Amino acid transport: a new target for regulating immune cell function and preventing type 1 diabetes
A major challenge for preventing type 1 diabetes (T1D) is stopping the immune system from destroying the insulin-producing beta cells in the pancreatic islets. While autoreactive T cells specifically target the beta cells, other immune cells (eg macrophages, dendritic cells) prime and maintain the inflammatory milieu within the islets. A potential set of therapeutic targets are nutrient transporters because they can alter immune cell responses by regulating access to nutrients. We have established mutant mice for one of these transporters and shown that these mice have an increased incidence of T1D. Intriguingly, this transporter only transports aromatic amino acids (AAA) across cell membranes.
The goal of this project is to determine how this unique transporter affects immune cell function and T1D pathogenesis. Briefly, we will use our mutant mice to identify which immune cell responses are regulated by this transporter, as well as intracellular signalling pathways that are affected by changing the AAA levels in immune cells.
This project will employ a variety of molecular and cellular techniques, including CRISPR/Cas9 gene editing, tissue culture, gene expression analysis and various immunological assays. The results are anticipated to help reveal a new mechanism for regulating immune cells that cause type 1 diabetes.
*In addition to SVI Top-Up Scholarships, students working on this project may be eligible for top-up awards from the Australian Juvenile Diabetes Research Foundation.
Dr Tom Brodnicki
Prof Helen Thomas
Type 1 diabetes
Our group investigates how certain genes affect immune cell responses that are important for preventing autoimmune and infectious diseases. Studying such genes in humans is difficult due to genetic heterogeneity and tissue availability. Our strategy is to take advantage of different mouse models to discover disease susceptibility genes. We employ a combination of gene editing techniques and transcript profiling, along with immune cell assays and protein functional studies. Our ongoing work has identified unsuspected genes and unique molecular mechanisms that regulate destructive immune responses and prevent disease pathology. Our ultimate goal is to turn these findings into new therapeutic targets for treating autoimmune and infectious diseases.
For further information about this project, contact: