Project: Understanding the genesis of MAIT cell antigens
Our team identified the known natural mucosal-associated invariant T (MAIT) cell antigens, small molecule antigens which form as chemical adducts, incorporating microbial riboflavin biosynthesis metabolites and small cellular metabolites (e.g., methylglyoxal and glyoxal). Most work to date has focussed on the riboflavin-based metabolites made by microbes. We now seek to understand the impact of alterations in the concentrations of these small cellular metabolites on antigen formation and MAIT cell activation. Since tissue specific disease conditions are known to change the levels of methylglyoxal and glyoxal, this project may have implications for the role of MAIT cells in infection, inflammatory diseases, and cancer.
The Corbett group is part of the MAIT cell programme headed by Prof. Jim McCluskey, which also includes the group of Dr Sidonia Eckle and Dr Zhenjun Chen.
Mucosal-associated invariant T cells (MAIT cells) are a recently described set of unconventional T cells restricted by the MHC-I related protein 1 (MR1). MAIT cells are found in most mammals, including humans and mice, and are the most conserved set of T cells across different species. The protective and/or pathological role of MAIT cells in infections and other conditions, such as cancer, is still emerging. In light of their high frequency in humans, their functional potency and MR1 being monomorphic, MAIT cells are considered to be promising therapeutic and vaccination targets.
We are international leaders in MAIT cell research, having made significant breakthrough discoveries in MAIT cell immunity. These include identifying the antigens recognised by MAIT cells (Kjer-Nielsen et al. Nature 2012, Corbett, Eckle, Birkinshaw, Liu et al. Nature 2014, 2 patents) and the associated development of tetramers to characterise MAIT cells (Patented) (Reantragoon, Corbett et al. JEM 2013) as well as the establishment of several mouse models of disease in order to understand the role MAIT cells play in protective and aberrant immunity (Chen et al. Mucosal Immunol 2017, Wang et al. Nature Comms 2018, Wang et al. Science Immunol 2020, Zhao et al. Nature Comms In Press).
We have weekly MAIT cell programme data meetings, and our groups collaborate closely on several projects. We also share lab and management resources as well as lab and office space. Students may also be interested in other projects in the MAIT cell programme (Chen group, Eckle group).
The Corbett group is interested in understanding the production of vitamin-based antigens which are recognised by MAIT cells, as well as the signals that drive MAIT cell functions in various infection and disease settings with the long-term goal of manipulating MAIT cells for clinical benefit (vaccination or immune therapy).
We currently have two student projects on offer. However, interested PhD candidates are welcome to contact us at any time to discuss additional projects.