Project: MR1 – a molecular alarm system for bacterial infection
Villadangos Group
This project seeks to characterise an evolutionarily conserved system of detection of pathogen metabolites that is used by our immune system to protect us against infection and repair damaged tissues. The centrepiece of this mechanism is a highly specialised molecule called MR1.
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.
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. 2024. MR1 Antigen Presentation to MAIT and other MR1-Restricted T Cells. Nat. Rev. Immunol. 24: 178-192. PMID: 37773272
Contact project supervisor for further
information and application enquiries
Villadangos Group
6 vacancies
![](https://www.doherty.edu.au/uploads/banner_bg_img/jose_villandangos.jpg)
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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Improving the formation of protective immunity against human viruses
PhD/MPhil, Master of Biomedical Science, Honours
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MR1 – a molecular alarm system for bacterial infection
PhD/MPhil, Master of Biomedical Science, Honours
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Regulation of Complement by Membrane Receptor Ubiquitination
PhD/MPhil, Master of Biomedical Science, Honours
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Harnessing the power of RNA technology for vaccines and therapeutics
PhD/MPhil, Master of Biomedical Science, Honours
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Investigating the role of dendritic cell O-GlcNAcylation in adipose tissue homeostasis and immune function
PhD/MPhil, Master of Biomedical Science, Honours
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Understanding the causes of immune paralysis and lethal secondary infections in sepsis and trauma patients
PhD/MPhil, Master of Biomedical Science, Honours
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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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A novel link between metabolism and immune function: O-GlcNAc glycosylation
PhD/MPhil, Master of Biomedical Science, Honours