MALDI-TOF/TOF MS TO SUPPORT BIOMEDICAL RESEARCH

描述(申请人提供)：在生物医学质谱学中心内，BUSM质谱学共享仪器实验室运营着三台质谱仪(一台Thermo-Fisher LTQ-Orbitrap、一台Bruker Daltonics Reflex IV MALDI-TOF MS和一台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 Ultrafleme MALDI-TOF/TOF质谱仪系统来更换和升级已有11年历史的Reflex IV，以提供可靠性和访问Reflex IV不再提供的支持服务，并提供更高的灵敏度和更多功能 用于获得高分辨率质谱图、串联质谱图和二维成像。该系统将提供高通量，将促进在MALDI-TOF质谱图中观察到的峰的识别，以帮助翻译后修饰蛋白质的结构确定以及碳水化合物和糖脂的结构阐明，并将使二维样品成像，以支持本提案中描述的与人类健康相关的项目。该系统将提供MS和MS/MS光谱，以及对蛋白质阵列、薄层色谱板和组织样品等二维目标的调查。所要求的系统将提高质谱学共享仪器实验室的效率，因为可以直接从MALDI MS数据中识别未知峰，从而缩短分析时间，减少对后续LC/MS/MS分析的需要，并增加对不适合电喷雾电离的样品可以获得的信息。研究主题包括心血管疾病、阿尔茨海默病、家族性和散发性全身性淀粉样变性疾病、普恩疾病、癌症、亨廷顿病、莱姆病和类风湿性关节炎、镰刀细胞病、创伤性脑损伤、感染性疾病和 母乳中的保护性成分。提出了10个重大研究项目和6个次要研究项目。所有研究人员目前都参与了依赖Reflex IV MALDI-TOF MS系统的研究项目，该系统将退役。大多数调查人员位于BUSM校区；四名外部调查人员位于波士顿大学查尔斯河校区、波士顿学院和哈佛医学院，他们与CBMS调查人员共同资助项目。 公共卫生相关性：主要使用者的临床和基础研究包括心血管疾病(科恩)、癌症(戈德堡)、阿尔茨海默病和创伤性脑损伤(戈德斯坦)、普恩蛋白错误折叠和全身性淀粉样蛋白疾病(哈里斯、塞尔丁)、母乳中的保护成分(纽堡)、莱姆病和类风湿性关节炎(STEER)、其他感染性疾病 生物体(Samuelson和Robbins)和眼睛的伤口愈合(Trinkaus-Randall)。少数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)、镰状细胞疾病(Steinberg)和亨廷顿病(Sherman)。拟议的仪器系统将在了解这些疾病和疾病的机制的基础上加快诊断和治疗的进展，从而将直接有助于改善人类健康。

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.