Careers & Students

Building a mouse to study human autoimmune T cell responses in type 1 diabetes

Building a mouse to study human autoimmune T cell responses in type 1 diabetes

PhD/Honours project

Advances in the immunology of autoimmune, or type 1, diabetes have relied heavily upon the NOD mouse.  While the mouse is a useful model it doesn't’ allow us to directly understand how the human autoimmune response that causes type 1 diabetes works. The aim of this project is to develop and use a mouse model that incorporates critical components of the human autoimmune response against proinsulin. In collaboration with Dr Serreze at the Jackson Laboratories in the USA we have generated a mouse that expresses human HLA-DQ8 and human proinsulin.  We are currently working towards introducing human T cells, isolated from the residual pancreatic islets of organ donors who suffered from type 1 diabetes, into these mice. The goals of this project are to test the T cells we know recognize human proinsulin (Pathiraja et al. Diabetes 2015) to see if they cause diabetes in the NOD mouse. If any of these T cells cause diabetes in the NOD mouse it will confirm that human islet-infiltrating CD4+ T cells are pathogenic and provide a long-sought model of pathogenic human autoimmune responses. Such a model is essential for developing effective antigen specific therapies to prevent and treat type 1 diabetes in humans. The student working on this project will develop skills in human and murine immunology, mouse genetic manipulation, in vivo immune assays, flow cytometry and molecular biology techniques.

Supervised by:

  • A/Prof Stuart Mannering
  • Disease Focus:

  • Type 1 diabetes
  • Research Unit:

  • Human T cell