4 Year MRC PhD Programme: Signalling pathways regulating intraepithelial lymphocytes in the gut

Intraepithelial lymphocytes (IEL) are the first immune cells that pathogens encounter in the gut. These T lymphocytes lie within the epithelial layer, and are central to controlling infection, stress or transformation of the gut epithelium. At the same time, deregulation of IEL responses can lead to inflammatory bowel diseases such as colitis and Crohn’s disease. Despite their importance, we have a poor understanding of how IEL sense and respond to stress and infection of the intestinal epithelia, and how they maintain their quiescence in the presence of the normal gut microflora. The aim of this project is to address the signalling pathways that regulate IEL function using state-of-the-art proteomics methods to quantify post-translational modifications and their dynamic changes during oral pathogenic infection. These approaches will be integrated with flow cytometry and basic biochemistry to map the signalling networks utilised by these specialised lymphocytes. The student will address the relevance of identified signalling pathways for IEL function in vivo by studying infection of mice with oral pathogens, germ-free mouse models, and genetically modified systems.

The student will work within the laboratories of Dr. Swamy and Dr. Kulathu, both within the MRC Protein Phosphorylation and Ubiquitylation unit, one of the world’s leading centres studying the roles of signal transduction in health and disease. The student will have the opportunity to learn in vivo and in vitro immunological techniques (Swamy lab), and biochemical and novel proteomics-based methodology (Kulathu lab).