MR1 – a molecular alarm system that detects pathogen metabolites

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Number of Honour Places Available
2
Department
Microbiology and Immunology
Location
Doherty Institute
Primary Supervisor Email Number Webpage
Professor Jose Villadangos j.villadangos@unimelb.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr Justine Mintern jmintern@unimelb.edu.au Personal web page

Project Details

The antigen-presenting molecule MR1 alerts the immune system when an intracellular bacterial infection is taking place. It does this by capturing metabolite by-products from bacteria and presenting them at the cell surface to activate a type of leukocyte called mucosal-associated invariant T (MAIT) cells.  MAIT cells then directly kill the infected cell or secrete inflammatory cytokines to initiate protective immunity.

We have shown that MR1 captures pathogen metabolites inside the endoplasmic reticulum of the infected cell, but we do not know how the metabolites get there. The mechanisms that keep MR1 in a “receptive” state in the endoplasmic reticulum and that control the intracellular trafficking on MR1-metabolite complexes inside the cells are also unknown.

This project will characterize the MR1 antigen presentation system using CRISPR/Cas9 gene editing, biochemistry techniques, confocal microscopy, immunological assays and multiple pathogen infection models. The outcomes may reveal novel therapies to harness the MR1-MAIT cell axis against infection.

Further reading: HEG McWilliam et al (2016) Nat. Immunol., 17: 531-539; HEG McWilliam and JA Villadangos (2017) Trends Immunol. 38:679; HEG McWilliam and JA Villadangos (2018) Curr Opin Immunol 52:108.



Faculty Research Themes

Cancer, Infection and Immunology

School Research Themes

Cancer in Biomedicine, Infection & Immunity, Molecular Mechanisms of Disease



Research Opportunities

PhD, Masters by Research, Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Microbiology and Immunology

Research Group / Unit / Centre

Villadangos laboratory: Antigen presenting cells & molecules that initiate T cell immunity against pathogens and cancer

Research Node

Doherty Institute

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