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 单颗粒低温电子显微镜 (cryo-EM) 凭借其能力彻底改变了结构生物学 解决和阐明先前已被研究的许多大分子复合物的结构 不受结构研究的影响。在过去的几年里，越来越明显的是，一些 冷冻电镜的固有优势使其更适合某些大分子的结构研究， 尤其是那些体积大、动态大、难以纯化和/或生化性能较差的物质。冷冻电镜有 因此很快成为结构生物学的中流砥柱。 Core 1 将采用最新一代工具 单粒子冷冻电镜，专门解决与 HIVE P50 相关的结构问题 中心。这些工具将用于解析与艾滋病毒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，从而扩展不断发展的病毒 与 HIV 感染相关的分子过程的结构知识。这反过来又将广泛 促进抗逆转录病毒疗法的改进并更好地了解病毒耐药性。这 Cryo-EM 核心将： 提供评估样品质量和高分辨率可行性的基本服务 研究，一项将向所有 HIVE 成员提供的服务；提供结构生物学方面的先进专业知识 与几位关键研究人员合作，共同推动高分辨率结构测定；申请 根据需要对特定项目进行持续或新颖的技术开发。因此，核心 1 将高度 HIVE 中心内部的互动，也是 HIVE 中心不可分割的一部分，并将与所有调查人员协调， 不同程度的。