MALDI-TOF/TOF MS TO SUPPORT BIOMEDICAL RESEARCH

MALDI-TOF/TOF MS 支持生物医学研究

• 批准号: 8247392
• 负责人: Catherine E. Costello
• 金额: $ 59万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247392
• 关键词: 11 year old; Amyloidosis; Biomedical Research; Boston; Carbohydrates; Cardiovascular Diseases; Communicable Diseases; Complex; Data; Electrospray Ionization; Funding; Glycolipids; Health; Human; Human Milk; Huntington Disease; Image; Joints; Laboratories; Lyme Arthritis; Malignant Neoplasms; Mass Spectrum Analysis; Minor; Prion Diseases; Protein Array; Reflex action; Research; Research Personnel; Research Project Grants; Resolution; Rheumatoid Arthritis; Rivers; Sampling; Services; Sickle Cell Anemia; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Surveys; System; Time; Tissue Sample; Traumatic Brain Injury; United States National Institutes of Health; Universities; college; familial Alzheimer disease; improved; instrumentation; liquid chromatography mass spectrometry; mass spectrometer; medical schools; meetings; protein structure; two-dimensional

DESCRIPTION (provided by applicant): Within the Center for Biomedical Mass Spectrometry, the BUSM Mass Spectrometry Shared Instrumentation Laboratory operates three mass spectrometers (a Thermo-Fisher LTQ-Orbitrap, a Bruker Daltonics Reflex IV MALDI-TOF MS and a Bruker SolariX 12-T UPLC-FTMS), that are dedicated to meeting the increasing and complex needs of NIH-funded investigators. We propose to replace and upgrade the 11-year-old Reflex IV by purchasing and installing a Bruker Daltonics ultrafleXtreme MALDI-TOF/TOF Mass Spectrometer system to provide reliability and access to support services that are no longer available for the Reflex IV and to give improved sensitivity and the additional capabilities for obtaining high resolution mass spectra, tandem mass spectra and two-dimensional imaging. This system will offer high throughput, will facilitate the identification of peaks observed in MALDI-TOF mass spectra to assist in the structural determinations of post-translationally modified proteins and structure elucidation of carbohydrates and glycolipids, and will enable imaging of 2-D samples, to support the human health-related projects described in this proposal. The system will furnish MS and MS/MS spectra and surveys of 2-D targets such as protein arrays, thin layer chromatographic plates and tissue samples. The requested system will improve the efficiency of the Mass Spectrometry Shared Instrumentation Laboratory because unknown peaks will be able to be identified directly from MALDI MS data, thus shortening analysis time, diminishing the need for subsequent LC/MS/MS analyses and increasing the information that can be obtained for samples that are not appropriate for electrospray ionization. The research topics include Cardiovascular Disease, Alzheimer Disease, familial and sporadic systemic amyloid diseases, prion diseases, Cancer, Huntington Disease, Lyme and Rheumatoid Arthritis, Sickle Cell Disease, Traumatic Brain Injury, infectious diseases and characterization of protective components in human milk. Ten Major and six Minor research projects are proposed. All investigators are currently involved in research projects that rely upon the Reflex IV MALDI-TOF MS system that will be retired. Most of the investigators are located on the BUSM campus; the projects the four outside investigators, who are located at the Boston University Charles River Campus, Boston College and Harvard Medical School, have joint funding with CBMS investigators. PUBLIC HEALTH RELEVANCE: The clinical and basic research of the Major Users includes cardiovascular disease (Cohen), (Cohen), cancer (Goldberg) Alzheimer Disease and Traumatic Brain Injury (Goldstein), protein misfolding in prion and systemic amyloid diseases (Harris, Seldin) protective components in human milk (Newburg), Lyme disease and rheumatoid arthritis (Steere), other infectious organisms (Samuelson and Robbins), and wound healing in the eye (Trinkaus-Randall). Projects of the Minor Users address leukemia and breast cancer (Denis, Lerner), sexually transmitted disease (Fichorova), tumor growth (Rahimi), sickle cell disease (Steinberg), and Huntington Disease (Sherman). The proposed instrument system will accelerate progress towards diagnosis and treatment based on understanding the mechanisms of these diseases and conditions and will thus contribute directly toward improving human health.

描述（由申请人提供）：在生物医学质谱中心内，BUSM 质谱共享仪器实验室运行三台质谱仪（Thermo-Fisher LTQ-Orbitrap、Bruker Daltonics Reflex IV MALDI-TOF MS 和 Bruker SolariX 12- T UPLC-FTMS），致力于满足 NIH 资助的研究人员日益增长和复杂的需求。我们建议通过购买和安装 Bruker Daltonics ultrafleXtreme MALDI-TOF/TOF 质谱仪系统来更换和升级已有 11 年历史的 Reflex IV，以提供可靠性并获得 Reflex IV 不再提供的支持服务提高灵敏度和附加功能 用于获得高分辨率质谱、串联质谱和二维成像。该系统将提供高通量，将有助于识别 MALDI-TOF 质谱中观察到的峰，以协助翻译后修饰蛋白质的结构测定以及碳水化合物和糖脂的结构阐明，并将实现二维样品的成像，支持本提案中描述的人类健康相关项目。该系统将提供 MS 和 MS/MS 谱图以及二维目标的调查，例如蛋白质阵列、薄层色谱板和组织样本。所要求的系统将提高质谱共享仪器实验室的效率，因为未知峰将能够直接从 MALDI MS 数据中识别出来，从而缩短分析时间，减少后续 LC/MS/MS 分析的需要，并增加可用于分析的信息。对于不适合电喷雾电离的样品可以获得。研究主题包括心血管疾病、阿尔茨海默病、家族性和散发性系统性淀粉样蛋白疾病、朊病毒病、癌症、亨廷顿病、莱姆病和类风湿性关节炎、镰状细胞病、创伤性脑损伤、传染病和特征 母乳中的保护成分。提出了十个主要研究项目和六个小型研究项目。目前，所有研究人员都参与了依赖于即将退役的 Reflex IV MALDI-TOF MS 系统的研究项目。大多数研究人员都位于 BUSM 校园内；该项目的四名外部研究人员分别位于波士顿大学查尔斯河校区、波士顿学院和哈佛医学院，与 CBMS 研究人员共同资助。 公共健康相关性：主要用户的临床和基础研究包括心血管疾病（Cohen）、（Cohen）、癌症（Goldberg）阿尔茨海默病和创伤性脑损伤（Goldstein）、朊病毒中的蛋白质错误折叠和系统性淀粉样蛋白疾病（Harris、Seldin） ）母乳中的保护成分（Newburg）、莱姆病和类风湿性关节炎（Steere）、其他传染性 有机体（萨缪尔森和罗宾斯）和眼睛伤口愈合（特林考斯-兰德尔）。未成年人用户的项目涉及白血病和乳腺癌（Denis、Lerner）、性传播疾病（Fichorova）、肿瘤生长（Rahimi）、镰状细胞病（Steinberg）和亨廷顿病（Sherman）。拟议的仪器系统将在了解这些疾病和病症的机制的基础上加速诊断和治疗的进展，从而直接为改善人类健康做出贡献。