National Resource for Imaging Mass Spectrometry

国家成像质谱资源

• 批准号: 7923127
• 负责人: CLAUDE P LECHENE
• 金额: $ 112.61万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7923127
• 关键词: Automation; Biochemistry; Biomedical Research; Calcium; Cell Lineage; Cells; Cellular biology; Collaborations; Communities; Complex; Computer software; DNA; Data; Development; Educational process of instructing; Educational workshop; Enzymes; Fatty Acids; Feasibility Studies; Fractionation; Generations; Goals; Human Resources; Iceberg; Image; Image Analysis; Individual; Iodine; Ions; Isotopes; Label; Laboratories; Lateral; Mass Spectrum Analysis; Measurement; Measures; Metabolic Pathway; Metabolism; Methods; Microbe; Microbiology; Nitrogen Fixation; Nucleic Acids; Pathology; Penetration; Pharmaceutical Preparations; Pharmacology; Population; Procedures; Proteins; RNA; Relative (related person); Research Personnel; Resolution; Resources; Scheme; Signal Transduction; Stem Cell Research; Stem cell transplant; Stem cells; Techniques; Technology; Time; Tracer; Training; Transplantation Immunology; Virus; analytical method; anticancer research; biomedical scientist; experience; interest; ion source; mass spectrometer; method development; migration; new technology; novel; protein degradation; repository; stable isotope; standard measure; sugar; theories; tomography; transmission process; virology; web site

DESCRIPTION (Provided by Applicant): This Resource develops and uses Multi-isotope Imaging Mass Spectrometry (MIMS), the combination of a novel type of secondary ion mass spectrometer with tracer methods and intensive quantitative image analysis. MIMS provides high mass separation (M/AM > 10,000) at high secondary ion transmission, high spatial resolution (35 nm) and has the unique capability of simultaneously recording several atomic mass images. Of the utmost importance, MIMS makes it possible for the first time, at the intracellular level, to simultaneously image the distribution and measure the accumulation of molecules labeled with any isotopes, in particular with stable isotopes, for example 15N. Thus, MIMS allows one to study the localization, the accumulation and the turnover of proteins, fatty acids, sugars and foreign molecules in cellular micro domains; the expression and distribution of DNA and RNA; the migration of donor cells to receiver niches, the nesting of stem cell and the intracellular localization of drugs. Finally, the use of stable isotopes opens a world of labeling possibilities that should revive and expand the use of tracers in humans. The Resource collaborates with researchers in cell biology, pathology, biochemistry, immunology, transplantation, pharmacology, stem cell research, microbiology and virology. Development of an iodine negative primary ion source will open subcellular isotope ratio imaging of secondary positive ions, in particular the experimental use of the multiple stable isotopes of calcium to dissect the function of this essential and ubiquitous intracellular agent, and the quantitative imaging of metallo-enzymes. Study of secondary ion formation will guide labeling schemes. Development of automation will allow us to perform complex analyzes 24/7, decomposing a cell from top to bottom in a succession of hundreds of quantitative atomic mass images, each obtained from the sputtering of a few atomic layers. Powerful software will allow us to rapidly extract and reduce quantitative information from reams of data and in a 3D space. Development of methods for long term labeling of cellular DNA will directly benefit immunology, transplantation, stem cell and cancer research. We will train users by organizing yearly workshop on the theory and practice of MIMS and a workshop on the use of the MIMS data reduction software. We will continue to accumulate on the Resource website information spanning all our procedures, results and happenings. We will make of our Web Site a centralized repository for ourselves and the community of users. This Resource is developing multi-isotope imaging mass spectrometry (MIMS), a new technology that makes it possible to image and quantify molecules within individual mammalian or bacterial cells. Called 'an imaging revolution' as quoted by J. Weitzman (2006, J. Biol. 5:16), MIMS will help solving intractable problems in all fields of biomedical research.

描述（由申请人提供）：该资源开发和使用多同位素成像质谱（MIMS），一种新型的二次离子质谱仪与示踪剂方法和密集的定量图像分析的组合。 MIMS在高二次离子透射率、高空间分辨率（35 nm）下提供高质量分离（M/AM > 10，000），并且具有同时记录多个原子质量图像的独特能力。最重要的是，MIMS首次能够在细胞内水平上同时对任何同位素标记的分子的分布进行成像并测量其累积，特别是稳定同位素，例如15 N。因此，MIMS允许人们研究蛋白质、脂肪酸、糖和外来分子在细胞微域中的定位、积累和周转; DNA和RNA的表达和分布;供体细胞向受体小生境的迁移，干细胞的嵌套和药物的细胞内定位。最后，稳定同位素的使用开启了一个标记可能性的世界，应该恢复和扩大示踪剂在人类中的使用。 该资源与细胞生物学、病理学、生物化学、免疫学、移植、药理学、干细胞研究、微生物学和病毒学的研究人员合作。碘负一次离子源的发展将开启二次正离子的亚细胞同位素比成像，特别是实验使用钙的多种稳定同位素来剖析这种必需的和普遍存在的细胞内试剂的功能，以及金属酶的定量成像。二次离子形成的研究将指导标记方案。自动化的发展将使我们能够全天候进行复杂的分析，从上到下分解一个细胞，连续生成数百个定量原子质量图像，每个图像都是通过溅射几个原子层获得的。强大的软件将使我们能够从大量数据和3D空间中快速提取和减少定量信息。长期标记细胞DNA的方法的发展将直接有益于免疫学、移植、干细胞和癌症研究。我们将通过组织关于MIMS理论和实践的年度研讨会以及关于使用MIMS数据简化软件的研讨会来培训用户。我们将继续在资源网站上积累涵盖我们所有程序、结果和事件的信息。我们将使我们的网站成为我们自己和用户社区的集中存储库。 该资源正在开发多同位素成像质谱（MIMS），这是一种新技术，可以对单个哺乳动物或细菌细胞内的分子进行成像和定量。正如J. Weitzman（2006，J.Biol.5：16）所引用的，MIMS被称为“成像革命”，它将有助于解决生物医学研究所有领域中的棘手问题。