What keeps the gut stem cell niche healthy? (SOBOLEWSKI_U18DTP)
- Research Area Bioscience for Health
- Partner The University of East Anglia (UEA)
Dr Anastasia Sobolewski -
- Application Deadline 27/11/2017
A normal functioning epithelium is vital for a healthy gut. The epithelium forms a protective barrier between the bacteria and food contents in the intestine and the underlying immune system, so preventing an immune response. Renewal takes place through 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.
We have shown that the epithelial layer ‘auto regulates’ (autocrine signalling) its growth through interleukin 6 signalling at the stem cell niche (Jeffery et al. 2017), and that immune cells (monocytes/macrophages) can modulate epithelial stem cells and regulate epithelial renewal (Skoczek et al. 2014) i.e. paracrine.
This project will determine the role of IL-6 autocrine and paracrine signalling in stem cell driven renewal of the colonic epithelium. Colon homeostasis is pertinent to study as it is the major site for the development of ulcerative colitis and colon cancer. The objectives of this PhD are to; i) Characterise the effects of IL-6 on epithelial stem cells and epithelial renewal ii) Determine the role of IL-6 autocrine signalling in the epithelium iii) Investigate the role of the IL-6 signalling pathway in immune cell regulation of the epithelium.
The student will be trained in primary gut stem cell / ‘mini gut’ colonoid culture and co-culture with macrophages. They will gain expertise in confocal and time-lapse microscopy, flow cytometry, PCR, FACS and image software analysis. The student will present their work at research seminars, International Conferences, attend a bioimaging workshop and join the East Anglian British Society of Immunology Group.