National Resource for Imaging Mass Spectrometry

国家成像质谱资源

• 批准号: 8322636
• 负责人: CLAUDE P LECHENE
• 金额: $ 111.49万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8322636
• 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; Image; Image Analysis; Immunology; 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; data reduction; 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）：此资源开发和使用多同位素成像质谱法（MIMS），新型二次离子质谱仪与示踪剂方法的组合以及密集的定量图像分析。 MIMS在高次级离子传输，高空间分辨率（35 nm）下提供高质量分离（M/AM> 10,000），并且具有同时记录几个原子质量图像的独特能力。最重要的是，MIMS首次在细胞内水平上可以同时对分布并测量用任何同位素标记的分子的积累，尤其是稳定的同位素，例如15N。因此，MIMS允许一个人研究细胞微域中蛋白质，脂肪酸，糖和外国分子的定位，积累和周转。 DNA和RNA的表达和分布；供体细胞向接收者壁ches的迁移，干细胞的嵌套以及药物的细胞内定位。最后，稳定同位素的使用开辟了一个标记可能性的世界，这些世界应恢复和扩大人类中示踪剂的使用。 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。碘负初级离子源的开发将打开次级阳性离子的亚细胞同位素比率成像，特别是钙的多个稳定同位素的实验用途，以剖析这种必不可少的和无处不在的细胞内剂的功能，以及金属酶的定量成像。次级离子形成的研究将指导标记方案。自动化的开发将使我们能够进行24/7的复杂分析，并在数百个定量原子质量图像中从上到下分解一个单元，每个细胞都是从几个原子层的溅射中获得的。功能强大的软件将使我们能够从数据的流程和3D空间中快速提取并减少定量信息。长期标记细胞DNA的方法的开发将直接受益于免疫学，移植，干细胞和癌症研究。我们将通过组织有关MIMS理论和实践的年度研讨会以及有关使用MIMS数据减少软件的讲习班来培训用户。我们将继续在涵盖所有程序，结果和事件的资源网站信息上积累。我们将为我们自己和用户社区提供一个集中式存储库。 该资源正在开发多同位素成像质谱法（MIMS），这是一种新技术，可以使单个哺乳动物或细菌细胞内的分子形象形象和量化。 J. Weitzman（2006，J。Biol。5:16）所引用的“成像革命”，MIMS将帮助解决生物医学研究的所有领域中的顽固问题。