Upgrade of Our Thermo LTQ to a LTQ Orbitrap XL ETD Mass Spectrometer

描述(申请人提供)：马萨诸塞大学医学院蛋白质组学和质谱学核心设施为马萨诸塞大学医学院的200多名研究人员提供蛋白质组学和代谢组学服务，并负责维护尖端设施，使我们的科学家能够从分子水平深入了解广泛的生物和医学问题。为了履行这一责任，我们要求提供资金，将我们的ThermoFisher LTQ线性离子陷阱质谱仪系统升级到LTQ Orbitrap ETD XL型号，并购买Waters Nano Acquity UPLC系统作为光谱仪的集成入口。所要求的升级将提供我们几个项目所需的高动态范围(扫描内为3,000)、高质量分辨率(100,000)和高质量精度(&lt；2 ppm)分析，以及其他项目绝对需要的电子转移分解(ETD)技术。Waters Nano Acquity UPLC通过Thermo XCalibur数据系统直接控制光谱仪，提供非常高的色层效率和重现性，从而极大地提高LTQ Orbitrap的性能。这一仪器将极大地提高我们为我们的主要用户群体提供蛋白质表征和蛋白质组学服务的能力，该群体由7名高生产率的NIH资助的研究人员组成。它还将为其他NIH资助的设备用户提供比我们的Waters Nano Acquity UPLC-Q/TOF Premier仪器或我们设施中的其他仪器所提供的更广泛的分析。该仪器将大大增强的项目包括深入的蛋白质组鉴定，鉴定大的MHC II类多肽，通过化学交联确定蛋白质复合体和聚集体中的蛋白质构象和接触点，通过H/D交换对蛋白质折叠动力学进行定点测量，以及对突变的致病蛋白质中不稳定的翻译后修饰进行基于蛋白质种群的分析。由于马萨诸塞州中部没有具备所需仪器能力的学术研究仪器，购买该仪器将对密歇根大学医学科学院的研究产生重大影响。 公共卫生意义：将受益于该仪器的研究项目涵盖广泛的生物和生物医学领域：(1)阿尔茨海默病和肌萎缩侧索硬化症等神经退行性疾病的分子基础；(2)病毒疾病免疫反应的分子基础；(3)葡萄糖转运在糖尿病中的作用；(4)RNAi疗法的发展；(5)蛋白质折叠的分子机制以及错误折叠如何导致疾病。这种独特而强大的见解将增加我们对疾病的分子基础的理解，从而为开发针对一系列人类病理的治疗方法提供理论基础。

DESCRIPTION (provided by applicant): The Proteomics and Mass Spectrometry Core Facility at the University of Massachusetts Medical School (UMMS) provides proteomics and metabolomics services for over 200 investigators at the UMMS and is responsible for maintaining a cutting-edge facility that enables our scientists to acquire molecular-level insights into a broad spectrum of biological and medical problems. To fulfill that responsibility, we request funds to upgrade our ThermoFisher LTQ linear ion trap mass spectrometry system to the LTQ Orbitrap ETD XL model and to purchase a Waters nanoAcquity UPLC system to be used as an integrated inlet for the spectrometer. The requested upgrade will provide access to high dynamic range (>3,000 within scan), high mass resolution (100,000) and high mass accuracy (<2 ppm) analyses required for several of our projects and to the electron transfer decomposition (ETD) technique absolutely required for other projects. The Waters nanoAcquity UPLC will substantially improve the performance of the LTQ Orbitrap by providing very high chromatographic efficiency and reproducibility through direct control of the spectrometer by the Thermo Xcalibur data system. This instrument will dramatically increase our ability to provide protein characterization and proteomics services to our major users group of 7 highly-productive NIH-funded investigators. It will also provide a broader range of analyses for other NIH-funded Facility users than is currently available with our Waters nanoAcquity UPLC-Q/TOF Premier instrument or other instruments in our facility. Projects that would be greatly enhanced by this instrument include in-depth proteome identification, identification of large MHC class II peptides, determination of protein conformation and contact points within protein complexes and aggregates through chemical cross-linking, site-specific measurement of protein folding dynamics by H/D exchange and protein population- based analysis of labile posttranslational modifications in mutant disease-causing proteins. Because there are no academic research instruments in central Massachusetts with the capabilities of the requested instrument, the purchase of this instrument will have a major impact on research at UMMS. PUBLIC HEALTH RELEVANCE: The research projects that will benefit from this instrument span a wide range of biological and biomedical areas: (1) the molecular basis of neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis; (2) the molecule basis for the immune response to viral diseases; (3) the role of glucose transport in diabetes; (4) the development of RNAi therapeutics; and (5) the molecular mechanisms of protein folding and how misfolding can lead to disease. This unique and powerful insights obtained will increase our understanding of the molecular basis for disease and, thereby, provide a rationale for the development of therapeutic treatments for a spectrum of human pathologies.