Inflammatory bowel disease (IBD) is common and debilitating condition which disproportionally affects the Irish population. IBD patients have a leaky gut due to weakened intestinal epithelial barrier which leads to gut bacteria entering the mucosa and causing inflammation in the intestinal wall. While there have been some recent improvements in therapeutic options for IBD patients, all of these target the inflammation occurring in the gut rather than the leaky epithelium itself and therefore have significant limitations. There is therefore a large unmet clinical need for new therapeutics in IBD. The Taylor lab has recently shown that targeting oxygen sensitive pathways may represent a new therapeutic approach to IBD by targeting the leaky barrier raising the prospect of a new and improved therapy. I hypothesise that the tissue oxygen level is an important determinant of the intestinal barrier. In this patient sample-based study, I will use intestinal biopsies that have been collected from IBD patients where intestinal oxygen levels have been measured to characterise the effects of low oxygen hypoxia on the intestinal epithelial barrier. I will use a state-of-the-art imaging approach matched with standard molecular biological techniques to characterise the relationship between tissue hypoxia and barrier function in IBD patients. The successful completion of this work will allow me to gain extensive experience in world class translational medical research and may uncover a new therapeutic target for the treatment of IBD.
