We propose to continue development and support for the UltraScan-III (US3) software suite and develop new code and methods to address challenging biomedical research questions that can be solved with the latest instruments available for analytical ultracentrifugation and at beamlines for small-angle X-ray and neutron scattering experiments (SAXS/SANS) experiments. UltraScan is a comprehensive toolkit for the analysis of data from hydrodynamic experiments and simulations. Such experiments include analytical ultracentrifugation, SAXS/SANS, as well as bead modeling simulations. Support for this project will assure continued availability of a mature multi-platform analysis suite with important and unique capabilities not found in any other software packages. Chief among them are tight integration of supercomputing capabilities, LIMS support for collaboration, and specialized analysis routines. US3 enjoys widespread use in the AUC and SAXS/SANS communities, and offers the most robust optimization and simulation algorithms available, resulting in unmatched detail. UltraScan provides the highest throughput, a flexible, modern GUI, and a comprehensive list of analysis routines. Proposed developments include automated data acquisition and analysis workflows, improvements in the fitting of floating data, improved two-dimensional grids, support for density distribution analysis critical for the accurate characterization and quantification of viral vectors, lipid nanoparticles loaded with cancer drugs or nucleic acids, and other vectors used for the delivery of medicines or CRISPR technology.

Public Health Relevance

The proposed work will further develop and continue to maintain the UltraScan software suite, which contributes to the analysis of biophysical solution data with unmatched resolution and efficiency. Among the proposed developments are codes to improve analysis efficiency, to support automated data acquisition from the Beckman-Coulter Optima AUC?TM instrument, and measuring the loading efficiency of lipid nanoparticle vectors for medicines, siRNA and CRISPR technology. These efforts are highly relevant for many current NIH and NSF investigations, support the development of therapeutics against any disease studied on the molecular level, and contribute important tools for studies into the mechanisms of aging, cancer, HIV, neurodegenerative diseases and help with the testing of drugs and their interactions with drug targets.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Biodata Management and Analysis Study Section (BDMA)
Program Officer
Gindhart, Joseph G
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Montana
Schools of Arts and Sciences
United States
Zip Code
Kim, Haram; Brookes, Emre; Cao, Weiming et al. (2018) Two-dimensional grid optimization for sedimentation velocity analysis in the analytical ultracentrifuge. Eur Biophys J 47:837-844
Williams, Tayler L; Gorbet, Gary E; Demeler, Borries (2018) Multi-speed sedimentation velocity simulations with UltraScan-III. Eur Biophys J 47:815-823
Johnson, Courtney N; Gorbet, Gary E; Ramsower, Heidi et al. (2018) Multi-wavelength analytical ultracentrifugation of human serum albumin complexed with porphyrin. Eur Biophys J 47:789-797
Wang, Zhonghua; Bhattacharya, Akash; White, Tommy et al. (2018) Functionality of Redox-Active Cysteines Is Required for Restriction of Retroviral Replication by SAMHD1. Cell Rep 24:815-823
Zhang, Jin; Pearson, Joseph Z; Gorbet, Gary E et al. (2017) Spectral and Hydrodynamic Analysis of West Nile Virus RNA-Protein Interactions by Multiwavelength Sedimentation Velocity in the Analytical Ultracentrifuge. Anal Chem 89:862-870
Fan, Yanlin; Guo, Yusong R; Yuan, Wang et al. (2017) Structure of a pentameric virion-associated fiber with a potential role in Orsay virus entry to host cells. PLoS Pathog 13:e1006231
Kim, Sun Kyung; Barron, Lindsey; Hinck, Cynthia S et al. (2017) An engineered transforming growth factor ? (TGF-?) monomer that functions as a dominant negative to block TGF-? signaling. J Biol Chem 292:7173-7188
Karabudak, Engin; Brookes, Emre; Lesnyak, Vladimir et al. (2016) Simultaneous Identification of Spectral Properties and Sizes of Multiple Particles in Solution with Subnanometer Resolution. Angew Chem Int Ed Engl 55:11770-4
Gray, Felicia; Cho, Hyo Je; Shukla, Shirish et al. (2016) BMI1 regulates PRC1 architecture and activity through homo- and hetero-oligomerization. Nat Commun 7:13343
Wong, Sarah J; Gearhart, Micah D; Taylor, Alexander B et al. (2016) KDM2B Recruitment of the Polycomb Group Complex, PRC1.1, Requires Cooperation between PCGF1 and BCORL1. Structure 24:1795-1801

Showing the most recent 10 out of 13 publications