IDBR: Development of a Linear Ion Trap/Photodissociation Mass Spectrometer for Biological Research

得克萨斯大学奥斯汀分校的詹妮弗·布罗德贝特博士获得了一项拨款，用于开发一种新的高性能质谱仪，用于表征生物分子。质谱学是目前分析蛋白质和DNA等生物分子的主要分析方法之一。例如，近年来质谱学的进步使蛋白质生物标记物的阐明取得了巨大进展，这些标记物表征了负责细胞中蛋白质合成的核酸。解决日益复杂的生物问题的能力依赖于提高质谱仪的性能，拟议的工作旨在开发一种先进的质谱仪，通过基于激光的方法以高灵敏度激活和裂解感兴趣的生物分子，从而更好地识别生物分子及其突变。该项目的目标是设计、建造、开发和应用高性能串联质谱仪来表征生物分子。该仪器的核心是一个双源/线性离子陷阱/飞行时间质谱仪，配备了两个用于光解的激光。仪器的核心是一个线性离子捕捉器，它将允许优雅的多步骤实验，其中包括用于选择感兴趣的特定离子的离子隔离和用于生物分子分解和结构表征的光解离。该项目将需要建造一个真空室、电路、离子光学、电离源、激光选件、数据采集程序以及所有部件的接口。质谱仪将以模块化的方式建造和测试，并将遵循可测量里程碑的计划。涉及合作的生物应用将在该项目的最后一年开始。在赠款中开发的新质谱仪将允许详细研究蛋白质与蛋白质之间的相互作用，并允许研究一些最具挑战性的生物学问题。德克萨斯大学化学和生物化学系以及细胞和分子生物学研究所的九个研究小组将使用由此产生的质谱仪。未来科学家的教育与实现上述科学目标是同样重要的目标。拟议的项目将涉及每年两名研究生和两名本科生助理的努力。这些学生将接受最先进的分析仪器的设计、开发、建造和测试方面的培训，将获得生物分子表征的经验，并将与参与相关项目的其他研究生合作。由于合作的跨学科性质，来自其他研究小组的许多研究生将接触到基于与Brodbelt？S博士研究生合作开展合作项目的拟议仪器。为了提高人们对先进质谱学解决复杂生物问题能力的认识，Pi Brodbelt将在每个夏季学期开始时开设质谱学培训班。该课程将向化学和生物化学系、细胞和分子生物学研究所以及当地其他大学的全体成员进行宣传。

A grant has been awarded to Dr. Jennifer Brodbelt at the University of Texas at Austin to develop a new high performance mass spectrometer for the characterization of biological molecules. Mass spectrometry is currently one of the premier analytical methods for the analysis of biomolecules such as proteins and DNA. Advances in mass spectrometry in recent years have allowed tremendous inroads in the elucidation of, for example, protein biomarkers that characterize nucleic acids responsible for protein synthesis in cells. The ability to solve increasingly complex biological problems depends on improving the performance of mass spectrometers, and the proposed work aims to develop an advanced mass spectrometer that offers better identification of biological molecules and their mutations by using laser-based methods to activate and cleave the biological molecules of interest with high sensitivity.The goal of the project is the design, construction, development and application of a high performance tandem mass spectrometer for the characterization of biological molecules. The core of the instrument is a dual source/linear ion trap/time-of-flight mass spectrometer equipped with two lasers for photodissociation. The heart of the instrument is a linear ion trap which will allow elegant multi-step experiments that incorporate ion isolation for selection of specific ions of interest and photodissociation for disassembly of biological molecules and structural characterization. The project will entail construction of a vacuum chamber, electrical circuits, ion optics, an ionization source, laser options, data acquisition programs, and interfacing of all the components. The mass spectrometer will be built and tested in a modular fashion, and a plan of measurable milestones will be followed. Biological applications involving collaborations will begin in the final year of the project. The new mass spectrometer developed in the grant will allow detailed studies of protein-protein interactions and allow some of the most challenging biological problems to be studied. Nine research groups within the Department of Chemistry and Biochemistry and Institute for Cellular and Molecular Biology at The University of Texas will use the resulting mass spectrometer. The education of future scientists is an equally important goal as accomplishing the scientific objectives stated above. The proposed project will involve the efforts of two graduate students, along with two undergraduate assistants, each year. These students will be trained in the design, development, construction, and testing of state-of-the art analytical instrumentation, will gain experience with the characterization of biological molecules, and will work cooperatively with other graduate students involved on related projects. Due to the interdisciplinary nature of the collaborations, numerous graduate students from other research groups will be exposed to the proposed instrumentation based on teaming with the Dr. Brodbelt?s graduate students to undertake collaborative projects. To increase the awareness of the capabilities of advanced mass spectrometry for solving complex biological problems, PI Brodbelt will offer a mass spectrometry training course at the beginning of each summer term. The course will be publicized to all members of the Department of Chemistry and Biochemistry and Institute for Cellular and Molecular Biology and other local universities.