A new tool for the analysis of glycan recognition by lectin

获得这一奖项后，化学系的生命过程化学项目将资助德克萨斯A&A&M大学的Hung-Jen Wu博士和Joseph Kuan博士开发下一代糖阵列工具，该工具可用于研究多糖和凝集素之间的复杂相互作用，这两种凝集素都是在生命系统中发现的生物分子。更具体地说，凝集素是识别和结合多聚糖的蛋白质，多聚糖是碳水化合物分子；凝集素和多聚糖之间的结合在广泛的生理和病理过程中发挥着重要作用。凝集素-葡聚糖结合有几个重要的特征。首先，它不是高度特异的；凝集素通常以不同的亲和力结合到不同的糖链结构上。大多数凝集素通过多价相互作用与糖链结合，即一个凝集素的多个结合域同时与多个糖链分子相互作用。此外，附着在脂质或膜蛋白上的葡聚糖可以扩散到二维细胞膜上。这些特征将凝集素-葡聚糖相互作用区别于经典的双分子相互作用，如抗体和抗原之间的相互作用。现有的凝集素分析方法缺少这些基本特征，因此往往不能描述糖生物学中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-多糖识别原理成为可能。该项目还包括开发一个以项目为基础的学习计划，重点是支持高中生学习化学和纳米科学主题。学生参与了动手实验和互动活动。吴博士和权博士的团队正在将教育项目转变为面向教师的开放访问网络课程，目标是增加他们在STEM外展工作中的影响。吴和权正在开发一种高通量纳米立方体传感器阵列，以在模拟细胞膜的环境中定量测量凝集素-葡聚糖相互作用。此外，正在开发一种动力学蒙特卡罗模拟来模拟复杂的凝集素-葡聚糖相互作用。这种新型的糖阵列工具集分析分析和计算建模于一体，可以测量基本的微观结合参数，进而可以用于预测复杂细胞表面的凝集素功能。该工具可以同时检测半特异性、多价性和配基扩散对凝集素-葡聚糖识别的影响。凝集素-葡聚糖识别模式的分析变得高度可访问、灵活和廉价。最终用户可以在自己的实验室中进行测量，而不需要专门的设备，只需遵循复杂的建模软件中包含的分步指南。该检测工具与多种葡聚糖结合物种兼容，包括毒素、细菌、病毒和癌细胞；因此，它可以造福于广泛的科学界。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.