CAREER: Rapid H/D Exchange-Mass Spectrometry: Novel Methods for Identifying Glycan Isomers and Glycoconjugate Dynamics

在化学系化学测量和成像项目的支持下，贝勒大学的Elyssia Gallagher教授和她的团队正在开发新方法来研究聚糖的结构和变化-碳水化合物链参与许多生物过程，包括分子识别，细胞信号传导和免疫反应。Gallagher小组正在开发的方法将提供新的工具，将聚糖的结构与其生物功能联系起来。加拉格尔集团还实施了一项全面的教育计划，旨在提高教师在化学方面的能力。K-12科学教师需要在高水平的内容和主动学习科学教学法的持续培训，使他们能够以吸引学生兴趣的方式教授当代科学。Gallagher博士和她的小组正在举办暑期讲习班，向K-12教师介绍先进的化学概念，并制定积极的学习活动和广泛传播的课程计划。氢/氘交换质谱（HDX-MS）已成为分析蛋白质动力学和结合相互作用的标准方法。然而，聚糖羟基的交换速率在微秒到毫秒的量级上-比常规HDX研究的典型速率快。Gallagher团队正在开发和验证快速、可重复的HDX-MS方法，用于准确表征聚糖结构和动力学。具体而言，Gallagher小组正在开发和利用电喷雾电离期间的快速HDX（称为in-ESI HDX），结合离子迁移率和串联MS，以分离和鉴定碳水化合物和聚糖异构体。 他们还应用in-ESI HDX-MS来监测糖缀合物中聚糖动力学的变化。可重复的方法可以监测交换所需的时间尺度，使分析的结构和生物特性的聚糖和糖缀合物。这个奖项反映了NSF的法定使命，并已被认为是值得支持的评估使用基金会的知识价值和更广泛的影响审查标准。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Elyssia Gallagher and her group at Baylor University are developing new methods to study the structures and changes of glycans - chains of carbohydrates that are involved in many biological processes, including molecular recognition, cellular signaling, and immune responses. The methods being developed by the Gallagher group will provide new tools to correlate the structures of glycans with their biological functions. The Gallagher group is also implementing a comprehensive educational plan designed to increase teacher competency in chemistry. K-12 science teachers need continued training in high-level content and active-learning science pedagogy so that they can teach contemporary science in ways that engage student interest. Dr. Gallagher and her group are hosting summer workshops to introduce K-12 teachers to advanced chemistry concepts and to develop active-learning activities and lesson plans for broad dissemination. Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has become a standard method for analyzing protein dynamics and binding interactions. However, exchange rates of glycan hydroxyls are on the order of microseconds to milliseconds – faster than those typical for conventional HDX studies. The Gallagher group is developing and validating rapid, reproducible HDX-MS methods for accurately characterizing glycan structures and dynamics. Specifically, the Gallagher group is developing and utilizing rapid HDX during electrospray ionization (referred to as in-ESI HDX) coupled to ion mobility and tandem MS, to separate and identify carbohydrate and glycan isomers. They are also applying in-ESI HDX-MS to monitor changes in glycan dynamics when present in glycoconjugates. The reproducible methods can monitor exchange on the timescale needed to enable analysis of the structural and biological properties of glycans and glycoconjugates.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.