The Southeastern Consortium for Microscopy of MacroMolecular Machines

东南宏观分子机器显微镜联盟

• 批准号: 9317510
• 负责人: ESTHER BULLITT
• 金额: $ 47.45万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-18 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317510
• 关键词: 3-Dimensional; Academic Medical Centers; Adenoviruses; Award; BRCA1 gene; Back; Cancer Biology; Cells; Complex; Computer software; Country; Crystallography; DNA Sequence Alteration; Data; Data Analyses; Data Quality; Defect; Devices; Disease; Distant; Dysentery; Electron Microscope; Electron Microscopy; Electrons; Enzymes; Fees; Filament; Florida; Freezing; Grant; Guns; HIV; Health; Health Sciences; Heart Diseases; Human; Image; Institution; Laboratories; Link; Macromolecular Complexes; Massachusetts; Measles virus; Medical center; Membrane Proteins; Microscope; Microscopy; Modeling; Molecular; Motion; Movement; Muscle; Names; Ohio; Optics; Oregon; Papillomavirus; Parkinson Disease; Poliomyelitis; Positioning Attribute; Preparation; Process; Proteins; Recording of previous events; Recruitment Activity; Research; Research Personnel; Resolution; Resources; Retirement; Ribosomes; Robotics; Roentgen Rays; Running; Salmonella typhimurium; Sampling; Scanning; Series; Shigella; Ships; Site; Southeastern United States; Specimen; Spliceosomes; Structure; Subcellular structure; Synchrotrons; System; Three-Dimensional Image; Three-Dimensional Imaging; Time; Titan; Training; United States; United States National Institutes of Health; Universities; Vibrio cholerae; Virus; X-Ray Crystallography; base; charge coupled device camera; computing resources; cost; cryogenics; data acquisition; detector; experience; image processing; improved; instrument; instrumentation; macromolecule; malignant breast neoplasm; member; movie; next generation; novel strategies; operation; particle; pathogen; protein structure; response

Abstract The Southeastern Center for Microscopy of MacroMolecular Machines (SECM4) is a consortium of 15 Universities/Medical Centers with a total of 19 investigators throughout the Eastern United States studying a wide range of important biomedical projects as variable as high resolution virus structure, membrane protein structure, macromolecular complexes of various types, some isolated in active form from cells, bacterial ultrastructure, muscle filaments, spliceosomes, ribosomes complexes all of which will benefit from ready access to a high resolution electron microscope such as a Titan Krios equipped with a direct electron detector (DED). Human health implications extend from virus and bacterial pathogens to the understanding of diseases resulting form genetic mutations. The basic biology of cancer and heart disease is being studied in several member laboratories. The Titan Krios at Florida State University has been in operation since 2009 and recently has had its image recording device upgraded from CCD camera to a Direct Electron LLC, DE-20 direct electron detector positioned ahead of an existing imaging filter which removes inelastically scattered electrons thereby improving the image quality. Although we propose a robust plan to enable members to come to Florida State University, we propose creating a facility based on the synchrotron template currently in use at multiple sites X-ray crystallography beam lines around the country whereby users ship specimens to us and watch the data being collected as it comes off the microscope from the familiar confines of their own laboratories. We will provide sufficient preprocessing that consortium members can evaluate the prospects for obtaining a final high resolution structure from damage and motion corrected “movie” images of their samples. The result will be a model for high throughput structure determination utilizing high-end instrumentation that can reveal the inner workings of complex macromolecules and subcellular structures.

抽象的 大分子机器显微镜（SECM4）是一个财团 在整个东部联合会的15个大学/医疗中心中，共有19名调查员 研究广泛的重要生物医学项目的状态与高分辨率一样可变 病毒结构，膜蛋白结构，各种类型的大分子复合物，有些 从细胞，细菌超微结构，肌肉丝，剪接体，剪接体，孤立的形式分离出活性。 核糖体络合物所有这些都将受益于现成的高分辨率电子 显微镜，例如配备直接电子检测器（DED）的Titan Krios。人类健康 含义从病毒和细菌病原体扩展到对疾病的理解 产生的遗传突变。癌症和心脏病的基本生物学正在研究 在几个成员实验室中。佛罗里达州立大学的泰坦krios曾在 自2009年以来的操作，最近已从CCD升级其图像记录设备 摄像机到直接电子有限责任公司，DE-20直接电子检测器位于现有的之前 成像过滤器，它去除非弹性电子，从而改善图像 质量。尽管我们提出了一个强大的计划，以使成员能够来到佛罗里达州 大学，我们建议创建一个基于当前正在使用的同步器模板的设施 多个站点X射线晶体学横梁线周围用户发货 向我们的标本，观察从显微镜从显微镜中脱离的数据 他们自己的实验室的熟悉范围。我们将提供足够的预处理 财团成员可以评估获得最终高分辨率结构的前景 损坏和运动纠正了样本的“电影”图像。结果将是模型 对于高吞吐量结构的确定，使用高端仪器可以揭示 复杂的大分子和亚细胞结构的内部工作。