Project Summary/Abstract: We request funding for a Beckman Optima AUC analytical ultracentrifuge equipped with Rayleigh interference and multi-wavelength UV-visible absorption detection, including required accessories, This instrument will be integrated into the Center for Biomolecular Structure and Dynamics (CBSD) at the University of Montana (UM) in Missoula and will support NIH funded research conducted by investigators from UM and affiliated research institutes, In addition, this instrument will be available for collaborative research projects with NIH and NSF funded investigators from across the US to support research projects at institutions where access to AUC expertise or instrumentation is not available, The Optima AUC, manufactured by Beckman-Coulter, Indianapolis, is the only commercially available analytical ultracentrifuge, and since 2017, replaces the Proteomelab XLI (no longer manufactured), Compared to the XLI, the Optima AUC features important technical innovations, such as much faster scanning rates, improved signal-to-noise, and much higher wavelength reproducibility, These innovations support a new class of multi-wavelength experiments, which permit spectral characterization in addition to the hydrodynamic separation of analytes, Together, these innovations provide higher capacity, much more precise measurements of stoichiometry and interaction thermodynamics when compared to the older instrument The instrument will be used to further develop and test AUC analysis software developed at UM by the Pl's research group, and to study macromolecular interactions in the solution phase to investigate questions addressing a wide variety of diseases and translational drug developments, ranging from opioid vaccine development, AAV gene therapies, lipid nanoparticles, HIV, breast cancer, neuro-degenerative diseases, bacterial antibiotics, as well as a number of basic research questions including germ cell development, receptor binding, protein structure and protein stabilization, bacterial DNA transformation, innate immunity, amyloid beta structure, fibril formation, and chromatin remodeling, The Optima AUC will be the first of its kind in Montana, therefore adding unique capabilities to biophysical characterization to our institution and the Northwestern Rockies region, benefiting a large group of intra- and extramural users, This instrument will be managed by the Pl, who is a world-leading expert in analytical ultracentrifugation and has published over 200 manuscripts dealing with AUC methods development The Pl is also the author of the UltraScan hydrodynamic modeling framework, the leading analytical ultracentrifugation software available today, The Pl has successfully managed multiple AUC facilities since 1996, has developed the worldwide UltraScan Science Gateway and UltraScan LIMS system, which provides remote HPC access to AUC users, He has contributed significantly to the AUC field over the past 30+ years by developing innovative modeling algorithms for AUC data, training a large number of new users worldwide, and by contributing to collaborative research projects from investigators across the US.

Project Narrative: A Beckman Optima AUC analytical ultracentrifuge is requested by the Center for Biomolecular Structure and Dynamics at the University of Montana in Missoula to support NIH-funded biomedical research, The instrument will provide high resolution hydrodynamic and optical characterization of biological macromolecules and their assemblies, The information gained is critical for the study of human disease and cancer, development of new drugs and vaccines, and to further the understanding of molecular processes occurring in the cell.