Feeding gut stem cells to keep them healthy (SOBOLEWSKIAU20SCIEC)

A normal functioning epithelium is vital for a healthy gut. The epithelium forms a protective barrier between bacteria in the intestine & the underlying immune system, so preventing an immune response. Renewal takes place by division of epithelial stem cells, which change into other epithelial cell types (e.g. absorptive enterocytes) that are necessary for the gut to function normally. There is a lack of knowledge as to what regulates renewal at the epithelial stem cell niche during health versus inflammation.

We have shown that the epithelial layer auto regulates its growth through specific stem cell niche signalling pathways (Jeffery et al. 2017), that immune cells can modulate epithelial stem cells & epithelial renewal (Skoczek et al. 2014) & that the nutritional compound Quercetin, can modulate gut immune responses (De Santis et al. 2017). Understanding which nutritional products can promote healthy epithelial renewal is important for the development of new functional foods. This PhD project aims to understand how Quercetin exerts its effects and will utilise novel drugs to try & uncover the cell key signalling pathways that keep the gut healthy.
PhD objectives are to:

i) Characterise the effects of Quercetin on epithelial stem cells & renewal
ii) Define the key epithelial signalling pathways involved in renewal using novel drugs
iii) Determine the effect of Quercetin on the crypt epithelium during inflammation

The student will be trained in primary gut stem cell/‘mini gut’ colonoid culture & co-culture with macrophages. They will gain expertise in confocal & time-lapse microscopy, flow cytometry, PCR, FACS & image software analysis. The student will present their work at seminars, international conferences, attend a bioimaging workshop & join the East Anglia British Society of Immunology Group.

For more information on the project’s supervisor, please visit: https://people.uea.ac.uk/a_sobolewski
Start date of project: October 2020
Mode of study: full time
Studentship length: funded for 3 years
Location: UEA
Entry requirement: acceptable first degree in Biological Sciences. The standard minimum entry requirement is 2:1.