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How does amino acid supply affect immune cell function and the development of autoimmune disease?

How does amino acid supply affect immune cell function and the development of autoimmune disease?

PhD/Honours project

All cells, including immune cells, depend on extracellular nutrients to support biochemical processes required for proper function. The intracellular concentration of amino acids, in particular, can alter immune cell responses. Amino acids are important not only for protein biosynthesis, but also act as signaling molecules that modulate cell processes, including gene transcription, autophagy, and cell growth. Transporters are especially crucial for sensing and translocating amino acids across membranes, thus regulating their concentration and the signals they deliver. More importantly, these transporters represent potential drug targets to inhibit or enhance immune cell responses.
Current work in our lab is focused on the eight protein transporters that regulate the intracellular levels of the aromatic amino acids: tryptophan, phenylalanine and tyrosine. Altering the levels of these three amino acids can prevent self-destructive immune responses that contribute to autoimmune disease. Intriguingly, we have shown that disruption of one of these transporters (Slc16a10/TAT1) in mice increases the incidence of type 1 diabetes, an autoimmune disease in which the insulin-producing beta cells in the pancreas are destroyed by immune cells. The goal of this project is to determine how this and the other aromatic amino acid transporters regulate amino acid supply and affect the function of immune cells that contribute to disease pathogenesis.
This project will use a range of cellular and molecular techniques including cell-culture based assays, RNAseq, western blots, ELISAs, FACS and HPLC/mass spectrometry. In addition, we will use CRISPR/Cas9 mutagenesis to generate unique knockout cell lines and mice to further investigate the role of these transporters in the development of autoimmune disease. Students will also have the opportunity to work with our collaborators in the Immunology & Diabetes Unit at St Vincent's Institute, Division of Biomedical Science & Biochemistry at the Australian National University (Canberra), and the Institute of Physiology at the University of Zurich (Switzerland).
Supervisor: Dr Tom Brodnicki
Tel: 03 9231 2480 / Email: tbrodnicki@svi.edu.au

Supervised by:

  • Dr Tom Brodnicki
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Immunogenetics