Vanquish Neo UHPLC for The Wertheim UF Scripps Institute - PROJECT SUMMARY/ABSTACT This proposal seeks funds to purchase a Thermo Scientific Vanquish Neo UHPLC for upfront peptide separation prior to mass spectrometric analysis for The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology in Jupiter, Fl. The system will be placed in the Mass Spectrometry and Proteomics Core and coupled to an Orbitrap Fusion Tribrid mass spectrometer. The instrument will serve two primary purposes: 1) replacement of the old EASY-nLC 1000 HPLC from Thermo Scientific which will no longer be serviceable past February 2024 (product line is being retired end of 2023), and 2) sustain bottom-up proteomics services and experimentation for over 30 investigators of the institute and neighboring and national institutions, annually. Four major users from The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, the University of Miami, and Seattle Children's Research Institute, with 17 active NIH-funded grants, have been identified with current and future research projects, which ensures immediate and long-term continued use of this instrument. There are also 7 additional minor users. The group of major users will utilize the instrument for peptide separations in front of Orbitrap-based mass spectrometry bottom-up proteomic analyses. The specific research projects of the major users that will require bottom-up proteomics vary but will globally address problems related to neurodegenerative and neuropsychiatric diseases, drug abuse, and HIV infection and treatment. The Vanquish Neo UHPLC is a new liquid chromatography system by Thermo Scientific that provides all-in- one nano-, capillary- and micro-flows compatible with high sensitivity LC-MS workflows, reproducible peptide separations, and ease of use. It is also importantly serviceable as a bundled system with the Orbitrap Fusion Tribrid mass spectrometer which is also manufactured by Thermo Scientific. As such it is well suited to sustain current Orbitrap-based bottom up services (qualitative and quantitative proteome investigations). The Vanquish Neo UHPLC instrument will be housed in the Mass Spectrometry and Proteomics Core facility, a central mass spectrometry shared resource at The Herbert Wertheim UF Scripps Institute in Jupiter, FL (formerly Scripps Research FL/The Scripps Research Institute). The Core is administered by the Institution, within a well- structured Core framework of 11 other Facilities, and includes Oversight and Advisory committees. There is very strong financial support from the local Institution and the University of Florida to ensure long-term utilization of the instrument. This includes financial support for service agreements for the next 5 years and salary support of a full-time Ph.D. mass spectrometrist to operate the instrument (Scientific Core Director) and a Research Assistant II staff scientist. The long-term impact to The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology and regional institutions will be the addition of a new HPLC that will sustain LC-MS resources for the scientific and medical research community, and the next generation of scientists.