Date/Time
Date(s) - 20/03/2025
1:30 pm - 2:20 pm

Title: Chemical Tools to Study Cellular Carbohydrates

Date: Thursday March 20, 2025

Time: 1:30-2:20pm

Room: ABB 165

Host: Dr. Alex Adronov

Abstract: 
Carbohydrates are ubiquitous and drive essential biological processes. Understanding molecular determinants of these important functions is critical for both fundamental and translational research. This lecture will cover two stories, with the first focusing on the development of chemical tools to study bacterial glycans and second centering on application of chemical tools to answer fundamental questions in human biology. Methods for probing glycan structure and function remain limited as these structures are incompatible with common strategies used to study other biomacromolecules. Unlike the amino acid residues that constitute proteins, which contain a wide array of distinct reactive groups, glycan building blocks are composed primarily of polyol isomers and lack distinguishing reactivity required for selective labeling. To address this challenge, we developed novel chemical tools to study bacterial cell surface glycans. Our method relies on the direct incorporation of reactive glycan building block surrogates by cell surface glycosyltransferases, a technique termed “biosynthetic incorporation.” Using this technique, we have established a generalizable strategy for chemoselective glycan modification, enabling the study of specific bacterial cell wall glycans. The second part of the lecture will focus on applying chemical tools to address an outstanding question in glycobiology: what are the most essential functions of the multifunctional enzyme O-linked N-acetylglucosamine transferase (OGT) in human cells? The diverse catalytic and non-catalytic activities facilitated by this single enzyme make it unique and have inspired years of research into how these functions are coordinated in a cell. Despite almost four decades of study, many aspects of OGT’s cellular functions remain unknown. We have tackled this question by harnessing chemical tools to inhibit catalytic function or complete degrade OGT, deconvoluting the cellular vulnerabilities associated with its catalytic and non-catalytic functions in a genome-wide chemical genetic screen. Hits from this screen will be useful new drug targets and will provide new information about OGT biology. As a whole, this lecture will cover the development and application of chemical tools in the field of glycobiology.

Biography:
Victoria is a Postdoctoral Fellow in the Professor Suzanne Walker’s lab, in the Department of Microbiology at Harvard Medical School. Victoria received her BSc in Chemical Biology at McMaster University doing research as an undergraduate in Professor Alex Adronov’s lab. As an undergraduate she participated in the co-op program spending time at the Karolinska Institute in Stockholm, Sweden and a CRO called NMX Research and Solutions in Montreal. She then completed her PhD in Chemistry at Massachusetts Institute of Technology under the supervision of Professor Laura Kiessling, supported by an NSERC PGS-D fellowship. As a graduate student, she developed chemical tools to study bacterial cell surface glycans. As a Postdoctoral Fellow she currently uses chemical and biochemical tools to investigate mammalian and bacterial glycobiology.