PROJECT SUMMARY/ABSTRACT The broad, long-term goal of this proposal is to advance the long-term research of investigators at The Jackson Laboratory (JAX) and in the Maine research community by bringing to the Bar Harbor, ME campus a new ThermoFisher Scientific Orbitrap Fusion Lumos Tribrid Mass Spectrometer. Research at JAX focuses on discovering precise genomic solutions for disease and empowering the global biomedical community in our shared quest to improve human health. As part of this mission, JAX investigators are drastically increasing their use of mass spectrometry-based proteomics and metabolomics, as these approaches are key to many biological discoveries linking genomics to phenotype. The scale of these experiments is also increasing as investigators consider multiple mouse strains with different genetic backgrounds and/or outbred mouse models. Within-institution proteomics is critical for ensuring reproducibility among experiments and to enable cost- and time-efficient analysis. The current instrumentation at JAX, an Agilent 6530A QTOF purchased eight years ago, has severe limitations. The capacity of this aging instrument is severely limited, and investigators have encountered a number of challenges to outsourcing, including cost and availability. Together these represent a significant roadblock to research across JAX campuses, as mass spectrometry-based `omics techniques are proving critical to many investigators. The ThermoFisher Scientific Orbitrap Fusion Lumos Tribrid Mass Spectrometer addresses a significant number of these limitations. This system has additional fragmentation capabilities, unique isobaric labeling analysis capabilities, among the highest levels of sensitivity and mass resolution, and is capable of performing the needed myriad of proteomics analyses. In addition, JAX provides access to this premier instrument through the Mass Spectrometry and Protein Chemistry Service to researchers at regional institutions lacking this technology. Availability of the Lumos will significantly increase the capacity of MSPC to ensure high-quality, cost-effective proteomics analyses for the research programs of JAX investigators and researchers at regional institutions.