Aquisition of a Orbitrap IQ-X Mass Spectrometer System with Vanquish Flex UHPLC System for Nucleic Acid Adductomics

PROJECT SUMMARY Funds are requested to purchase a Thermo Fisher Scientific Orbitrap IQ-X Mass Spectrometer System with Vanquish Flex UHPLC System (IQ-X) to establish a unique omics capability at the University of South Florida (USF), with analytical performance that is not currently available as a shared resource, for detailed, high-resolution structural analysis of low-level small molecules in

complex biological matrices. Specifically, we have developed Nucleic Acid Adductomics (NAA) which aims to describe the totality of modifications in the genome i.e., DNA, and RNA products plus other significant classes of adducts e.g., DNA-DNA, RNA-RNA, DNA-protein, and RNA- protein crosslinks, all of which are implicated in pathogenesis. The requested instrument will be

the only one of its kind outside of Taiwan performing NAA, and will support efforts to better understand the role of NA modifications in health and disease. Over twelve NIH-funded principal investigators (major users, representing 24 awards) across USF/Moffitt Comprehensive Cancer Center need the analytical capabilities provided by the IQ-X. Specifically, they need to identify the

diverse range of NA modification types, and an unprecedented number of individual adducts, through ultra-high mass measurement accuracy and resolution, and unique scanning features (e.g., neutral loss-driven MS2 or MSn analysis for structure elucidation), while maintaining a respectable sample analysis time. An accompanying need is to perform targeted adductomics for

specific nucleic acid-derived biomarkers in complex matrices with significant chemical noise. For analytical and user convenience, the instrument will be housed within the Proteomics Facility located in the Florida Center for Excellence for Drug Discovery and Innovation, at USF. The instrument will support NIH-funded investigators from multiple departments across major USF

colleges (e.g., Arts and Sciences, Medicine, Public Health) and Moffitt. The IQ-X will be the first instrument of its kind at USF, and will be dedicated to performing non-targeted and targeted NAA, with options to focus on cellular, nuclear, or mitochondrial targets, and extracellular matrices, such

as urine. The instrument will be used to enhance basic and translational, NIH-funded research programs at USF/Moffitt that cover a wide range of topics e.g., infectious disease, genome instability, carcinogenesis, respiratory, cardiovascular, and neurological disorders. This cutting- edge technology will accelerate new and important discoveries for multiple projects, as well as

opening new directions of research in the biomedical sciences, and improving our understanding of the mechanisms underlying pathogenesis.