Mass Spectrometer for Biomedical Research

用于生物医学研究的质谱仪

• 批准号: 7215065
• 负责人: MICHAEL L GROSS
• 金额: $ 50万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2008-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7215065
• 关键词: Acquired Immunodeficiency Syndrome; Anesthesia procedures; Antigens; Arts; Binding; Binding Sites; Biomedical Research; Calcium-Binding Proteins; Cancer Pain Management; Cell physiology; Centrosome; Clinic; Communities; Development; Diabetes Mellitus; Disease; EF Hand Motifs; Electrons; Excision; Funding; GABA Receptor; Gene Silencing; HIV; Histones; Hybrids; Hydroxyl Radical; Immunity; Indiana; Laboratories; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Metals; Minor; Mitochondrial Proteins; Nucleotide Excision Repair; Oxidation-Reduction; Pain management; Patients; Peptides; Pongidae; Post-Translational Protein Processing; Property; Proteins; Proteomics; Public Health; Reaction; Research; Research Personnel; Role; Services; Source; Staging; Steroids; Structure; System; Treatment Protocols; UV induced; Universities; Washington; Work; base; endonuclease; human centrin-2 protein; instrument; ionization; mass spectrometer; method development; nano; protein structure; repair enzyme; repaired

DESCRIPTION (provided by applicant): We propose to acquire a state-of-the-art hybrid mass spectrometer (i.e., a Thermo-Electron Orbitrap or equivalent) for core and collaborative research and to provide service to the biomedical research community at Washington University (WU) and nationwide. Interfaced to the mass spectrometer will be a nano-HPLC. An autosampler and nanospray ionization source will be provided by the host laboratory to complete the installation. The integrated system will provide a platform for the separation and analysis of biomolecules, especially peptides as antigens or from post-translationally modified proteins. One specific aim of this acquisition is to further the NIH-funded research of eight major users: (1) Finding diabetogenic peptides presented by MHCs (Dr. Emil R. Unanue, WU), (2) Locating steroid binding sites on GABA receptors for anesthesia and pain management (Dr. Alex Evers, WU), (3) Mapping out the expression of the mitochondrial proteins in HIV patients at various stages of the disease and during different treatment regimens (Dr. Kevin Yarasheski, WU), (4) Finding the role of posttranslational modifications of histones in nucleolar dominance and gene silencing (Dr. Craig Pikaard, WU), (5) Studying DNA damage and repair mechanisms involved in UV-induced photodamage to DNA (Dr. John-Stephen Taylor, WU), (6) Determining protein structure and interactions using H/D exchange and fast hydroxyl radical reactions (Dr. Michael Gross, WU), (7) Studying the structure and metal-binding properties of human centrin 2, an EF-hand calcium binding protein important in centrosome function, cell duplication, and nucleotide excision repair (Dr. Rajiv Kumar, Mayo Clinic), (8) Finding the mechanism of redox activity in Ape-1 endonuclease, a base excision repair enzyme expressed in several cancers (Dr. Millie Georgiadis, Indiana University). The second specific aim is to provide accurate mass and occasional proteomics mass spectrometry service, including method development, to minor and new users and in so doing, stimulate the development of new collaborative research. Five of the above NIH-funded projects arose from this kind of preliminary work. Relevance This instrument acquisition has direct impact on the public health by supporting forefront research on immunity and diabetes, anesthesia and pain management, cancer, and AIDS. In addition, it will have broad impact by providing nationwide mass spectrometry service for researchers whose MS requirements are sufficiently simple that they do not require collaborative efforts.

描述（由申请人提供）：我们建议购买一台最先进的混合质谱仪（即热电子轨道阱或同等设备）用于核心和协作研究，并为华盛顿大学的生物医学研究界提供服务（WU）和全国。与质谱仪连接的是纳米高效液相色谱仪。主机实验室将提供自动进样器和纳喷雾电离源来完成安装。该集成系统将为生物分子（尤其是作为抗原的肽或翻译后修饰的蛋白质）的分离和分析提供平台。此次收购的一个具体目的是进一步推进 NIH 资助的八个主要用户的研究：(1) 寻找 MHC 呈现的糖尿病肽（Emil R. Unanue 博士，WU），(2) 定位 GABA 受体上的类固醇结合位点麻醉和疼痛管理（Alex Evers 博士，WU），(3) 绘制 HIV 患者在疾病不同阶段和不同治疗方案期间线粒体蛋白的表达（Kevin Yarasheski 博士，WU），(4) 寻​​找组蛋白翻译后修饰在核仁优势和基因沉默中的作用（Craig Pikaard 博士，WU），(5) 研究 UV 诱导光损伤中涉及的 DNA 损伤和修复机制DNA（John-Stephen Taylor 博士，WU），(6) 使用 H/D 交换和快速羟基自由基反应确定蛋白质结构和相互作用（Michael 博士） Gross, WU), (7) 研究人中心蛋白 2 的结构和金属结合特性，中心蛋白 2 是一种 EF 手钙结合蛋白，对中心体功能、细胞复制和核苷酸切除修复很重要（Dr. Gross，WU）。 Rajiv Kumar，梅奥诊所），(8) 寻找 Ape-1 核酸内切酶的氧化还原活性机制，Ape-1 核酸内切酶是一种在多种癌症中表达的碱基切除修复酶（Millie Georgiadis 博士，印第安纳大学）。第二个具体目标是向未成年用户和新用户提供精确质量和偶尔的蛋白质组学质谱服务，包括方法开发，从而刺激新合作研究的发展。上述 NIH 资助的项目中有五个来自此类前期工作。相关性 该仪器的采购通过支持免疫和糖尿病、麻醉和疼痛管理、癌症和艾滋病的前沿研究，对公共健康产生直接影响。此外，它将通过为那些质谱要求足够简单、不需要协作努力的研究人员提供全国范围内的质谱服务而产生广泛的影响。