A new tool for the analysis of glycan recognition by lectin

有了这个奖项，化学部的生命过程化学计划正在资助来自德克萨斯A M大学的Hung-Jen Wu和Joseph Kwon博士开发下一代糖阵列工具，该工具可用于研究聚糖和凝集素之间的复杂相互作用，这两者都是生命系统中发现的生物分子。更具体地，凝集素是识别和结合聚糖的蛋白质，聚糖是碳水化合物分子;凝集素和聚糖之间的结合在广泛的生理和病理过程中起重要作用。凝集素-聚糖结合具有几个重要特征。 首先，它不是高度特异性的;凝集素通常以不同的亲和力与不同的聚糖结构结合。大多数凝集素通过多价相互作用与聚糖结合，即单个凝集素的多个结合结构域同时与多个聚糖分子相互作用。此外，附着于脂质或膜蛋白的聚糖可以在二维细胞膜上扩散。这些特征将凝集素-聚糖相互作用与经典的双分子相互作用（例如抗体和抗原之间的那些）区分开。现有的凝集素分析方法错过了这些基本特征，因此往往无法描述糖生物学中的一些意想不到的现象。该研究项目的目标是建立下一代糖阵列工具，以满足这一关键需求，并使发现凝集素-聚糖识别原理成为可能。该项目还涉及开发一个基于项目的学习计划，重点是支持高中学生学习化学和纳米科学主题。学生参与者从事动手实验和互动活动。Wu博士和Kwon博士的团队正在将该教育项目转变为面向教师的开放式网络课程，目的是提高他们的STEM推广工作的影响力。Wu博士和Kwon博士正在开发一种高通量纳米立方体传感器阵列，以定量测量模拟细胞膜环境中的凝集素-聚糖相互作用。此外，正在开发一种动力学蒙特卡罗模拟，用于模拟复杂的凝集素-聚糖相互作用。这种新型的糖阵列工具，集成了分析测定和计算建模允许一个测量基本的微观结合参数，这反过来又可以用于预测凝集素功能的复杂细胞表面。该工具使得同时检查半特异性、多价性和配体扩散对凝集素-聚糖识别的影响成为可能。凝集素-聚糖识别模式的分析变得非常容易、灵活和便宜。最终用户可以在自己的实验室中进行测量，而无需专门的设备，只需遵循复杂建模软件中包含的分步指南。该检测工具与多种聚糖结合物种兼容，包括毒素、细菌、病毒和癌细胞;因此，它可以使广泛的科学界受益。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Drs. Hung-Jen Wu and Joseph Kwon from Texas A&M University to develop a next-generation glycoarray tool that can be used in the study of the complex interactions between glycans and lectins, both of which are biomolecules found in living systems. More specifically, lectins are proteins that recognize and bind glycans, which are carbohydrate molecules; the binding between lectins and glycans plays an important role in a wide range of physiological and pathological processes. Lectin-glycan binding has several important features. Firstly, it is not highly specific; a lectin often binds to different glycan structures with different affinities. Most lectins bind to glycans via multivalent interactions, i.e. multiple binding domains of a single lectin simultaneously interact with multiple glycan molecules. Moreover, glycans attached to lipids or membrane proteins can diffuse on two-dimensional cell membranes. These features distinguish the lectin-glycan interactions from classic bimolecular interactions such as those between antibodies and antigens. Existing methods for lectin analysis miss these essential characteristics, and thus often fail to describe some unexpected phenomena in glycobiology. The goal of this research project is to establish a next-generation glycoarray tool that fills this critical need and makes possible the discovery of the lectin-glycan recognition principles. The project also involves the development of a project-based learning program that focuses on supporting the learning by high school students of chemistry and nanoscience topics. The students participants are engaged in hands-on experiments and interactive activities. Drs. Wu and Kwon's team is converting the educational program to an open-access web-based course for teachers with the goal of increasing the impact of their STEM outreach efforts.Drs. Wu and Kwon are developing a high-throughput nanocube sensor array to quantitatively measure lectin-glycan interactions in an environment that mimics the cell membrane. In addition, a kinetic Monte Carlo simulation is being developed for modeling complex lectin-glycan interactions. This novel glycoarray tool that integrates analytical assay and computational modeling allows one to measure fundamental microscopic binding parameters, which in turn can be used in the prediction of lectin functions on complex cellular surfaces. The tool makes possible the simultaneous examination of the influence of semi-specificity, multivalency, and ligand diffusion on lectin-glycan recognition. The analysis of the lectin-glycan recognition pattern becomes highly accessible, flexible, and inexpensive. End users can conduct measurements in their own laboratories without specialized equipment by following a step-by-step guide included in the sophisticated modeling software. The detection tool is compatible with a variety of glycan-binding species, including toxins, bacteria, viruses, and cancer cells; consequently, it can benefit a wide range of scientific communities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.