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

在化学系生命过程化学项目的这一奖项中，德克萨斯大学奥斯汀分校的朱晓阳博士和刘洪文博士将开发一种基于流体聚糖微阵列的新方法，以定量水平对聚糖结合蛋白（GBP）结合亲和力和特异性进行大规模分析，并以增强的亲和力和选择性指导寡聚糖结构的合成。聚糖对所有生物体都是必不可少的，聚糖-蛋白质相互作用决定了广泛的细胞表面过程，如病原体识别，细胞间通讯和先天免疫反应。绘制和理解GBP的复杂结合特异性是糖组学的主要目标之一。Zhu和Liu博士使用的流体聚糖微阵列提供了两个关键优势：（1）它允许精确控制聚糖密度超过许多数量级，从而能够确定结合中的非一个数据点（如在当前聚糖微阵列技术中常见的）而是具有关于多价性和多价结合常数的定量信息的完整结合等温线;以及（2）简单聚糖在流体脂质双层环境中的动态组装，结合聚糖结构的灵活性，可以允许在介导与GBP的结合中功能模拟复杂的寡聚糖，从而为更复杂的寡聚糖的靶向设计和合成提供指导。建议研究的长远目标是发展一种有效的糖组学定量工具，以了解和分析GBP的特异性和选择性。这项研究项目旨在从根本上了解生物体中的细胞如何与其环境相互作用，更具体地说，甲型流感病毒如何攻击人体。甲型流感病毒的亚型在历史上引起了大流行，并由于禽流感病毒和猪流感病毒的不断进化而构成严重危险。最近H5 N1毒株在禽类中的爆发以及受感染人群的高死亡率（60%）突出了这一关切。如果这些动物菌株获得特定的基因突变，使人与人之间的传播，大流行病可能会导致。了解甲型流感病毒的靶向特异性不仅对监测此类威胁很重要，而且对疫苗和治疗方法的开发也很重要。除了基础科学，朱博士和刘博士还将与高科技公司MicroSurfaces，Inc.合作，在将学术研究转化为商业世界和开发生物化学研究的新工具方面。

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.