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.

摘要 东南大分子机器显微镜中心(SECM4)是一个联合体 在美国东部的15所大学/医学中心中，共有19名研究人员 各国正在研究范围广泛的重要生物医学项目，如高分辨率一样多变 病毒结构，膜蛋白结构，各种类型的大分子复合体，一些 以活性形式从细胞、细菌超微结构、肌丝、剪接体、 核糖体复合体，所有这些都将受益于随时获得高分辨率电子 显微镜，如配备了直接电子探测器(DED)的泰坦Krios。人类健康 含义从病毒和细菌病原体延伸到对疾病的理解 由基因突变导致的。癌症和心脏病的基础生物学正在研究中 在几个成员实验室。佛罗里达州立大学的泰坦·克里奥斯已经在 自2009年投入运营以来，最近已将其图像记录设备从CCD升级 照相机到Direct Electron LLC，DE-20直接电子探测器位于现有 成像滤光片，去除非弹性散射的电子，从而改善图像 质量。尽管我们提出了一项强有力的计划，使会员能够来到佛罗里达州 大学，我们建议建立一个基于目前正在使用的同步加速器模板的设施 多个地点的X射线结晶学光束线遍布全国各地，用户可通过该线路运输 把标本交给我们，看着从显微镜下收集的数据来自 熟悉他们自己实验室的范围。我们将提供足够的预处理， 联盟成员可以评估获得最终高分辨率结构的前景 从损坏和运动校正的“电影”图像的样品。结果将是一个模型 用于利用高端仪器进行高通量结构确定，该仪器可以揭示 复杂大分子和亚细胞结构的内部工作原理。