Analytical and Biophysical Research Core

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Project Summary/Abstract The University of Mississippi proposes to establish the Glycoscience Center of Research Excellence (GlyCORE), a Phase I Center of Biomedical Research Excellence. Glycoscience is an essential and rapidly emerging field of biomedical science, and the challenging nature of glycoscience research requires tools and expertise that are not commonly found in the biomedical research community. Moreover, the biomedical community is rapidly growing to appreciate the essential role of carbohydrates, with researchers outside of the self-identified “glycoscience” community finding themselves faced with addressing challenging questions in glycoscience as part of the course of their biomedical researchers. The focus of the Analytical and Biophysical Research Core is three-fold: to train investigators new to glycoscience in proper carbohydrate sample preparation and handling; to support hypothesis-driven research with targeted quantitative analyses from both enriched samples and complex mixtures; and to support discovery-based research to give investigators a system-level view of changes upon perturbation of targeted systems. Training of researchers is a key function of the Core, especially in Phase I when the institutional level of expertise in glycoscience is in its earliest stage of development. Core 1 will train researchers in carbohydrate and carbohydrate conjugate sample preparation techniques. Targeted analyses will be provided as a key technology for hypothesis-driven research, where an investigator wants to test for the presence and quantity of a given glycan or glycoside, structurally characterize an unknown molecule, or validate a key biological or chemical resource. Structural analyses of glycan modification, protein-carbohydrate interactions, binding affinity estimations, and other biophysical analyses will be supported through MS-, LC- and spectrophotometry-based technologies. Access to NMR instrumentation and expertise in spectral acquisition and interpretation will also be provided. Finally, Core 1 will offer “omics”-style discovery-based surveys of glycomes, proteomes, metabolomes, etc. in quantitative, semi-quantitative, and qualitative fashions, supporting systems glycobiology and hypothesis development for targeted assay design. Core 1 will interface closely with the Computational Chemistry and Bioinformatics Core to provide advanced statistical and pathway analyses for “omics” data. The services of Core 1 will use both existing University of Mississippi resources as well as a dedicated high resolution Thermo Q-Exactive Plus LC-MS/MS system and a Dionex Ultimate 3000 analytical UHPLC system. Due to the poor UV-absorption characteristics of most carbohydrates, fluorescence detection for tagged carbohydrates and charged aerosol detection of underivatized carbohydrates will also be available for sensitive detection and quantitation at high dynamic range. By focusing our Phase I Analytical and Biophysical Core on a small number of flexible technologies, we can support the diverse glycoscience interests of UM investigators with cutting-edge technology using a limited array of equipment and have room for growth as GlyCORE matures.