Supervisors: Liam Morrison, Neil Mabbott

Project description:

We seek an enthusiastic student with experience in cell biology or immunology for an exciting four year Ph.D. studentship which aims to use bovine enteroid (‘mini-guts’) cultures as novel systems to analyse host-pathogen interactions in the intestine.  

In recent times there have been great advances in developing in vitro systems that much better represent the cellular and structural complexity of tissues in the living animal. A good example of this is the enteroid, which is a stem-cell derived and self-propagating ‘mini-gut’, whose 3-dimensional structure contains both a lumen and all of the cell types that make up the intestinal tissue1. Enteroids therefore are an ideal in vitro model for examining how pathogens interact with the lining of the intestine.  We have developed bovine enteroids2 and are applying them to study interactions with the protozoan intestinal pathogen of livestock and humans, Cryptosporidium parvum. However, the enteroids lack representation of cells of the immune system, which are clearly central to the host response to pathogens, but have also been shown to impact upon intestinal cell population homeostasis3. Immune cell complementation has not yet been developed for bovine enteroids, but would enable significantly enhanced analysis of both host-host and host-pathogen cellular interactions. A major aim of this project is to advance the development of these enteroid cultures.  This will include developing protocols for co-culture with immune cells such as macrophages and dendritic cells.  Similarly, the ability to induce the differentiation of important epithelial cell subsets such as M cells and tuft cells will also be explored.  Each of these cell type populations are predicted to be critical in both the enteric immune response to pathogens and the overall maintenance of intestinal cell homeostasis3. These cultures will then be used to determine the factors which impact on intestinal cell homeostasis and pathogen dynamics in the bovine intestine.

The successful student will receive extensive training in cutting edge cellular, molecular and immunological techniques, including enteroid generation and maintenance, flow cytometry, confocal microscopy and bioinformatics analysis of gene expression. 

For further information please contact Dr Liam Morrison or Prof Neil Mabbott.

References:

1.    Sato & Clevers, 2013. ‘Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications.’ Science, 340: 1190-1194.
2.    Hamilton et al, 2018. ‘Development of in vitro enteroids derived from bovine small intestinal crypts.’ Veterinary Research, 49: 54.
3.    Sehgal et al, 2018. ‘The role of CSF1R-dependent macrophages in control of the intestinal stem cell niche.’ Nature Communications, 9: 1272.

If you wish to apply for this project, please check this link and send your application to this email.