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）：马萨诸塞州大学医学院（UMMS）的蛋白质组学和质谱核心设施为UMMS的200多名研究人员提供蛋白质组学和代谢组学服务，并负责维护一个尖端设施，使我们的科学家能够获得分子水平的见解，了解广泛的生物和医学问题。为了履行这一职责，我们申请资金将ThermoFisher LTQ线性离子阱质谱系统升级为LTQ Orbitrap ETD XL型号，并购买一个沃茨nanoAcquity UPLC系统，用作光谱仪的集成入口。所要求的升级将提供我们的几个项目所需的高动态范围（扫描内> 3，000），高质量分辨率（100，000）和高质量精度（<2 ppm）分析以及其他项目绝对需要的电子转移分解（ETD）技术。沃茨nanoAcquity UPLC通过Thermo Xcalibur数据系统直接控制光谱仪，提供非常高的色谱效率和重现性，从而显著提高LTQ Orbitrap的性能。该仪器将大大提高我们为我们的主要用户群提供蛋白质表征和蛋白质组学服务的能力，该用户群由7名高生产率的NIH资助的研究人员组成。与我们的沃茨nanoAcquity UPLC-Q/TOF Premier仪器或我们设施中的其他仪器相比，它还将为其他NIH资助的设施用户提供更广泛的分析。这一仪器将大大加强的项目包括深入的蛋白质组鉴定，鉴定大型MHC II类肽，通过化学交联确定蛋白质构象和蛋白质复合物和聚集体内的接触点，通过H/D交换对蛋白质折叠动力学进行位点特异性测量，以及对突变致病蛋白质中不稳定的翻译后修饰进行基于蛋白质群体的分析。由于马萨诸塞州中部没有具有所需仪器能力的学术研究仪器，购买这种仪器将对UMMS的研究产生重大影响。 公共卫生相关性：受益于该仪器的研究项目涵盖广泛的生物学和生物医学领域：（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）病毒性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疗法的开发;（5）基因治疗的研究。（5）蛋白质折叠的分子机制以及错误折叠如何导致疾病。获得的这种独特而强大的见解将增加我们对疾病分子基础的理解，从而为开发一系列人类病理学的治疗方法提供理论基础。