4 Year Wellcome Trust PhD Programme : Keeping the peace: investigating the regulation of gut lymphocytes in homeostasis and disease

Our bodies are home to trillions of bacteria and most of them reside in our guts. There is increasing evidence of links between our intestinal microbiota and inflammatory diseases including cardiovascular complaints, obesity, cancer and more directly, inflammatory bowel diseases. A single layer of epithelial cells forms the first line of defence in the gut and is the largest interface between microbes and our bodies. This layer of cells is interspersed with specialized immune cells known as Intraepithelial lymphocytes (IEL) that aid in its protection. IEL are T cells that are central to controlling infection, stress or transformation of the gut epithelium. While we know a lot about conventional T cell signalling, we still have a poor understanding of signalling in unconventional T cell subsets like IEL, how IEL get activated in response to stress and infection of the intestinal epithelia, and how they maintain their quiescence in the presence of the normal gut microflora.
The research in my lab aims to define the nature of the signals that activate intestinal IEL, and how they are kept in check under normal resting conditions. Potential PhD projects include using novel mouse models to address the function of IEL in cancer and infection, and to dissect the signalling pathways that regulate IEL function. The student will address these questions using a combination of biochemistry, proteomics, new and established knockout mouse models, and in vivo infection studies.