Research Projects

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

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