Understanding how interferons are involved in autoimmune diabetes
- Research Opportunity
- PhD, Masters by Research, Honours, Master of Biomedical Science
- Project Status
- Medicine and Radiology
- St Vincent's Hospital
|A/Prof Helen Thomas||Personal web page|
|Dr Tom Brodnicki||Personal web page|
Type 1 diabetes is caused by T-cell-mediated destruction of the insulin- producing beta cells in the pancreatic islets. There is a significant gap in our knowledge of the events leading to initiation of autoimmune diabetes. Our preliminary data suggest that interferons (IFN) are essential in this process. There are three types of interferons: type I (IFNα/β), type II (IFNγ) and type III (IFNλ). Each interferon signals through a distinct receptor, but with overlapping signal transduction pathways. We know that IFNγ promotes beta cell-T cell interaction by upregulating MHC class I. Type I IFN stimulates a transcriptional signature in the islets. Type I IFN is also strongly implicated in other autoimmune diseases such as systemic lupus erythematosus.
Previous data suggest that interferons may have overlapping roles in the pathogenesis of diabetes. We have therefore generated mice lacking one, two or all three interferon receptors (IFNAR1, IFNGR1 and IL-28Ra) in non-obese diabetic mice using CRISPR/Cas9 technology. We will study the contribution of each type of interferon to gene expression changes in the islet, and to development of diabetes. This will be done using flow cytometry, immunohistochemistry, quantitative RT PCR and by monitoring mice for diabetes development.
Inhibitors of interferon signalling are in clinical use for other diseases. To use these drugs effectively in patients, more needs to be known about when and how interferons act in autoimmune disease.
This project is conducted in St Vincent’s Institute of Medical Research, Islet Biology Unit
School Research Themes
PhD, Masters by Research, Honours, Master of Biomedical Science Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research
For further information about this research, please contact a supervisor.