Incontinence affects almost 66 million people in the European Union. The Over Active Bladder (OAB) symptom complex is one of the major causes for incontinence, with a large number of affected persons and immense associated health care costs. The causes for the over active bladder contractions, underlying the urinary urgency of OAB are unknown, and current treatments are only partially effective. This collaborative and translational project, involving interaction between experimental and clinical urology scientists will focus on OAB and will characterize the different interacting cellular components and signaling systems in the wall of normal urinary bladders and OAB. The release of local mediators in the bladder wall, the properties of a newly described cell type (the interstitial cells, which may play a role in bladder over activity), the sensory signaling pathways (TRPV1-receptors), the receptor interaction and cellular communication are considered in order to create an integrated view on the mechanisms of bladder over activity. A strong emphasis is put on interaction between basic science and clinical applications, using a translational approach involving both specific animal models and human tissue from patients with defined urodynamic information. Several ethical and logistic issues with the use of human tissue are specifically addressed. An important further aspect of the experiments on human tissue is a direct analysis of the links between genetic and the urodynamic data of the patients, using unique biobanks. This will allow us further insight into the mechanisms of disease and possibly to identify new therapeutic targets. In close collaboration with a small company, we will develop an innovative potential physical therapy to affect bladder function. We will develop novel pharmacotherapeutic strategies and diagnostic tools, based on the characterization of cell properties, gene expression, receptors signaling systems of the bladder wall.