权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

CAREER: Chemical Tools for Understanding the Mycomembrane of the Corynebacterineae

职业：了解棒状杆菌亚科菌膜的化学工具

基本信息

批准号：
1654408
负责人：
Benjamin Swarts
金额：
$ 66.15万
依托单位：
Central Michigan University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-05-01 至 2023-09-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1654408&HistoricalAwards=false
关键词：
CAREER Chemical Tools Understanding Mycomembrane

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Benjamin Swarts at Central Michigan University to investigate the structure and dynamics of a unique cell membrane present in hundreds of bacterial species of the suborder Corynebacterineae. All bacteria have cell envelopes with one or two membranes that play critical roles in cellular defense, communication, and structural integrity. Species in the Corynebacterineae have two membranes, the outermost of which is composed mostly of complex sugar-linked lipids called mycolic acid conjugates. This "mycomembrane" is unique to the Corynebacterineae and gives them distinctive physiological and pathogenic characteristics. Many aspects of the production, maintenance, and composition of the mycomembrane remain unknown because of the challenges encountered when using standard experimental techniques. This project generates and utilizes new chemical biology tools to characterize the structure and dynamics of the mycomembrane. The tools being developed form a significant part of the process of acquiring a better understanding of how the Corynebacterineae survive within and adapt to their surrounding environment. In addition, an investigation of this bacterial system advances understanding of the nature of interactions of bacteria with the environment and provides information that would enhance efforts to gain environmental control of pathogens. Undergraduate students and postdoctoral fellows working on this research acquire interdisciplinary training in organic synthesis, microbiology and proteomics. This research is also integrated into an outreach program that introduces community college students to chemical bacteriology research and encourages their continued education in science. The tools generated in this project are expected to have broad utility and to support other scientists pursuing basic and applied research on the Corynebacterineae.Traditional biochemical and molecular biological approaches are not well-suited to investigating the mycomembrane because it is made up largely of non-genetically encoded lipids and sugars. This research project develops chemical probes that exploit native metabolic pathways to introduce tags into specific mycomembrane components in intact bacterial cells. Tagged molecules are then imaged or identified by mass spectrometry, depending on the goal of the experiment. The probes developed in this project provide information on (i) how the major glycolipid constituents of the mycomembrane are synthesized and remodeled when the bacterium encounters stress; and (ii) what proteins reside within and contribute to the construction and maintenance of the mycomembrane. The findings from this project will lead to an improved understanding of mycomembrane structure and dynamics and provide insight into the physiology of bacteria in the Corynebacterineae suborder.

有了这个奖项，化学部的生命过程化学计划正在资助中密歇根大学的Benjamin Swarts博士研究数百种棒状杆菌亚目细菌中存在的独特细胞膜的结构和动力学。所有细菌都有一个或两个膜的细胞包膜，在细胞防御，通信和结构完整性中起着关键作用。棒杆菌科的物种有两层膜，最外面的膜主要由称为分枝菌酸缀合物的复杂糖连接脂质组成。这种“菌膜”是棒状杆菌科所特有的，赋予它们独特的生理和致病特性。由于使用标准实验技术时遇到的挑战，真菌膜的生产，维护和组成的许多方面仍然未知。该项目生成并利用新的化学生物学工具来表征菌膜的结构和动态。正在开发的工具形成了更好地了解Coryneococcineae如何生存和适应周围环境的过程的重要组成部分。此外，对这种细菌系统的调查促进了对细菌与环境相互作用的性质的理解，并提供了将加强对病原体的环境控制的努力的信息。从事这项研究的本科生和博士后获得有机合成，微生物学和蛋白质组学的跨学科培训。这项研究也被整合到一个推广计划，介绍社区大学的学生化学细菌学研究，并鼓励他们在科学继续教育。在这个项目中产生的工具，预计将有广泛的实用性，并支持其他科学家追求的基础和应用研究的Coryneacrobineae.传统的生物化学和分子生物学方法是不适合调查的菌膜，因为它是由非遗传编码的脂质和糖的大部分。该研究项目开发化学探针，利用天然代谢途径将标签引入完整细菌细胞中的特定菌膜成分。标记的分子然后通过质谱成像或识别，这取决于实验的目标。该项目开发的探针提供了以下信息：（i）当细菌遇到压力时，菌膜的主要糖脂成分如何合成和重塑;以及（ii）哪些蛋白质驻留在菌膜内并有助于菌膜的构建和维护。该项目的研究结果将导致对菌膜结构和动力学的更好理解，并提供对棒杆菌亚目细菌生理学的深入了解。