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

将 Thermo LTQ 升级为 LTQ Orbitrap XL ETD 质谱仪

• 批准号: 7794442
• 负责人: C Robert Matthews
• 金额: $ 50万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-18 至 2011-06-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7794442
• 关键词: Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Area; Biological; Chemicals; Core Facility; Development; Diabetes Mellitus; Disease; Electron Transport; Funding; Human Pathology; Immune response; Information Systems; Lead; MHC Class II Genes; Mass Fragmentography; Mass Spectrum Analysis; Massachusetts; Measurement; Medical; Modeling; Molecular; Neurodegenerative Disorders; Peptides; Performance; Post-Translational Protein Processing; Protein Conformation; Proteins; Proteome; Proteomics; RNA Interference; Reproducibility; Research; Research Personnel; Research Project Grants; Resolution; Role; Scanning; Scientist; Services; Site; System; Techniques; Therapeutic; Universities; Virus Diseases; Water; base; crosslink; glucose transport; improved; insight; instrument; mass spectrometer; medical schools; metabolomics; mutant; population based; protein complex; protein folding; public health relevance; therapeutic development

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.

描述（由申请人提供）：马萨诸塞大学医学院（UMMS）的蛋白质组学和质谱核心设施为UMMS的200多名调查人员提供蛋白质组学和代谢组学服务，并负责维护削减的设施，以使我们的科学家能够使分子级别的科学家获得广泛的生物和医疗问题。为了履行这项责任，我们要求资金升级我们的Thermofisher LTQ线性离子陷阱质谱系统到LTQ Orbitrap ETD XL模型，并购买Waters纳米含量UPLC系统，以用作光谱仪的集成入口。所需的升级将提供对我们的几个项目所需的高质量分辨率（100,000）和高质量精度（<2 ppm）分析的高动态范围（> 3,000）的访问权限，并提供了其他项目所需的其他项目所需的电子传输分解（ETD）技术。 Waters NanoAcquity UPLC将通过Thermo Xcalibur数据系统直接控制光谱仪来提供很高的色谱效率和可重复性，从而显着提高LTQ Orbitrap的性能。该仪器将大大提高我们为7位具有NIH资助的研究人员的主要用户组提供蛋白质表征和蛋白质组学服务的能力。它还将为其他由NIH资助的设施使用者提供更广泛的分析，而我们的Waters NanoAcquility UPLC-Q/TOF Premier仪器或我们设施中的其他仪器目前都可以提供更广泛的分析。该仪器将大大增强的项目包括深度蛋白质组识别，大型MHC II类肽的识别，蛋白质构象的确定和蛋白质复合物内的蛋白质构象和接触点，并通过化学交联，通过化学交联，基于蛋白质交换的蛋白质折叠和基于蛋白质种群的蛋白质种群对蛋白质的蛋白质疾病分析蛋白质的蛋白质折叠的蛋白质折叠，对蛋白质的分析蛋白质疾病的蛋白质疾病分析蛋白质疾病中的蛋白质疾病分析。由于马萨诸塞州中部没有学术研究工具具有所需工具的能力，因此购买该工具将对UMMS的研究产生重大影响。 公共卫生相关性：将从该仪器中受益的研究项目涵盖了广泛的生物学和生物医学领域：（1）神经退行性疾病的分子基础，例如阿尔茨海默氏病和肌萎缩性侧向硬化； （2）对病毒疾病的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。获得的独特而有力的见解将提高我们对疾病分子基础的理解，从而为开发一系列人类病理的治疗治疗提供了理由。