This project will build on our knowledge of how parasitic helminths manipulate the host immune response, in a collaboration between the groups of Dr Henry McSorley (University of Dundee) and Dr Hermelijn Smits (Leiden University Medical Centre, the Netherlands). The successful candidate for this 4 year PhD position will spend significant time in both Dundee and Leiden, to identify, characterise and translate their findings.
While the immune system plays a critical role in combating infection, inappropriate regulation of immunity has a pathogenic role in many diseases including autoimmunity, allergic disease and cancer. IL-33 is a member of the IL-1 family that is released by damaged endothelial and epithelial cells. IL-33 release acts as a “danger” signal to activate inflammation. It is involved in the response to both helminth and fungal infections and is also known to play a pathogenic role in allergic diseases such as asthma. IL-33 acts on a subset of immune cells, including type 2 innate lymphoid cells
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.
Autophagy is a conserved process that allows cells to break-down and recycle proteins, organelles and remove intracellular pathogens. Although the basic mechanisms are conserved, it is now apparent that in mammalian cells autophagy is subject to complex regulation and can be divided into several distinct forms depending on the target structure. One area in which autophagy regulation is less well understood is in immune cell function. In particular, deregulation of autophagy can have severe consequences for immunological pathologies and, for example, lead to chronic inflammation.