Séminaire externe: Andrew NEISH

Quand ?	Le 01/10/2018, de 11:00 à 12:00
Où ?	1 place de l'école
S'adresser à	François Leulier
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Next week we will have the pleasure to host Pr Andrew Neish from Emory University, Atlanta, US. Andy is an expert of epithelial biology, especially in the intestine in the context of Host-Microbes interactions and uses mouse and fly models. His talk is entitled: Regulation of Epithelial Homeostasis by the Microbiota You'll find below an abstract of his work and a list of some of his important papers.

Abstract:

The resident prokaryotic microbiota of the intestine can influence normal gut proliferation, development, growth and response to injury. We describe a common paradigm wherein contact of prokaryotic organisms stimulate the enzymatic generation of reactive oxygen species (ROS) in the host epithelia in organisms as disparate as flies and mice. These events occur via the action of highly conserved NADPH oxidase enzymes (dNox in Drosophila and Nox1 in mammals). Interestingly, a subset of bacterial taxa, predominately Lactobacilli, potently stimulates Nox dependent ROS generation in both systems, and activates redox responsive transcriptional circuits, including the Nrf2/Keap pathway. Germ-free mice and flies exhibit reduced epithelial proliferation and increased sensitivity to tissue damage. Consistently, epithelial-specific Nox1 and Nrf2 null mice, and dNox and CnC (Nrf2 ortholog in flies) mutant Drosophila demonstrate aberrant intestinal stem cell dynamics and responses to injury. Conversely, commensal bacteria such as the Lactobacilli and Akkermansia accelerate epithelial cell movement and mucosal restitution mice and flies, and correct proliferative defects observed in germ-free animals, in a Nox1 and Nrf2 dependent fashion. At the tissue level, bacterially induced ROS generation is strikingly excluded from discrete stem cell niches, resulting in a redox gradient across stem cell compartments in both mice and flies that is absent in germ-free animals. Ectopic generation of ROS in enterocytes outside the stem cell niche phenocopied the effects of the natural microbiota. These data suggest how discrete taxa of bacterial symbionts utilize spatially compartmentalized generation of ROS for controlling highly conserved signaling events that regulate intestinal development and homeostasis

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Séminaire externe: Andrew NEISH

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