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 PhD 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.
This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/study/postgraduate/research-degrees/fees-and-funding
A bench fee is also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.
For more information on the supervisor for this project, please go here: https://www.uea.ac.uk/biological-sciences/people/profile/a-sobolewski
Type of programme: PhD
Project start date: October 2019
Mode of study: Full time
Entry requirements: Acceptable first degree - Biological Sciences.
The standard minimum entry requirement is 2:1.
Deadline for applications: 31 May 2019