China Scholarship Council: Investigating the role of intestinal T cells in the response to diet

Intraepithelial T lymphocytes (IEL) are at the forefront of mucosal immunity – the first immune cells that pathogens encounter in the gut. IEL are central to the protection of the gut against infection and dietary stress, but dysregulated IEL responses are also associated with autoimmune inflammatory bowel diseases such as Coeliac and Crohn’s disease. These unique T cells reside between nutrient-absorptive intestinal epithelial cells that dictate the fuels available to IEL to allow them to function, but how IEL regulate nutrient absorption and are regulated by the diet is unknown.  

The aim of this project is to investigate how metabolic adaptation of IEL to the intestinal environment, allows IEL to respond appropriately to intestinal metabolic perturbations, including diet and microbial challenges. We will explore how cellular bioenergetics, macromolecule biosynthesis, and metabolite waste management are regulated in IEL, and how nutrient availability may regulate IEL cross talk with the epithelium. In this project, the student will learn to use state-of-the-art techniques to study metabolism, including metabolomics, mass spectrometry, high-resolution imaging, signalling studies to investigate the pathways regulating IEL metabolic adaptations, and in vivo models with different diets to address how perturbations in these pathways regulate intestinal homeostasis. 

These studies will provide fundamental insights into how the unique gut-resident immune cells adapt to their environment to maintain the balance between diet, the epithelium and immune responses, findings that can be used to tune IEL activity for treatment of infectious, autoimmune and/or metabolic diseases. 

Our research community thrives on the diversity of students and staff which helps to make the University of Dundee a UK university of choice for postgraduate research. We welcome applications from all talented individuals and are committed to widening access to those who have the ability and potential to benefit from higher education. 

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