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Micro-environmental control of gut renewal

Supervisor: Golnar Kolahgar

The intestinal epithelium constantly regenerates from stem cells, which adjust their behaviour to the changing physiological conditions the gut is exposed to. For example, stem cell proliferation rates can transiently increase to speed up regeneration after tissue loss or in response to the diet, before reverting to steady-state levels once correct tissue size is reached. This plasticity is essential for intestinal function, as lack of regeneration causes tissue atrophy whereas unrestricted stem cell proliferation promotes cancer. We use the genetically tractable Drosophila gut to identify the secreted and physical factors regulating gut plasticity. In particular, we use targeted genetic screens and functional analyses, to identify novel extracellular signalling molecules regulating cell proliferation in contexts that trigger reversible changes in gut size. As the regulation of intestinal proliferation is largely conserved between Drosophila and mammals this work has the potential to uncover important new principles relevant to intestinal maintenance and degenerative diseases.

Rotation students can choose between one of the following projects:

1. Investigation of the crosstalk between the intestinal epithelium and the visceral mesoderm.

2. Identification by RNAi screening of new factors contributing to gut renewal in varied dietary conditions.

The student will learn about Drosophila genetics, immunohistochemistry, confocal microscopy, and will have the option of expanding on the project for their PhD.

 

Relevant references

Kolahgar G, Suijkerbuijk SJE, Kucinski I, Poirier E, Mansour S, Simons BD, Piddini E. Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Dev Cell. 2015 Aug 10, 34(3):297-309 

Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E. Cell competition drives the growth of intestinal adenomas in Drosophila. Curr Biol. 2016 Feb 22;26(4):428-38.