Orbitrap Astral for Wayne State Proteomics - Project Summary/Abstract The goal of this proposal is to bring a Thermo Fisher Scientific Orbitrap Astral mass spectrometer with a High-Field Asymmetric Waveform Ion Mobility Spectrometry (FAIMS Pro Duo) devise, an Ardia Instrument Control and Data Management system plus a nano-LC to the Proteomics Core at Wayne State University. The Proteomics Core supports an extensive user base including 7 Major Users and 19 Minor Users who have contributed to the proposal and who have NIH-funded projects that will be advanced by having access to the Orbitrap Astral. The Proteomics Core at Wayne State also supports the Karmanos Cancer Institute and the P30 funded Cancer Center as well as the NIEHS funded CURES P30 Center and CLEAR P42 Superfund Center. This Orbitrap Astral has unique capabilities for deep profiling of complex proteomes using Data Independent Analysis (DIA) acquisition. Advances in the Orbi Astral that make it unique for DIA are the 200 Hz scan speed with 80,000 Resolution and superior sensitivity. These features allow the Astral to acquire DIA data using 2 Da windows, something no other MS system can achieve. The new mass analyzer in the Orbitrap Astral make it an exceptional instrument for DIA proteomics. Combined with the experienced mass spectrometrists in the Core, the Orbitrap Astral will be a major asset to research programs of NIH-funded investigators at WSU and in the SE Michigan region. As investigator needs have evolved they have developed an increased need for higher resolution, greater sensitivity and higher mass accuracy proteomic mass spectrometry. The Orbitrap Astral is designed to address todays needs in proteomic analysis. The instrument excels at deep sequencing and quantitative proteomics as well as accurate characterization of post translational modifications. The current mass spectrometers in the Core lack fast duty cycles and the advanced ion optics that make detection of low abundance species routine on the Astral. The ability to unambiguously localize post translational modifications (PTM) in peptides is a critical feature in any proteomic MS system and the Astral is outstanding in this due to the high degree of coverage within the identified proteins. Wayne State University is strongly committed to this proposal as evidenced by a combined $350,000 in new support for the instruments management, operation, maintenance, informatics and usage. The technical expertise of Proteomics Core personnel as well as the physical and administrative infrastructures are all in place and ready to immediately put this new mass spectrometer to work on NIH-funded biomedical research projects. This instrument will provide transformative technologies for advancing dozens of NIH- funded, ongoing projects, as well as catalyzing new research directions for investigators at Wayne State University.