Studies of the O-GlcNAc Modification

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The sequencing of the human genome revealed a frightening observation. On the face of it, humans are not very complex at all: only 20-25,000 genes. Yet, as we all know, humans ARE complex organisms. This complexity is derived, in part, from chemical events that take place withing our cells which serves to expand the complexity of proteins - the products of these these 20,000 genes. One of the most important modifications that can take place withing cells is glycosylation of proteins with a sugar called N-acetylglucosamine. This is a dynamic modification: sugars can be put on and taken off in response to diverse stimuli including diet, hormones etc. These modifications are also very important in that it controls the function of the healthy cell. Furthermore, aberent states of modifications are linked to diseases such as cancer, and diabetes. The research proposed in this grant seeks to understand the chemistry and biochemistry of this N-acetylglucosamine modification. This will allow researchers to probe the biology of the healthy cell and also allow the design and exploitation of chemical molecules to inform our knowledge of disease processes.