Overall Plan: Summary The overall goal of this Center of Biomedical Research Excellence (COBRE) application is to strengthen the biomedical research infrastructure in Montana with a focus on the central, multi-disciplinary theme of Integrated Biomedical and Rural Health Research, a subject that is both sufficiently broad to enable recruitment of diverse faculty and sufficiently focused to build cohesiveness around a common goal to address rural health in a multi- disciplinary fashion that includes basic, translational and clinical studies. The Center for Biomedical and Rural Health Research encompasses mentorship and collaboration between faculty in the established partnership between the McLaughlin Research Institute, the Touro University College of Osteopathic Medicine - Montana, and the Benefis Healthcare System, the largest comprehensive provider in central Montana extending across 38,000 square miles with outreach services present in 94 percent of Montana’s counties. We focus on building capacity in research on health problems that are especially of concern and/or prevalence in rural environments with three specific aims to: 1) Enhance the success of Research Project Leaders (RPLs) along the integrated trajectory from bench to translational animal models, to clinical applications. 2) Recruit a minimum of eight additional faculty, in Phase I, as RPLs and Pilot Project Investigators (PPIs) to increase the number of investigators, and their scope and impact, in integrated biomedical research. 3) Build and maintain two critical core facilities that support expansion of research infrastructure. To accomplish our aims, we present four initial projects focused on neurological diseases, diseases that are common and distinctively devastating, in rural environments: Neutrophil apoptosis in Alzheimer’s disease pathogenesis, age-related macular degeneration and exosome release, misfolded SOD-1 and α-synuclein proteins in idiopathic Parkinson’s disease (PD), and comprehensive phenotypic profiling of Chronic Wasting Disease (CWD). Each project is led by a new or an early- stage investigator with an engaged mentoring team specifically tailored to their career development. Supporting these projects are two cores: The Administrative Core and the Gene Editing and Mouse Models Assessment (GEMMA) Core. This application is significant as it establishes a unique and sustainable center that serves the two primary purposes of supporting career development of new and early-stage investigators in a unique geographical and socio-cultural area of Montana and of advancing our understanding of conditions of special concern and/or prevalence in rural communities. The application is innovative in multiple aspects but especially as it: 1) Taps into the strengths and resources of an extensive and under-utilized sector of the healthcare community through a partnership between an independent nonprofit research organization, an osteopathic medical campus and a rural-serving hea...