Glycosylation is one of the most frequent post-translational modifications. Interest in the biological roles of lipid and protein glycosylation has intensified because of increasing examples of their importance as recognition determinants. It has been estimated that about 0.5-1.0% of the translated mammalian genome participates in oligosaccharide production and function and many specific roles have now been documented to involve glycan structures. Four areas of research that have received considerable attention are (i) development and differentiation, (ii) cell adhesion and inflammation, (iii) cancer and metastasis, and (iv) host-pathogen interactions in infection diseases.
The biosynthesis of glycans is catalyzed by glycosyltransferases, a family of 100 or more enzymes which transfer a sugar residue from a nucleotide-sugar donor to an acceptor which can be a sugar, an amino acid, or a lipid. These glycosyltransferases are classified on the basis of the carbohydrate residue they transfer, (e.g., galactosyltransferases, sialyltransferases, fucosyltransferases), and are distinguished by the sugar they recognize as an acceptor. Two fundamental features make structural characterization of these materials extremely difficult: product structures are frequently branched with considerable isomerism, and individual moieties are controlled at the level of transferase expression (not a direct product to be identified from the genome).
Work in our laboratory has focused strongly on methods development in past years and more recently on application of these strategies and techniques to relate carbohydrate detailed structure to function. For reasons of sensitivity and specificity these methods depend heavily on mass spectrometry and their adjunct techniques. Latest studies have involved the use of ion trapping to determine carbohydrate structures where specific ions are selected for activation, collision, and measurement multiple times, MSn. This ability to isolate substructures for further characterization has become of vital importance to understand the detailed linkage and branching patterns inherent in lipid and protein glycosylation.
Ph.D., Biochemistry, University of Vermont
M.S., Biochemistry, University of New Hampshire
B.S., Chemistry, University of New Hampshire
BCHM 999: Doctoral Research
INCO 590: Rsrch Exp/MCBS
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