An absolute or relative loss of beta-cell mass and function underlie the development of type I and type 2 diabetes.Preventing beta-cell demise or restoring their number and function is a major therapeutic goal. However,development of novel diagnostic and prognostic tools, and of novel therapeutic modalities, is hampered by the limited knowledge of the molecular pathways that control beta-cell demise in diabetes, the production of new beta-cells from progenitors,or the replication and preserved function of mature beta-cells. Here,we propose an integrated approach to generate and exploit newcellular and animal models, and to develop novel investigative tools and biomarkers to gain new knowledge on the mechanisms of beta-cell function and demise in diabetes, to improve diabetes diagnostic and to identify novel therapeutic targets for drug development. To achieve this ambitious goal,we have established a consortium of leading European experts from universities and SMEs in the fields of beta-cell diabetes research,gene transfer technology, metabolom ics, biomedical imaging, bioinformatics and systemsmodeling. We propose a work plan composed of 5 scientific work packages structured to provide high levels of interaction within the network and with EFPIA partners.A management and administration work package will permit an efficient cooperation betweenuniversities, SMEs and industrial partners to ensure that the particular interests andneeds of pharmaceutical industry research are addressed.