Objective Type-1 diabetes remains one of the most devastating childhood disease of the day. Despite over acentury of research into the condition diagnosis still carries with it a sentence to lifelong daily insulininjection. Despite its prevalence, medicine has yet t o offer preventative therapy for the condition.Dipeptidyl peptidase IV (DP IV) is a ubiquitous multifunctional membrane ectopeptidase withparticularly high expression levels on the endothelial lining of the vasculature and on the surface ofimmune cells. Th e aims of the current investigation are built upon several pieces of evidence:i. immune cells expressing DP IV have been implicated in the process of autoimmunityii. DP IV-inhibitors have been shown to suppress immune activationiii. DP IV-inhibitors have b een shown to augment the actions of the ß-cell enhancing peptides GIPand GLP-1, effecting enhanced secretory function, neogenesis and cell survivalThe aims of the current application are three-fold: to use DP IV-inhibitors as tools to both pry into therole of DP IV in development and function of cellular immunity; to investigate the unique therapeuticpotential of DP IV-inhibitors (combined immunosuppression and ß-cell enhancement) in the treatmentof type-1 diabetes mellitus; and, through establishment of an embryonic stem cell line containing atype-1 diabetes (NOD) genome, to generate NOD mice with a specific deletion of the DP IV gene. Inaddition to possibly establishing the first preventative therapy for type-1 diabetes mellitus, fulfillmentof these goals would represent major advances in a number of areas; first, deepening ourunderstanding of immune cell development and function as well as autoimmunity, whilst providingthe scientific community with a powerful tool for the investigation of the genetic under pinnings for type-1 diabetes. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesmedical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicineimmunologymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsgenomes Keywords Autoimmunity Dipeptidyl Peptidase IV Enzyme inhibition Hematopoietic cells Knockout mice NOD-mouse Proteomic screen Type-1 diabetes Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.3 - Marie Curie Incoming International Fellowships (IIF) Call for proposal FP6-2002-MOBILITY-7 See other projects for this call Funding Scheme IIF - Marie Curie actions-Incoming International Fellowships Coordinator INSTITUT OF MOLECULAR BIOTECHNOLOGY OF THE AUSTRIAN ACADEMY OF SCIENCES EU contribution No data Address Dr Bohrgasse 3-5 VIENNA Austria See on map Total cost No data