Project: MR1 – a molecular detection system for bacteria
Villadangos Group
MR1 functions as a molecular ‘alarm system’ to detect a diverse range of microbes – to alert the immune system of infectious bacteria or to monitor our microbiome. It does this by capturing metabolite by-products from bacteria and presenting them at the cell surface to activate a highly abundant T cell subset, called mucosal-associated invariant T (MAIT) cells. MR1 is a highly conserved piece of the mammalian immune repertoire, yet basic aspects of it are not well understood. Several projects are offered that will examine these important questions to reveal how MR1 contributes to human health: (i) to investigate the molecular machinery underpinning MR1’s function and expression, using CRISPR/Cas9 gene editing and cutting-edge cell biology techniques; (ii) to investigate how cells capture and traffic microbial metabolites for loading onto MR1 molecules, using chemical biology and proteomics; and (iii) to uncover how antigen presenting cells mediate the maintenance of the microbiome by MAIT cells, using proteomics and single-cell transcriptomics.
Supervisors:
Dr Hamish McWilliam
Prof Jose Villadangos
Further reading:
HEG McWilliam, … and JA Villadangos. 2016. The intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1. Nat. Immunol. 17: 531-537. PMID: 27043408
HEG. McWilliam, … and JA Villadangos. 2020. Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens. Proc. Natl. Acad. Sci. USA 117: 24974-24985. PMID: 32958637
HJ Lim, … , JA Villadangos* and HEG McWilliam*. 2022. A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells. J. Cell. Biol. 221: e202110125. PMID: 36129434
HEG McWilliam and JA Villadangos. 2023. MR1 Antigen Presentation to MAIT and other MR1-Restricted T Cells. Nat Rev Immunol. In press (14/08/2023).
Contact project supervisor for further
information and application enquiries
Villadangos Group
6 vacancies
The Villadangos group studies the first event that triggers adaptive immune responses: the presentation of pathogen or tumour antigens to T cells by Dendritic Cells, B cells and Macrophages. We are characterizing the development, regulation and impairment of antigen presenting cells by pathogens, inflammatory mediators and tumours. We are also dissecting the biochemical machinery involved in antigen capture, processing, and presentation. We use this knowledge to understand how T cell-dependent immunity is initiated and maintained and apply it to design better vaccines and immunotherapies against infectious agents and cancer.
All our projects are open to Honours/Master of Biomedical Science students and PhD/MPhil graduate researchers
Villadangos Group Current Projects
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The immune signature of sepsis
PhD/MPhil, Master of Biomedical Science, Honours
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Regulating macrophage 'eating' for cancer and pathogen control
PhD/MPhil, Master of Biomedical Science, Honours
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Trogocytosis: a novel communication system between cells of the immune system
PhD/MPhil, Master of Biomedical Science, Honours
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Improving the formation of protective immunity against human viruses
PhD/MPhil, Master of Biomedical Science, Honours
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A novel link between metabolism and immune function: O-GlcNAc glycosylation
PhD/MPhil, Master of Biomedical Science, Honours
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Immunoregulatory functions of the MARCH family of ubiquitin ligases
PhD/MPhil, Master of Biomedical Science, Honours
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Understanding the causes of immune paralysis and secondary infections in sepsis and trauma patients
PhD/MPhil, Master of Biomedical Science, Honours
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Harnessing the power of RNA vaccines and therapeutics
PhD/MPhil, Master of Biomedical Science, Honours
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MR1 – a molecular detection system for bacteria
PhD/MPhil, Master of Biomedical Science, Honours
Research degrees at the Doherty Institute are administered by the University of Melbourne.