Autoimmune diseases affect approximately 5% of Australians. Well known examples include type I diabetes, multiple sclerosis and rheumatoid arthritis. These diseases have unpleasant, and sometimes tragic, consequences for the affected person and are a costly burden on our health system. As treatment is often limited to managing symptoms, new therapies for autoimmune diseases are much desired.
The autoimmune diseases we study are described as "organ-specific", which means the unwanted immune response attacks either a single organ, or a collection of organs with some common feature. Organ-specific autoimmune diseases affect people with particular versions of genes in the "major histocompatibility complex" (MHC, also called human leucocyte antigen or HLA). MHC genes encode cell-surface proteins that present antigens to T cells. The main antigens presented by MHC molecules are peptides derived from the incomplete breakdown of proteins. Recent research showed that the risk of organ-specific autoimmune disease increases if the body fails to produce T-regulatory cells (Treg) that bind to a specific self-peptide/MHC expressed in the vulnerable organ (Ooi et al., Nature. 2017 May 11;545(7653):243-247).
Treg prevent autoimmune disease in nature but their therapeutic potential has yet to be harnessed. In this project, we will engineer T cell receptor-modified Treg (TCR-Treg). The effects of TCR-Treg therapy will be tested in vitro and in vivo in humanised mouse models.
Approaches, skills and techniques
- Transformation of plasmids into bacteria.
- Transduction of plasmids into mammalian cells.
- Retroviral transduction of mouse cells.
- Tissue culture.
- Flow cytometry and single-cell sorting.
- DNA sequence analysis.
- Handling, anaesthesia and immunisation of mice.
- Data management and presentation.
- Statistical analysis.
- Written and oral communication skills.
We will obtain preclinical data on the efficacy of TCR-Treg therapy in autoimmune disease and on whether TCR-Treg self-affinity affects the outcome of therapy.
Contact the supervisor for more information.