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We develop tools that leverage the unique characteristics of glycans—sugars that decorate the surfaces of all cells—to deepen our understanding of cellular functioning and pathology.
The building blocks of life fall into four broad categories: polynucleotides, proteins, lipids, and glycans. Each of these exhibits a useful set of characteristics (with some overlap). DNA/RNA base pairing enables data storage, transport, and amplification. Strings of amino acids adopt exquisite three dimensional folds, creating pockets for catalysis and shapes that bind one another. Lipids self-organize into droplets which are the basis for cellular compartmentalization. What about glycans? Why is it that all cells studied to date, from archaea to neurons, synthesize complex glycans and use them to decorate their cell surfaces?
In humans, glycans are biosynthesized from 9 monomeric carbohydrate units, but are not done so based on sequence templates encoded in the genome. Rather, glycans are highly dynamic products of combinatorial enzymatic pathways that react nimbly to cell state and external stimuli. In addition, monosaccharide units are linked together in a multitude of branching arrangements, resulting in extraordinary structural heterogeneity, which is elaborated further by post-synthetic modifications.
We are interested in developing methods rooted in chemical biology, protein engineering, and microscopy that leverage the unique characteristics of glycans to uncover new facets of cell biology. As glycans exert their key influence at cellular interfaces, we aim our technologies at the study of multicellular systems, and are especially curious about the roles glycans play in modulating ultrastructure and signaling in the brain. For example, we and others have observed microheterogeneity in the distributions of glycans on cell surfaces— what is the precise organization of these structured, densely-glycosylated cell surface domains and how do they influence neuronal/glial function? How does the tissue-level distribution of glycans in the brain influence communication among cell populations? How are these processes regulated over the course of development?