Project Summary Overactive bladder (OAB) is a symptom complex that is highly prevalent and negatively impacts quality of life. Multiple mechanisms likely contribute to OAB symptoms, though current therapies only target a few potential mechanisms. Recent evidence suggests that the urinary tract, which traditionally has been thought to be sterile in the absence of a clinically identifiable infection, actually harbors a variety of microbes, known collectively as the urinary microbiota, even when clinical cultures are negative. These microbial communities appear to be altered women with urge urinary incontinence (wet OAB), however it is unknown if the urinary microbiota are also altered in the broader patient population with OAB without incontinence (dry OAB) or how the urinary microbiota contribute to OAB symptoms. This proposal aims to determine if the urinary microbiota are also altered in women with dry OAB (Aim 1). Additionally, the proposed study also aims to lay the ground work for understanding the functional contribution of the urinary microbiota to OAB. In other body sites, commensal microbes contribute to host health and disease through interactions with the immune system and their metabolic activity. The proposed studies will identify interactions with the host immune system by identifying immunoglobulin-A associated microbes (Aim 2) and identify metabolic products of the urinary microbiota through metabolomics studies (Aim 3). Together, information gained through completion of these aims will lead to key insights that will guide biomarker and mechanistic studies aimed at improving the clinical management of patients with OAB. Candidate: Dr. Karstens has a unique background including training in bioinformatics and analytical chemistry. Her long-term goals are to apply this knowledge to understand the mechanisms underlying complex urinary tract disorders to streamline therapeutic options for women suffering from these conditions. Career development plan: The career development plan includes hands-on and didactic training to gain expertise in women’s health and clinical research, as well as expand her knowledge in the molecular techniques required to understand the function of the urinary microbiota. Environment: Her interdisciplinary mentorship team brings together expertise in bioinformatics (Dr. McWeeney), urogynecology (Dr. Gregory), microbiology (Dr. Wolfe), immunology (Dr. Rosenbaum), and host-microbe interactions (Dr.Braun). Training will be completed at Oregon Health & Science University, a leading biomedical research and training institution in the state of Oregon. OHSU has an excellent translational research and training infrastructure to facilitate the successful transition to an independent career in translational bioinformatics research focused on understanding bladder disorders. !