Chemical Biology Tools for Probing and Discovering Glycan-Protein Interactions

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Cells of all living systems are surrounded by a "sugar coating" that is composed of carbohydrates covalently linked to proteins (called glycoproteins) or lipids (called glycolipids). The carbohydrates found on cell-surfaces, also called glycans, are crucial for normal physiology by mediating a range of important biological processes, and are also directly involved in every major disease. Through highly selective interactions with glycan-binding proteins, cell-surface glycans initiate or modulate specific functions in cells. While the importance of these interactions is well recognized, our current understanding of the glycan structures involved in these crucial binding events is limited. Indeed, research in carbohydrates and the glycosciences field significantly lags behind other biomolecules of life (proteins, lipids, nucleic acids). A major reason for this knowledge gap is that there is a limited availability of chemical tools to efficiently synthesize and study biologically relevant complex glycan structures. Our interdisciplinary research program will address these issues by developing innovative chemical biology tools and strategies that will be used to study and understand the mechanisms by which carbohydrates interact with proteins. This will be achieved through two main aims. We will develop efficient chemo-enzymatic strategies that will enable access to poorly understood, biologically relevant complex glycan structures that are needed to be able to study how these molecules interact with proteins. We will also develop new chemical tools to probe glycan-protein interactions, particularly in cell-based platforms as information on the cellular function of complex glycans is currently lacking. The resulting new chemical toolbox will benefit a broad range of researchers in the glycoscience field and will enable an improved understanding of how complex glycans interact with proteins and elicit functions in cells. Knowledge gained from this research program will allow us to answer fundamental questions at the interface of chemistry and biology in the rapidly progressing field of glycosciences. HQP trained in this program will be at the forefront of developing new chemical technologies that will progress the field into new directions and they will obtain a diverse interdisciplinary skill set with expertise in organic synthesis, biochemistry, molecular biology, enzymology, and chemical biology.