Tools For High-Throughput High-Resolution Three Dimensional Electron Microscopy

高通量高分辨率三维电子显微镜工具

• 批准号: 9318780
• 负责人: SCOTT M STAGG
• 金额: $ 31.94万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9318780
• 关键词: Biological; Complex; Computer software; Data; Data Collection; Detection; Devices; Dimensions; Disease; Dose; Electron Microscopy; Electrons; Financial compensation; Generations; Health; Human; Image; Microfluidics; Molecular; Motion; Negative Staining; Performance; Preparation; Proteins; Reproducibility; Research; Research Infrastructure; Research Personnel; Resolution; Sampling; Series; Side; Software Tools; Specimen; Structure; System; Techniques; Time; beta-Galactosidase; computerized data processing; cryogenics; density; detector; electron tomography; falls; human disease; imaging modality; improved; innovation; molecular assembly/self assembly; particle; protein complex; protein structure; reconstruction; screening; tomography; tool

Summary Three-dimensional electron microscopy (3DEM) is a set of techniques for determining the structures of large proteins and protein complexes. It has been shown that cryogenic EM (cryo-EM) has the ability to determine structures to high enough resolution to unambiguously place side chains in the EM density. Though cryo-EM is increasingly reaching near-atomic resolution, a number of hurdles are present in order to achieve side-chain level resolution structure determination of low-symmetry and no symmetry complexes. Here we propose to develop tool to facilitate high-throughput high-resolution 3DEM. In the first aim, we propose to develop tools to enable automated specimen preparation and screening, and enable a new tools for direct electron detection. In the second aim, we propose to develop tools for tomographic data collection and processing including exploring new modalities for image acquisition and for developing an infrastructure for processing tomographic subvolumes. This research will benefit human health by facilitating the determination of protein structures that are relevant for human disease.

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