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 healthcare system, and 2) serves the dual purpose of providing unprecedented opportunities for expansion of biomedical research, talent recruitment and innovation in a rural region of the United States while also providing the physical and intellectual presence in situ that is required to increase public trust in biomedical research in the northern Rocky Mountain front and adjacent communities.

Overall Plan: Narrative The goal of this application is to establish the Center for Integrated Biomedical and Rural Health Research (CIB- RHR), a Center of Biomedical Research Excellence (CoBRE), that will enhance research infrastructure in a unique geographical, socio-cultural and economic region of the Rocky Mountain front and adjacent plains. The application is significant as it serves the two primary purposes of increasing the cohort of NIH funded investigators and of advancing our understanding of common health conditions of special concern and/or prevalence in a rural environment. The application is innovative in that the Center will provide unprecedented opportunities for talent recruitment and innovation in a rural underserved region of the United States, will establish the physical and intellectual presence required to increase trust in biomedical research in rural communities, and will serve as a potential model for other rural communities.