Project Abstract This is an application requesting funds to purchase a Bruker timsTOF HT mass spectrometer and NanoElute 2 liquid chromatography system that will be used for proteomics research. The instrument will be integrated into the Robert Wood Johnson Medical School/Rutgers-New Brunswick Biological Mass Spectrometry Facility in Piscataway New Jersey. We current operate two mass spectrometers, a Thermo Eclipse tribrid, which is used for the majority of our projects and an almost 10-year old Thermo QExactive HF. There are two justifications for our request. First, we need additional capacity. The Eclipse is used at maximal capacity thus we require additional an instrument to meet the demands of our NIH-funded investigators. In addition, we have no substitute for the Eclipse when the instrument in inoperable - the QExactive, which is close to the end of its functional lifespan, cannot replace the Eclipse for most projects. Second, we need additional capabilities. The proteomics field is increasingly turning towards label-free, data-independent acquisition (DIA) methods for proteome-wide quantitative mass spectrometry. Our Eclipse is an excellent instrument in many respects but our comparison studies clearly indicate that the Eclipse is inferior to the Bruker timsTOF in terms of proteome coverage, number of peptides assigned and accuracy of quantitation. This instrument will greatly enhance the ability of NIH-funded scientists on the Piscataway and New Brunswick campuses of Rutgers University to conduct cutting-edge biomedical research and it will also provide access to cutting-edge technology for the many new junior Faculty recruits at Rutgers. Availability of this technology will allow our User group to better address a wide range of specific diseases including asthma and respiratory disease, neurological disease, bacterial and viral infection, disruption of endocrine function, skin disorders, sleep disorders, diabetes, digestive disease, inflammation and cancer, as well as other fundamental issues of biomedical importance. The requested instrument will represent a significant asset to our research community and will accelerate the pace of basic and applied biomedical research of NIH-funded investigators on the New Brunswick and Piscataway campuses of Rutgers, the State University of New Jersey.