Research objectives and content
The application's goal is the identification of molecular mechanisms that are responsible for pancreatic islet infiltration and Beta-cell destruction in insulin-dependent diabetes mellitus (IDDM). The project is divided into two parts: 1.) Determination whether an antigen-specific contact between T-cells and Beta-cells is required for Beta-cell destruction. Using transgenic mice that express a transgenic T-cell receptor specific for influenza hemagglutinin (TCR-HA) and HA in alfa-islet cells under the control of the glucagon promoter (GLU-HA), it will be analyzed if TCR-HAxGLU-HA mice develop diabetes like TCR-HAxINS-HA mice that express HA under the control of the insulin promoter. 2.) Identification of potential mediators of infiltration and Beta-cell destruction analyzing the transcription of candidate genes (chemokines, cytokines and others) in islets that undergo either infiltration or Beta-cell destruction. By studying different animal models of IDDM it will be tested if the findings are generalizable.
For the first time it will be possible to distinguish clearly if Beta-cell death is an antigen-dependent or independent process and which factors are responsible for pancreatic infiltration as well as which are responsible for Beta-cell destruction. Based on these findings new diagnostic and therapeutic strategies can be developed for monitoring and treatment of IDDM already at an early, possibly reversible stage.
Training content (objective, benefit and expected impact)
Learning of new methods and work with another autoimmune model. Finally, the training will provide the basis for a scientific career in Europe. Links with industry / industrial relevance (22)
Temporary consulting agreement with Mirieux, France.