Project: Understanding the life and death of MAIT cells.
We, and others have shown that mucosal-associated invariant T (MAIT) cells respond to infection by dramatically expanding in number (for example during a Legionella lung infection model in mice). After the infection is cleared, MAIT cells are retained at high numbers, which contradicts normal contraction of conventional T cells. Contraction of the conventional T cell population after the clearance of infection is necessary to prevent uncontrolled T cell responses and damage to the host.
The balance between life and death in a cell is finely controlled by intricate signalling pathways, including the well-defined death pathways regulating apoptosis and necroptosis. We have intriguing data to show that MAIT cells differ in these death pathways compared to other cells. This project seeks to understand these differences, and how they contribute to the longevity of MAIT cells. Results may have implications for understanding the role of MAIT cells throughout infection, and in targeting these cells for vaccination against infectious diseases.
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.