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 东南高分子机器显微镜中心 (SECM4) 是一个联盟 东部联合地区 15 所大学/医疗中心共有 19 名研究人员 研究各种重要生物医学项目的国家，其可变性如高分辨率 病毒结构、膜蛋白结构、各类大分子复合物、一些 以活性形式从细胞、细菌超微结构、肌丝、剪接体中分离出来， 核糖体复合物所有这些都将受益于易于获得高分辨率电子 显微镜，例如配备直接电子探测器 (DED) 的 Titan Krios。人类健康 影响范围从病毒和细菌病原体延伸到对疾病的理解 因基因突变而产生。正在研究癌症和心脏病的基础生物学 在几个成员实验室。佛罗里达州立大学的泰坦·克里奥斯 (Titan Krios) 自2009年开始运营，最近将其图像记录装置从CCD升级为 相机连接到 Direct Electron LLC，DE-20 直接电子探测器，位于现有的 成像滤光片可去除非弹性散射电子，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，我们建议根据当前使用的同步加速器模板创建一个设施 全国各地的多个站点 X 射线晶体学束线，用户可通过该束线进行运输 样本给我们并观察从显微镜中收集到的数据 他们熟悉自己实验室的范围。我们将提供充分的预处理 联盟成员可以评估获得最终高分辨率结构的前景 来自样本的损坏和运动校正的“电影”图像。结果将是一个模型 利用高端仪器进行高通量结构测定，可以揭示 复杂大分子和亚细胞结构的内部运作。