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

糖脂的动态自组装揭示复杂的聚糖-蛋白质相互作用

• 批准号: 1152772
• 负责人: Xiaoyang Zhu
• 金额: $ 30万
• 依托单位: University of Texas at Austin
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2013-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1152772&HistoricalAwards=false
• 关键词: Dynamic; Self; Assembly; Glycolipids; Unveiling

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.

在化学过程中的化学过程中，化学系的奖项中，博士。来自德克萨斯大学奥斯汀分校的肖阳和洪刘将基于流动性聚糖微阵列开发一种新颖的方法，以对聚糖结合蛋白（GBP）结合亲和力和特异性进行大规模分析，并以定量的水平进行特异性，并指导具有增强亲和力和选择性的寡头结构的合成。聚糖对于所有生物体都是必不可少的，而聚糖 - 蛋白质相互作用决定了广泛的细胞表面过程，例如病原体识别，细胞 - 细胞通信和先天的免疫反应。映射和理解Gbps的复杂结合特异性是糖基质的主要目标之一。 DRS使用的流体聚糖微阵列。朱和刘提供了两个关键优势：（1）它允许在许多数量级上精确控制聚糖密度，从而确定绑定中没有一个数据点（在当前的Glycan微阵列技术中很常见），而是具有多价值和多价结合常数的定量信息的完整绑定等等距； （2）流体脂质双层环境中简单聚糖的动态组装，结合聚糖结构的灵活性，可以允许对复杂的寡聚结合的功能模拟，从而介导与Gbps的结合，从而在靶向设计和更复杂的寡糖合成中提供指导。拟议研究的长期目标是开发一种有效的定量工具，以理解和分析GBP的特异性和选择性。本研究项目寻求对生物体中的细胞如何与环境相互作用，更具体地，更具体地，更具体地说，是对人体攻击人体的影响。流感病毒的亚型在整个历史中引起了大流行病，并由于鸟类和猪病毒的不断发展而构成了严重的危险。最近在鸟类人群中H5N1菌株的爆发以及感染人群的高死亡率（60％）引起了人们的关注。如果这种动物菌株获得特定的基因突变以允许人类到人类传播，则可能会导致大流行。了解流感病毒的靶向特异性不仅对于监视此类威胁，而且对于开发疫苗和治疗而言很重要。除了基本科学，博士。朱和刘还将与高科技公司Microsurfaces，Inc。合作，将学术研究转化为商业世界，并开发新的生化研究工具。