Project: Understanding the role of MAIT cells in diverse parasitic infections
Eckle Group
Mucosal-Associated Invariant T (MAIT) cells are a subset of innate-like T cells which make up on average 3% of T cells in human blood, with larger fractions found in the tissues. It is well established that MAIT cells contribute to protection from bacterial and fungal infections [1]. This involves MAIT cells recognising a modified precursor of vitamin B2-biosynthesis found in many bacteria and fungi [2]. We recently found that MAIT cells contribute to protection from liver stage malaria and recognise a novel vitamin B2-biosynthesis independent antigen [unpublished]. We now seek to establish if and how MAIT cells contribute to protection from other parasitic infections.
Objectives and approaches:
Hypothesis: MAIT cells contribute to protection from a diverse range of parasitic infections
Aim (i): Investigate if MAIT cells contribute to reducing parasite burden in mouse models.
Aim (ii): Investigate if MAIT cells in human healthy donor blood respond to parasites, using an established in vitro assay and flow cytometry.
Aim (iii): Characterise the MAIT cell-mediated immune response to parasites, including the dependency of MR1-antigen, in humans and mice using flow cytometry and scRNAseq.
References
[1] Provine NM, Klenerman P. MAIT Cells in Health and Disease. Annu Rev Immunol. 2020.
[2] Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature. 2014;509:361-5.
Contact project supervisor for further
information and application enquiries
Eckle Group
2 vacancies
The Eckle group is interested in understanding the role of MAIT cells in diverse infectious diseases. 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. In collaboration with Dr Catarina Almeida we are also interested in understanding the molecular mechanisms of T cell mediated hypersensitivities involving both conventional and unconventional T cells (MAIT cells and CD1 restricted T cells). We study unconventional T cell responses using flow cytometry and RNA sequencing in mouse models, human blood and tissues and human reporter cell lines, and use a range of biochemical techniques for antigen discovery.
Eckle Group Current Projects
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Understanding the role of conventional and unconventional T cells (MAIT cells and CD1-restricted T cells) in allergies
PhD/MPhil, Master of Biomedical Science, Honours
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Understanding the role of MAIT cells in diverse parasitic infections
PhD/MPhil, Master of Biomedical Science, Honours
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Determining the role of MAIT cells in blood stage malaria
PhD/MPhil, Master of Biomedical Science, Honours
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Establishing a human liver-like assay for MAIT cell responses to liver stage malaria
PhD/MPhil, Master of Biomedical Science, Honours