PROJECT SUMMARY/ABSTRACT This application requests funds to purchase a Sierra SPR-24 Pro (Bruker), a high-throughput surface plasmon resonance biosensor (HT-SPR). The instrument will replace a deprecated Biacore 4000 (Cytiva) that has been in operation for over nine years. SPR is an exquisitely sensitive method for measuring binding interactions between an immobilized molecule and a solution-phase molecule in real time. The measured signal is proportional to the change in mass, allowing determination of binding stoichiometry as well as binding/unbinding kinetics and equilibrium binding constants. The instrument will be placed in the UCSF Small Molecule Discovery Center (SMDC), a state-of-the-art core facility for high-throughput screening, chemical biology, and drug discovery. Nineteen investigators will use the instrument over the first two years. Nine NIH-funded major users require the instrument immediately to characterize protein-protein and protein/small-molecule interactions and to discover new probes. Areas of biology include: 1) protein homeostasis - AAA+ ATPases in cancer and rare disease, chaperones in cancer and neurodegeneration, ubiquitin ligases in virology; 2) regulatory enzymes – demethylases in cancer, nSMase in immuno-oncology; 3) coronavirus – antibodies and designed proteins as drugs and diagnostics; 4) membrane proteins - extracellular proteases in cancer, iron regulation in disease. Ten minor users provide additional diversity and represent potential major users in the future. The SPR-24 will replace a 9-year old Biacore 4000 that is now obsolete for current and anticipated usage. Specifically, 1) the instrument is no longer supported by Cytiva and key parts are no longer available, 2) the system is ill-suited to small projects, leading the SMDC to turn away several users, and 3) data management and data analysis software are inconvenient for large projects, resulting in significant time spent transferring files to third-party software. The diverse research projects require SPR instrumentation that is sensitive, robust, and allows flexibility in experimental design. We researched four instruments; while all are sensitive enough for the needs of the projects, we determined that the SPR-24 included several ideal features. First, the chip architecture provides eight simultaneous injections across three surfaces, allowing a high degree of multiplexing; additionally, samples can be selected from the plate through a flexible user interface, which facilitates small experiments. The cost of the instrument is highly favorable and the cost-of-use is competitive. Finally, the instrument is space efficient now and automatable later; it has internal capacity to hold two 384-well plates and can be connected to a robotic plate handler that will be purchased if future projects require it. The SMDC has a thirteen-year track record of successfully managing high-end equipment using an established web-based calendar and recharge system. An expe...