Abstract: Carbohydrates are incredibly diverse biomolecules that facilitate communication between cells and between organisms. Nevertheless, much remains unknown about the exact molecular determinants and mechanisms of these glycan-mediated processes. In this talk, I will use two examples to illustrate how the development and utilization of chemical methods can broadly improve our understanding of carbohydrate function. First, I will highlight how tools to detect glycan-protein interactions, validate binding sites, and generate precise animal models were used to uncover polysaccharide ligands for a mammalian orphan receptor that regulates vascular physiology. Second, I will describe how an enzyme-centric workflow using biochemical characterization and in vivo phenotyping revealed new sources of bioactive glycopeptides from the gut microbiota to improve cancer immunotherapies. Together, these examples will underscore how integrated approaches rapidly enable structure-function studies for mammalian and microbial carbohydrates and provide a discovery platform for novel glycan activities in health and disease

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