Repairing the epithelial barrier in IBD to restore intestinal homeostasis
Supervisors
Prof Simon Milling, School of Infection and Immunity, University of Glasgow
Dr Miguel Pineda, School of Molecular Biosciences, University of Glasgow
Prof Konstantinos Gerasimidis, School of Medicine, Dentistry & Nursing, University of Glasgow
Prof Umer Ijaz, James Watt School of Engineering, University of Glasgow
Summary
Crohn’s disease (CD) is a common form of inflammatory bowel disease. It occurs when the immune system mistakenly attacks normal gut bacteria, damaging the intestine. People with CD are treated with immunosuppressive drugs. These are not always effective, and can lose efficacy over time. Dietary therapies are also highly effective in CD, altering the gut bacteria, and reducing inflammation. With our collborators we have performed clinical studies exploring dietary therapies, and examined immune mechanisms underlying treatment effects. Unfortunately, no current treatments restore health; people who stop therapy experience recurrence of inflammation, or ‘flare’. Here we will investigate the residual immunological mechanisms that persist in people receiving seemingly-effective treatements, focusing on the epithelial cells that form the gut barrier, using samples from completed and currently-active clinical studies. We will analyse existing spectral-flow cytometry data from blood of >100 participants, and existing single cell sequencing data from participants who provided colon biopsies before and after treatment. These data will be integrated with clinical results, and analysed using approaches including machine learning. Importantly we will also use state-of-the-art gut on a chip models to understand the effects of treatment on epithelial cells in the lab, to identify key molecular mechanisms causing flare in CD
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