Project: Probing the generality of MAIT cell antigen creation
We previously discovered the dominant microbial MAIT cell antigens, 5-OP-RU and 5-OE-RU, which are presented by MR1. 5-OP-RU and 5-OE-RU are adducts of an intermediate in riboflavin biosynthesis (5-A-RU) and small carbon compounds (methylglyoxal and glyoxal, respectively). Whether other small carbon compounds can form adducts with 5-A-RU that act as MR1 ligands is unknown. Using a combination of cellular and biochemical methods this project will screen a library of small carbon compounds for their ability to form adducts with 5-A-RU, binding to MR1 and stimulating MAIT cells.
This project will probe the generality of 5-A-RU based MR1 ligand creation with small carbon compounds. It also has the potential to identify novel MAIT cell antigens which might be produced during certain infections or perturbed metabolism. As such findings from this project may have implications for MAIT cell immunity in these settings.
The Eckle group is part of the MAIT cell programme headed by Prof. Jim McCluskey, which also includes the group of A/Prof. Alexandra Corbett 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 (see Corbett Group and Chen Group)
The Eckle group is interested in understanding the role of MAIT cells in diverse infectious diseases as well as in aberrant immunity, such as in allergies. We are also interested in understanding the mechanisms that drive MAIT cell function with a particular focus on the discovery of antigens and their recognition by MAIT cell receptors. Our long-term vision is to harness MAIT cells for immunotherapies and vaccines.
We currently have four student projects on offer. However, students interested in PhD/MPhil are welcome to contact us at any time to discuss additional projects.
Eckle Group Current Projects
PhD/MPhil, Master of Biomedical Science
PhD/MPhil, Master of Biomedical Science, Honours
Understanding the role of, and manipulating MAIT cells in protection from, diverse microbial infections