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: 1312646
• 负责人: Xiaoyang Zhu
• 金额: $ 30万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1312646&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.

该奖项由化学学部生命过程化学项目颁发。来自德克萨斯大学奥斯汀分校的朱晓阳和刘洪文将开发一种基于流体聚糖微阵列的新方法，在定量水平上对聚糖结合蛋白（GBP）的结合亲和力和特异性进行大规模分析，并指导合成具有增强亲和力和选择性的低聚糖结构。聚糖对所有生物体都是必不可少的，聚糖-蛋白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GBPs的复杂结合特异性是糖组学的主要目标之一。博士使用的流体聚糖微阵列。Zhu和Liu提供了两个关键优势：(1)它允许在多个数量级上精确控制聚糖密度，从而能够确定结合中的一个数据点（这在当前的聚糖微阵列技术中很常见），而是具有多价性和多价结合常数定量信息的完整结合等温线；(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，可以模拟复杂寡聚糖介导与GBPs结合的功能，从而为有针对性地设计和合成更复杂的低聚糖提供指导。该研究的长期目标是开发一种有效的糖组学定量工具，以了解和分析GBPs的特异性和选择性。该研究项目旨在从根本上了解活生物体中的细胞如何与其环境相互作用，更具体地说，了解甲型流感病毒如何攻击人体。甲型流感病毒亚型在历史上曾引起大流行，并由于禽流感和猪流感病毒的不断演变而构成严重危险。最近在禽类种群中暴发的H5N1毒株以及受感染人群的高致死率（60%）突出了这一关切。如果这些动物毒株获得特定的基因突变，从而能够在人与人之间传播，就可能导致大流行。了解甲型流感病毒的靶向特异性不仅对监测这类威胁很重要，而且对开发疫苗和治疗方法也很重要。除了基础科学，dr。朱和刘还将与一家高科技公司MicroSurfaces， Inc.合作，将学术研究转化为商业世界，并开发用于生化研究的新工具。