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National Center for Glycomics and Glycoproteomic

Milos V. Novotny, Ph.D.

Center Overview

The National Center for Glycomics and Glycoproteomics (NCGG) focuses on developing highly sensitive methodologies and new instrumental capabilities for glycomic and glycoproteomic analyses of complex biological systems. In collaboration with biological and biomedical investigators, conceptually important applications are being sought to emphasize the advantages of sensitive and accurate measurements as well as the structural information provided through bioinformatic tools in glycomics and glycoproteomics. The unique methodologies offered by the center include isotopically-coded glycan analysis by mass spectrometry (MS), high-energy collision-induced dissociation of permethylated glycans, photofragmentation MS, lectin fractionation of complex glycoprotein mixtures, microchip-based glycobiology, and tandem ion mobility spectrometry. The emphasis has been focused on interfacing microcolumn separations with the state-of-the-art MS in integrated analytical platforms to maximize analytical capabilities.

Current Research

In the area of glycomic measurements, the center has recently developed quantitative tools for conversion of various glycans to their fully methylated derivatives at nanoscale. This permits highly informative tandem MS identification and glycan profiling from complex glycoprotein mixtures and various biological materials. Using the isotopically-aided labeling, it has become possible to investigate aberrant glycosylation in diseases such as cancer and alcoholism. In the area of glycoproteomics, it has utilized unique preconcentration procedures (based on the lectin-glycoconjugate interactions) to profile complex glycoprotein/glycopeptide mixtures from minute quantities of tissue extracts and physiological fluids. The new analytical platforms are oriented toward finding disease biomarkers. Besides developing new chemical approaches to glycoconjugate analysis, our strong emphasis has been on designing new instruments and analytical capabilities. Current activities include sophisticated instrumentation of tandem ion-mobility spectrometry (IMS-IMS and IMS-IMS-IMS), photofragmentation MS and multiplexing MS techniques as well as microfluidic sample treatment and separations. The center's strong emphasis has been the optimum utilization of separation methodologies in conjunction with MS techniques and computer-aided bioinformatics. The newly developed tools are being tested through unique biomedical applications.