out on chickens and mice. Techniques used and under development in the lab include microdissection, organ culture, contractility measurement, oxymetry, confocal microscopy, calcium imaging, immunohistochemistry, and gut motility analysis.
1. Chevalier, N. R. et al. How tissue mechanical properties affect enteric neural crest cell migration. Sci. Rep. 6, 20927 (2016).
2. Jacques, C., Dacher, N. & Chevalier, N. Myogenic to Neurogenic Control of Gut Motility in the Chicken Embryo. To be submitted to Front. Neurosci.
3. Khalipina, D. et al. Morphogenesis and biomechanical properties of the enteric nervous mesh network. To be submitted to BMC Biol. (2019)
4. Chevalier, N. R., Fleury, V., Dufour, S., Proux-Gillardeaux, V. & Asnacios, A. Emergence and development of gut motility in the chicken embryo. PLoS One 12, e0172511 (2017).
5. Chevalier, N. R. The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves. Philos. Trans. R. Soc. Biol. Sci. (2018), 10.1098/rstb/373/1758
6. Chevalier, N. R. et al. Mechanical Tension Drives Elongational Growth of the Embryonic Gut. Sci. Rep. 8, 1–10 (2018).
7. Khalipina, D., Dacher, N. & Chevalier, N. Smooth muscle contractility causes anisotropic growth of the embryonic gut. To be submitted to Nature
Interdisciplinary aspect of the project: The internship is at the crossroad of physics (electricity, membrane potential), developmental biology and medicine. Ongoing Collaborations: Institut de Recherche Biomédicale Henri Mondor (IMRB) , Imagoseine Imaging Platform, The Enteric Nervous System in Gut & Brain Disorders (TENS), Institut de Biologie Paris-Seine, Institut Jacques Monod, Harvard University.