High Field Fourier Transform Mass Spectrometer for Biomedical Applications

描述(由申请人提供)：我们寻求获得一个具有电子捕获解离(ECD)的12特斯拉FTMS系统，以将自上而下的蛋白质组学策略应用于各种与人类健康相关的重要项目。为了增强仪器的功能，我们提出了电子转移解离(ETD)和补偿式ICR陷阱来实现一种独特的高端仪器。将应用该工具的项目代表了翻译(与疾病有关的)研究和基础(基础)研究之间的平衡。与疾病相关的研究项目对关节炎、自身免疫、癌症、糖尿病、艾滋病毒和血液疾病的理解和治疗产生了影响。基础科学项目寻求对与麻醉学、细胞信号、能量转移和蛋白质功能、结合和相互作用有关的基本生命过程的理解。每个项目都需要自上而下的蛋白质测序，以解决蛋白质翻译后修饰的整体问题，或者解决蛋白质相互作用和结构变化的生物化学和生物物理学中的重要问题。这些问题不是自下而上的方法可以解决的。今天，高场磁体光谱仪的使用是一个重大挑战。然而，这一独特仪器的研究将指导战略，扩大质谱学在明天探测完整蛋白质和回答系统生物学问题方面的研究作用。公共卫生相关性我们正在提出一种独特的质谱仪系统，该系统将提供无与伦比的能力，以了解包括关节炎、自身免疫、糖尿病、艾滋病毒、血液疾病、麻醉学和一般生物过程在内的一系列疾病。它还将支持旨在研究蛋白质修饰和相互作用基础的基础研究。随着我们发展仪器能力，我们希望找到机会，通过解决以前难以解决的问题来改善人类健康。

DESCRIPTION (provided by applicant): We seek to acquire a 12 Tesla FTMS system with electron-capture dissociation (ECD) to apply top-down proteomics strategies to a variety of important projects relevant to human health. To augment the instrumentation, we propose to implement electron-transfer dissociation (ETD) and a compensated ICR trap to realize a unique high-end instrument. The projects to which the instrument will be applied represent a balance between translational (disease-related) and fundamental (basic) research. The disease-related research projects have impact in the understanding and treatment of arthritis, autoimmunity, cancer, diabetes, HIV, and blood disorders. The basic science projects seek an understanding of basic life processes related to anesthesiology, cellular signaling, energy transfer, and protein function, binding, and interaction. Each project requires top-down protein sequencing to solve ensemble problems of protein post-translational modification or to address important problems in the biochemistry and biophysics of protein interactions and structural change. These problems are not soluble by bottom-up methods. The use of high-field magnet-based spectrometers is a major challenge today. Nevertheless, the research enabled by this unique instrument will direct strategies to expand the role of mass spectrometry for tomorrow's research in probing intact proteins and answering systems biological questions. PUBLIC HEALTH RELEVANCE We are proposing a unique mass spectrometer system that will provide unparalleled capabilities to understand a broad array of diseases including arthritis, autoimmunity, diabetes, HIV, blood disorders, anesthesiology and general biological processes. It will also support basic research aimed at the fundamentals of protein modification and interaction. As we develop the instruments capabilities, we expect to find opportunities to improve human health by solving problems that were previously intractable.