Novel Tools for Glycobiology - Integrating Chemical and Genetic Approaches

When bacteria attack the human body, the first contact is often made through little antennae on the surface of the invader. Similar antennae are also used by cancer cells when they spread within the body, and by cells of the immune system when an inflammatory reaction spins out of control. Whatever the nature of the individual organism or cell, these antennae are, perhaps surprisingly, made of molecular building blocks very similar in structure to the molecules ordinary sugar is made of. However, the antennae found on bacteria and cancer cells are much more complex than ordinary sugar. A complex machinery, a group of enzymes called glycosyltransferases, inside the bacteria and cancer cells is required to put them together. In our research, we use a combination of chemistry and molecular biology to take apart the glycosyltransferase machinery and understand the role of the individual parts. Ultimately, a better understanding of the glycosyltransferase machinery will give us a handle on treating infections and cancers more efficiently.

Glycosyltransferases are important biosynthetic enzymes involved in many biological processes underpinning human health and disease, including carcinogenesis, inflammation and infection. At present, our understanding of this large and complex enzyme family (20,000+ members) remains fragmented. In this project, a combination of chemical and genetic approaches will be used to advance research into therapeutically relevant glycosyltransferases. A general glycosyltransferase assay will be established to facilitate the discovery of novel, therapeutically interesting glycosyltransferase inhibitors. In addition, complementary pairs of donor analogues and glycosyltransferase mutants will be generated for the in vivo investigation of individual glycosyltransferases in complex glycosylation networks.