Rossjohn Laboratory

Understanding immune function and dysfunction.

Dr. Wael Awad
ARC DECRA Research Fellow

Metabolite mediated T cell immunity

The immune system fights off invading pathogens by sensing foreign fragments “antigens” on the surface of the infected host cells. Using multidisciplinary approaches, our team is investigating the roles of the poorly understood classes of antigens “small molecule metabolites” in the T cell immunity. During microbial infection of mammalian cells, MHC-1 class I related molecule “MR1” binds to and presents vitamin B precursors, derived only from the microbial biosynthesis of riboflavin, on the cell surface. These MR1-Antigen complexes are recognised by subsets of MR1-restricted T cells, with the majority being Mucosal-Associated Invariant T (MAIT) cells. MAIT cells have recently been shown to play key roles in antimicrobial immunity, autoimmunity, cancer, and tissue repair.

The overarching aim of our team is to provide ground-breaking findings on (i) the cellular machinery that modulates MR1-metabolite processing; (ii) metabolite presentation and (iii) T cell recognition of these metabolic antigens. Our underlying approach is to express and purify proteins, and determine the three-dimensional protein structure using the expertise in x-ray crystallography. These are complemented by multi-disciplinary and highly innovative approaches including molecular biology, protein biochemistry, biophysics and cellular immunology. Ultimately, such studies improve our understanding of the molecular determinants of T cell immunity and pave the way for the development of innovative therapeutics based on selective modulation of MAIT cell immunity

Research projects

  1. To explore the molecular basis of MR1-Antigen processing and loading.
  2. Discovery of novel microbial antigens that could modulate MAIT cell Functions.
  3. Non-microbial metabolites and T cell immune surveillance.

Supervision interests

We are seeking motivated and talented people to synergise with the team to make new and seminal discoveries surrounding the MAIT-MR1-metabolites functions.

Multiple projects are available or download Honours projects here

Full list of publication