This S10 Shared Instrumentation Grant for a SCIEX ZenoTOF 7600 microflow LC-MS system represents a significant upgrade in the capabilities of the mass spectrometer (13-year-old SCIEX TripleTOF 5600) currently used for metabolomics and lipidomics at the University of Alabama at Birmingham. It will aid investigators by adding the ability to perform tunable electron activation dissociation (EAD) as well as much increased sensitivity for classical collisional activation dissociation (CID) provided by an ion trap within the collision cell. EAD will result in enriched product ion spectra for lipids and other metabolites. The increased sensitivity and dynamic range will greatly assist and improve the analysis of metabolomes of all applications, in particular, to small animal models such as the fruit fly. The instrument will support the research of 16 NIH- funded investigator teams (8 major user teams and 8 minor user teams) who have current year NIH direct cost funding totaling $5.85 million. Their research covers a wide range of areas relevant to the health of Americans: these include aging, Alzheimer disease, cancer therapy and prevention, cardiac and cardiovascular disease, cytomegaloviral infection and other infectious diseases, lung disease, precision medicine, and psychostimulant abuse. The choice of the instrument to pursue this research is part of an ongoing review by an Oversight Committee consisting of two experienced investigators who are not named users, a major and a minor named user, a Center Director (Chair of the Committee and a previous user), the Director of the Precision Medicine Institute and a former Department Chair and the 2023 President of FASEB (non-user); a business officer (non-voting) will provide financial advice to the committee. This Committee will also provide overview and advice on the operation of the selected instrument, including recommendations regarding the price structure for the use of the instrument and plans for future funding to maintain the instrument. Training in the use of the instrument will be conducted on a one-on-one basis with students and postdoctoral fellows of the NIH-supported investigators by an experienced operator, Mr. Wilson. The PI, Dr. Barnes, will provide advice to investigators on how to design projects for MS-based analysis. He will coordinate with Dr. Gaggar regarding sample acquisition from clinical and translational models. Dr. Prasain will provide expert advice on de novo interpretation of MSMS spectra. Training in metabolomics data will be provided to investigators, graduate students and postdocs through existing courses and 1-day and 1-week workshops supported by the UAB Center for Clinical and Translational Science.

The addition of a SCIEX ZenoTOF 7600 microflow LC-MS system with tunable electron activation disassociation and much enhanced sensitivity will significantly enhance the funded research of 16 UAB investigators. Their research is being applied to many of the major health issues facing Americans – aging, Alzheimer disease, cancer prevention and therapy, cardiac and cardiovascular disease, cytomegaloviral infection and other infectious diseases, lung disease, precision medicine for childhood genetic disease, and psychostimulant abuse.