The Southeastern Consortium for Microscopy of MacroMolecular Machines

东南宏观分子机器显微镜联盟

基本信息

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
项目类别：
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

项目摘要

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。影响范围从病毒和细菌病原体延伸到对疾病的理解癌症和心脏病的基本生物学正在研究中。佛罗里达州立大学的 Titan Krios 已在多个成员实验室中使用。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用户发货所在国家/地区的多个站点 X 射线晶体学束线样本给我们并观察从显微镜中收集到的数据我们将提供足够的预处理，以确保他们熟悉自己的实验室范围。联盟成员可以评估获得最终高分辨率结构的前景从他们的样本的损坏和运动校正的“电影”图像中得到的结果将是一个模型。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。