Keywords: O-GlcNAc, protein engineering, nanobody, signaling, glycoproteomicsenzymes, which makes the measurement of a functional contribution of O-GlcNAc on a specific target challenging. New strategies to edit O-GlcNAc on a target protein in cells are needed to facilitate elucidation of O-GlcNAc’s physiological function and eventual therapeutic interventions.In order to explore the role of O-GlcNAc on target proteins in human disease, we developed a cellular approach for writing and erasing O-GlcNAc from target proteins in the cell. The method uses a nanobody fused to an O-GlcNAc writer or eraser to control O-GlcNAc levels on the desired target protein. Nanobodies are small single-domain protein Special LectureOver 15% of the cellular proteome is modified by O-linked N-acetyl glucosamine (O-GlcNAc), a monosaccharide post-translational modification (PTM) that is attached to serine or threonine residues of nuclear, cytosolic and mitochondrial proteins. Due to the ubiquitous nature of the modification, O-GlcNAc has been implicated in numerous biological processes, including immune response, cancer progression, neurodegenerative disease, and diabetes. O-GlcNAc is regulated on its thousands of protein substrates by the action of a pair of enzymes, O-GlcNAc transferase (OGT) for installation and O-GlcNAcase (OGA) for removal of the modification. O-GlcNAc is dynamically added or removed from proteins by these two Christina M. Woo is an Associate Professor in the Department of Chemistry and Chemical Biology at Harvard University, and an affiliate member of the Broad Institute. She obtained a BA in Chemistry from Wellesley College (2008) and a PhD from Yale University (2013) as an NSF predoctoral fellow under the guidance of Professor Seth Herzon. Christina completed her postdoctoral studies with Professor Carolyn Bertozzi at the University of California Berkeley as a Jane Coffins Child postdoctoral fellow and at Stanford University (2015) as a Burroughs Wellcome Fund postdoctoral fellow, where she developed a mass-independent chemical glycoproteomics platform for mapping non-templated post-translational modifications. Christina joined the faculty at Harvard University in 2016. Research in the Woo Lab focuses on the design of chemical approaches to alter post-translational modifications and the signaling outcomes they produce in cells. Christina has received the David Gin Young Investigator Award, Camille-Dreyfus Teacher-Scholar Award, Sloan Research Foundation, NSF CAREER, Bayer Early Excellence in Science Award, the NIH DP1 Avenir Award, and the Ono Pharma Foundation Breakthrough Science Award.18Christina M. WooDepartment of Chemistry and Chemical Biology,Harvard University13:20-14:00Writing and erasing O-GlcNAc fromtarget proteins in the cell1
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