A transformative Orbitrap Tribrid mass spectrometry system for advanced quantitative proteomics at the UMKC Biological Mass Spectrometry and Proteomics Facility - Project Summary / Abstract The proposal requests funding for a new shared-use Thermo Scientific Orbitrap Fusion Lumos mass spectrometer with EASY-nLC 1200 system ultra-high performance liquid chromatography system to enable the acquisition of the highest quality proteomics data sets at the University of Missouri – Kansas City (UMKC). The proposed instrumentation will be an integral part of the UMKC Biological Mass Spectrometry and Proteomics Facility (BMSPF) located in UMKC’s School of Medicine. Currently, all proteomics experiments at UMKC are analyzed using a single, refurbished Thermo Scientific Q Exactive Plus mass spectrometer purchased in 2016; this is the only high resolution proteomics-capable mass spectrometer available to UMKC investigators. It lacks the crucial advanced analytical options required for NIH-funded research of BMSPF users. The requested instrumentation will address this critical need by providing the substantial technological upgrades required for health-related projects focused on elucidating the protein contributions to human diseases and forming the basis for novel therapeutic strategies pursued by NIH-funded investigators at UMKC. These vital features include much faster scan speeds possible with the ultra-high field Orbitrap, and exclusive scan modes such as MultiNotch for providing the highest quantitative accuracy in whole proteome analysis in multiplexed samples for high throughput, and also the coordinated use of the unique tribrid mass spectrometer components to increase proteome coverage for more comprehensive data sets and deep “label free” quantitation. These urgently needed features are uniquely possible using the proposed instrumentation, and are required for the proposal’s 23 investigators, of which 13 are funded by grants from 9 different NIH institutes. By implementing these new technologies featured on the Orbitrap Fusion Lumos, BMSPF will permit breakthrough research that requires analysis of the scant amounts of material available in critical tissue samples and affinity purified materials our investigators prepare, identifying proteins that are implicated in disease using quantitative proteomics of the highest accuracy. The proposed system will serve a diverse and increasing community of NIH-funded researchers at UMKC meeting the current increased and future needs for characterization and quantitation of specific proteins, protein complexes, and whole proteomes, as well as modernize training in health-related research. The proposed equipment will accelerate research progress and enhance the rigor, quality and breadth of research results determining causes, mechanisms of action and generate data of the highest impact possible. Overall, these advancements will allow NIH-funded UMKC investigators in need of this instrumentation conduct research on diseases that affect significant and increasing portions of the U.S. population including minorities affected by disparities in health care delivery, to determine the underlying protein contributions to human disease, help design future therapeutics and improve health care.