University of Dundee

Interrogating the functions of intestinal intraepithelial lymphocytes

Within the epithelial layers of our barrier surfaces resides a complex and unconventional pool of T cells collectively called intraepithelial lymphocytes (IEL). At the intestine, IEL patrol the single layer of epithelium that lies between the external environment exposed to chemicals, food, and pathogens, and the sterile internal environment. Due to their strategic placement, intestinal IEL are the first immune cells that come in contact with potentially harmful agents, and are tasked with eliminating infected or damaged epithelial cells, and maintaining mucosal homoeostasis. On the other hand, dysregulation 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 research in our lab aims to define the nature of the signals that direct IEL function in infection control, anti-tumour immunity, and metabolism. We are also investigating how IEL communicate with epithelial cells using state-of-the-art proteomics, phosphoproteomics and biochemistry.

Potential PhD projects include using novel mouse models to address the function of IEL in cancer and infection, dissecting the molecular mechanisms that IEL use to kill infected/stressed intestinal epithelial cells, and/or defining the signalling pathways that are activated in IEL in response to intestinal stress. The student will address these questions using a combination of biochemistry, proteomics, multi-colour flow cytometry, new and established knockout mouse models, and in vivo infection or carcinogenesis studies.

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