The Center of Biomedical Research Excellence in Biomolecular Structure and Dynamics (CBSD COBRE) at the University of Montana (UM) supports research that applies the methods and concepts of biophysics, structural biology and chemistry to understand the mechanistic basis of biological processes in health and disease. The CBSD COBRE draws from a pool of about 60 faculty members from the basic and biomedical sciences in the College of Humanities and Sciences and the College of Health. This phase III proposal builds on the successes of phases I and II of COBRE support for the CBSD that have led to the hiring of seven new faculty and early career support for an additional nine UM faculty. The direct COBRE support for their research efforts, the COBRE-supported research cores that underpin their research programs and the vibrant seminar and mentoring programs sponsored by the CBSD COBRE have propelled these early career investigators to success. As a cohort, they have been awarded 39 grants that brought in $16.8 million to support their research and have generated 83 well-cited peer-reviewed publications. During phases I and II, the CBSD COBRE has supported four research cores, the Integrated Structural Biology Core (ISBC), which provides gene to structure services, the BioSpectroscopy Core Research Laboratory (BCRL), which gives CBSD researchers access to state-of-the-art fluorescence lifetime and imaging instrumentation, the Molecular Computation Core Facility (MCCF), which provides molecular docking, drug discovery and molecular dynamics (MD) platforms, and the Mass Spectrometry Core Facility (MSCF), which applies proteomic and metabolomic approaches to CBSD research problems. The growth in the number of CBSD researchers afforded by investment in early career investigators and strong investment in research core infrastructure during phases I and II of COBRE support, which has included more than $2 million in new equipment resulting from extramural equipment grants, has positioned the CBSD well to attain long-term sustainability with phase III COBRE support. The CBSD COBRE will use the phase III COBRE to pursue three specific aims designed to sustain the CBSD beyond phase III. With specific aim 1, we will continue to expand the cutting-edge capabilities of our research cores by carefully prioritizing COBRE and institutional resources so that the cores respond to the needs of their users and by continuing to vigorously pursue extramural funding for equipment that enhances core infrastructure. Specific aim 2 will evolve the role of the Administrative Core to lead the CSBD to sustainability through strategic financial planning and ongoing mentoring programs that keep CBSD researchers across career stages at the leading edge of their research areas. Finally, specific aim 3 will develop a Pilot Project program designed to incentivize new scientific directions that not only use, but also expand the technical capabilities of our research cores. This carefully-designed framework will ensure the long-term sustainability of the CBSD and the vital research community that it supports.

The Center for Biomolecular Structure and Dynamics (CBSD), an NIH Center of Biomedical Research Excellence, supports research programs that use biophysical and structural biology methods to understand the underlying mechanisms of normal and pathological physiological processes. This proposal will fund the instrumentation-intensive research core facilities necessary to conduct this research and programs designed to sustain the center over the long term so that CBSD researchers can continue to lay the groundwork to discover new therapies for the treatment of human pathogens, diabetes, neurodegenerative diseases, and cancer.