From hybrid to Tribrid: A refurbished Orbitrap Eclipse Tribrid Mass Spectrometer

Summary This proposal seeks funding toward the purchase of a refurbished Orbitrap Tribrid mass spectrometer from ThermoFisher, with Easy ETD option. The resulting combination of fast cycle times, accurate, high-plex quantitation, ultra-high resolution, high sensitivity and multiple ion fragmentation modes is unavailable to the major user group for this proposal yet would allow fundamental enhancements in quantitative protein-based mass spectrometry experiments in support of a number of NIH funded research programs at UC-Irvine. Specific projects that will be enhanced include: An investigation of the molecular structure of Vaccinia virus (Dr. Gershon), global cellular responses to polio and rhinovirus infection (Dr. Semler), molecular signaling in spinal cord regeneration (Dr. Anderson), protein secretomes during neural stem cell development in Huntington’s disease (Dr. Thompson), programs during early brain development (Dr. Cramer), protein secretion within a “tumor on a chip” (Dr. Hughes), targeted unnatural amino acid incorporation (BONCAT) into neuritic plaques in an Alzheimer’s mouse model (Dr. Glabe), new paradigms in single-cell virology (Dr. Drayman), mechanisms of T cell exhaustion (Dr. Tinoco), the role of cell surface glycosylation in neural stem cell differentiation (Dr. Flanagan), novel approaches to spatial proteomics (Dr. Shi) and the molecular biology of human vision (Dr. Palczewski). In tests, Tribrid performance was up to 10-fold superior to that of the currently available instrument in key metrics, and the ETD option will be applicable for 56% of the above-listed users. The proposed instrument will be housed in a facility space under oversight from a supervisory committee with external member Dr. James Wohlschlegel (UCLA), and internal committee members representing the major relevant biomedical research entities at UC- Irvine. 26 current NIH-supported and 36 total active research grants related to human health spanning seven departments in at least two schools of UC-Irvine are expected to benefit critically from the capabilities of the proposed instrument. The requested instrument would provide a synergistic boost to interdisciplinary biomedical research capabilities within the Schools of Medicine and Biological Sciences at UC-Irvine.