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

职业：快速 H/D 交换质谱：识别聚糖异构体和糖复合物动力学的新方法

基本信息

批准号：
1945078
负责人：
Elyssia Gallagher
金额：
$ 65.5万
依托单位：
Baylor University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2025-05-31
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1945078&HistoricalAwards=false
关键词：
CAREER Rapid Exchange Mass Spectrometry

项目摘要

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.

在化学系化学测量和成像计划的支持下，贝勒大学的Elyssia Gallagher教授和她的团队正在开发新的方法来研究碳水化合物的糖链的结构和变化，这些糖链参与了许多生物过程，包括分子识别、细胞信号和免疫反应。加拉格尔小组正在开发的方法将提供新的工具，将多糖的结构与其生物功能联系起来。加拉格尔小组还在实施一项全面的教育计划，旨在提高化学教师的能力。K-12科学教师需要继续接受高水平内容和主动学习科学教育法方面的培训，以便他们能够以吸引学生兴趣的方式教授当代科学。加拉格尔博士和她的团队正在举办暑期研讨会，向K-12教师介绍先进的化学概念，并开发主动学习活动和教案，以便广泛传播。氢/氢交换质谱仪(HDX-MS)已成为分析蛋白质动力学和结合作用的标准方法。然而，葡聚糖羟基的交换速率在微秒到毫秒的数量级--比传统HDX研究的典型研究要快。加拉格尔小组正在开发和验证快速、可重复性的HDX-MS方法，以准确地表征多糖结构和动力学。具体地说，加拉格尔团队正在开发和利用电喷雾电离过程中的快速HDX(称为In-ESI HDX)，将其与离子迁移率和串联MS相结合，以分离和鉴定碳水化合物和葡聚糖异构体。他们还应用了In-ESI HDX-MS来监测糖结合物中存在的糖链动态的变化。这种可重复使用的方法可以监测所需时间范围内的交换，以便能够分析多糖和糖共轭的结构和生物特性。该奖项反映了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。