Investigation of the cell shedding process in small intestinal epithelium

The small intestinal epithelium of mammals constantly renews itself. Cells are produced by stem cells which are located at or near the base of small intestinal crypts. These cells migrate up the crypt-villus axis and differentiate during this process. Eventually cells are shed from the upper portion of the villus into the gut lumen. Disruption of this cell shedding process can potentially cause alterations in the gut barrier, leading to translocation of bacterial species into the organism and thus the development of various diseases, including inflammatory bowel diseases.

Over recent years our group at the University of Liverpool in collaboration with Prof Alastair Watson at the University of East Anglia has developed novel experimental techniques for evaluation of cell shedding in both mouse (1, 2) and human (3, 4) small intestine. In addition, we have shown that cell shedding is disrupted in human patients with Crohn’s disease (5). Recently we have also discovered substances which stimulate the cell shedding process in mouse small intestine. These techniques will in future permit us to investigate the mechanisms that are responsible for cell shedding in the mammalian small intestine.

This project will investigate in more detail the molecular and cellular mechanisms that are responsible for small intestinal cell shedding. Most experiments will involve mouse tissues, but some human studies are also possible. Techniques to be employed will include experimentation using various transgenic mouse strains, in vivo confocal microscopy, immunohistochemistry, Western blotting and real-time PCR.