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