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Prevention and definition of autoimmunity through dipeptidyl-peptidase IV signaling

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.

Call for proposal

FP6-2002-MOBILITY-7
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Coordinator

INSTITUT OF MOLECULAR BIOTECHNOLOGY OF THE AUSTRIAN ACADEMY OF SCIENCES
Address
Dr Bohrgasse 3-5
Vienna
Austria