Acquisition of a Beckman-Coulter Optima Analytical Ultracentrifuge Project Summary/Abstract: This proposal details a funding request for a Beckman-Coulter Optima analytical ultracentrifuge with multi- wavelength UV-Visible absorption and Rayleigh interference detection optics, with necessary accessories. The instrument will be installed in the Johnson Research Foundation Structural Biology and Biophysics Core (JRFSBBC) Facility that is overseen by the Department of Biochemistry and Biophysics at the Perelman School of Medicine of the University of Pennsylvania. The instrument will support NIH-funded research by investigators at Penn and other research institutions in the Greater Philadelphia region, collaborative research with NIH and NSF-funded researchers from across the US where similar technology and expertise is not available, and the training of graduate students and postdoctoral trainees. This new instrument will replace a ~25-year-old Beckman XL-A analytical ultracentrifuge (AUC) that currently serves the core. The new instrument represents an important advance in analytical ultracentrifugation and enables the application of arising methods that leverage multiwavelength data collection; this is currently not possible with the older instrument. These technical advances include improved wavelength reproducibility, vastly improved signal-to- noise, and faster scanning rates, which together will provide superior precision in the study of the thermodynamics of macromolecular associations and shape in solution. The research projects that will be advanced are broad in scope and all high-impact, including HIV drug discovery, cancer, antibiotic resistance, integral membrane protein drug targets, neurodegenerative disorders, and chromatin structure. The technology sought is relatively new, with few such instruments available in the academic setting nationwide (since early 2017) and is expected to impact a large group of intra- and extramural users. The instrument will be managed by the very experienced team at the JRFSBBC, which was established in 2016, within an already large and robust research environment.