Harnessing Chemistry to Understand the Sweeter Side of Cell Signaling

November 10, 2017

Dr. Linda Hsieh-Wilson, Division of Chemistry and Chemical Engineering, California Institute of Technology

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The field of chemical neurobiology is rapidly evolving and providing insights into the molecules and interactions involved in neuronal development, sensory perception and memory storage. We are interested in understanding how specific carbohydrate structures contribute to the formation and strengthening of neural connections.  Chondroitin sulfate glycosaminoglycans are extracellular polysaccharides that participate in brain development and spinal cord injury.  We have developed chemical strategies to elucidate the structure-activity relationships of chondroitin sulfate and discovered that these molecules participate as ligands in signaling events that underlie processes such as axon regeneration and the formation of neural circuits.

 In the intracellular context, the covalent attachment of O-linked-b-N-acetylglucosamine (O-GlcNAc) to protein side chains is a dynamic posttranslational modification that shares features with protein phosphorylation. We have developed chemoenzymatic strategies to detect and study O-GlcNA glycosylation and its roles in the regulation of gene expression and cancer cell metabolism. We are also developing a new systems-level approach for studying the function, specificity and regulation of O-GlcNAc glycosylation.  Elucidation of the dynamic cellular networks of O-GlcNAc glycosylation provides insights into its central functions and may reveal new approaches to selectively modulate it.

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