This proposal requests $600,000 towards the purchase of an orbitrap fusion tribrid HPLC- mass spectrometer to be put to work in the Proteomics Facility at the University of Maryland. A consortium of interest centers across the campus will provide the $262,077 match required to meet the full price of the system. Four major and eight minor users describe research projects that will benefit significantly from access to the sensitivity, cycle time and efficient ion activation of the state-of-the-art system. An experienced Facility Director and responsible management and financial plans are described. Ninety per cent of the instrument time is allocated to NIH-supported research. Many of the projects address critical changes that occur in proteins in both pathogens and host organisms during and resulting from infection. The new mass spectrometer will also advance understanding of the mechanisms by which ubiquitin conjugation controls the fate of many proteins in healthy and diseased cells.