Dynamic Self-Assembly of Glycolipids for Unveiling Complex Glycan-Protein Interactions

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In this award from the Chemistry of Life Processes Program in the Division of Chemistry, Drs. Xiaoyang Zhu and Hung-Wen Liu, from the University of Texas at Austin, will develop a novel approach based on fluidic glycan microarrays to carry out large-scale analysis of glycan binding proteins (GBP) binding affinity and specificity at a quantitative level, and to guide the synthesis of oligoglycan structures with enhanced affinity and selectivity. Glycans are essential to all living organisms and glycan-protein interaction determines a wide range of cell surface processes, such as pathogen recognition, cell-cell communication, and the innate immune response. Mapping and understanding the complex binding specificities of GBPs is one of the major goals of glycomics. The fluidic glycan microarray used by Drs. Zhu and Liu offers two critical advantages: (1) it allows precise control of glycan density over many orders of magnitude, enabling the determination of not one data point in binding (as is common in current glycan microarray technology) but rather a complete binding isotherm with quantitative information on multivalency and the multivalent binding constant; and (2) the dynamic assembly of simple glycans in the fluidic lipid bilayer environment, combined with the flexibility of glycan structures, may allow the functional simulation of complex oligoglycans in mediating binding to GBPs, thus providing guidance in the targeted design and synthesis of more complex oligoglycans. The long-term objective of the proposed research is to develop an effective and quantitative tool in glycomics for the understanding and analysis of the specificity and selectivity of GBPs.This research project seeks fundamental understanding of how cells in living organisms interact with their environment and, more specifically, how influenza A viruses attack the human body. Subtypes of influenza A virus have caused pandemics throughout history and pose grave danger due to the continuous evolution of avian and swine viruses. This concern is underscored by recent outbreaks of the H5N1 strain among avian population and the high fatality rate (60%) in infected human population. Should such animal strains acquire particular genetic mutations to allow human-to-human transmission, pandemics could result. Understanding the targeting specificity of influenza A virus is important not only for the surveillance of such threats but also for the development of vaccines and treatments. In addition to fundamental science, Drs. Zhu and Liu will also collaborate with a high-tech company, MicroSurfaces, Inc., in translating academic research to the commercial world and in developing new tools for biochemical research.