Cryogenic Electron Microscopy Core

低温电子显微镜核心

• 批准号: 10242902
• 负责人: Dmitry Lyumkis
• 金额: $ 50.9万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242902
• 关键词: Address; Anisotropy; Automobile Driving; Biochemical; Biological; Biology; Classification; Collaborations; Complex; Core Facility; Coupled; Cryoelectron Microscopy; Crystallization; Data; Data Collection; Development; Docking; Electron Microscopy; Evolution; Future; Generations; Goals; HIV; HIV Infections; Heterogeneity; Image Analysis; Knowledge; Label; Lead; Macromolecular Complexes; Maps; Methods; Mind; Modeling; Molecular; Molecular Structure; Paper; Phase; Process; Proteins; Protocols documentation; RNA; Research Personnel; Resolution; Resource Sharing; Ribosomes; Sampling; Services; Specimen; Standardization; Structure; Techniques; Technology; Time; Viral; Virus Replication; Vision; X-Ray Crystallography; antiretroviral therapy; base; computerized data processing; cryogenics; data acquisition; density; experience; image processing; insight; instrument; laboratory experience; macromolecule; member; molecular modeling; new technology; novel; novel strategies; operation; particle; screening; structural biology; tool; viral resistance

ABSTRACT Single-particle cryogenic-electron microscopy (cryo-EM) has revolutionized structural biology through its ability to tackle and elucidate structures of numerous macromolecular complexes that have previously been impervious to structural studies. Over the last several years, it has become increasingly clear that some inherent advantages in cryo-EM make it more suitable to structural studies of certain macromolecules, especially those that are large, dynamic, difficult to purify, and/or poorly biochemically behaved. Cryo-EM has therefore quickly become a mainstay in structural biology. Core 1 will employ the latest generation tools in single-particle cryo-EM for the purpose of specifically addressing structural questions relevant to the HIVE P50 center. The tools will be used to solve structures of macromolecular complexes that are involved in the HIV lifecycle, including viral replication, integration, assembly, and maturation, and will thus expand the evolving structural knowledge underlying the molecular processes associated with HIV infection. This in turn will broadly facilitate the improvement of antiretroviral therapies and lead to a better understanding of viral resistance. The Cryo-EM core will: provide basic services that will evaluate sample quality and feasibility of high-resolution studies, a service that will be available to all HIVE members; provide advanced expertise in structural biology to jointly drive high-resolution structure determination in collaboration with several key investigators; apply ongoing or novel technical developments to specific projects on a per-need basis. Core 1 will thus be highly interactive within, and an integral part of, the HIVE center and will coordinate with all its investigators to different extents.

抽象的 单粒子低温电子显微镜（Cryo-EM）通过其能力彻底改变了结构生物学 处理和阐明许多大分子复合物的结构 对结构研究不可渗。在过去的几年中，越来越明显的是 冷冻EM的固有优势使其更适合某些大分子的结构研究， 尤其是那些大型，动态，难以净化和/或生化性差的人。冷冻em有 因此，迅速成为结构生物学的中流stay。核心1将在 单粒子冷冻EM的目的是针对与Hive P50相关的结构问题 中心。这些工具将用于求解与HIV有关的大分子复合物的结构 生命周期，包括病毒复制，整合，组装和成熟，因此会扩大不断发展的 与HIV感染相关的分子过程的结构知识。这反过来将大致 促进抗逆转录病毒疗法的改善，并更好地理解病毒抗性。这 Cryo-Em Core将：提供基本服务，以评估样本质量和高分辨率的可行性 研究，所有Hive成员都可以使用的服务；提供结构生物学的高级专业知识 与几位主要研究人员合作，共同推动高分辨率结构确定；申请 持续或新颖的技术发展对特定项目的范围为基础。核心1因此将是高度的 在蜂巢中心的内部和不可或缺的一部分互动，并将与所有研究人员进行协调 不同的范围。