High Speed Detector for Time-Resolved Research at BioCARS

BioCARS 用于时间分辨研究的高速探测器

• 批准号: 7836715
• 负责人: JOHN Keith MOFFAT
• 金额: $ 170.94万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-19 至 2015-05-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7836715
• 关键词: 7 year old; Animals; Area; Biohazardous Substance; Cells; Charge; Chicago; Coupled; Crystallography; Devices; Drug Design; Enzymes; Funding; Health Services Research; Human; Insecta; Insulin; Journals; Laboratories; Life; Molecular Mechanisms of Action; National Center for Research Resources; Paper; Pattern; Peer Review; Photons; Plants; Positioning Attribute; Publishing; Qualifying; Reaction; Research; Roentgen Rays; Scientist; Source; Speed; Spottings; Structure; Synchrotrons; Time; United States National Institutes of Health; Universities; Virus; West Nile virus; X-Ray Crystallography; base; design and construction; detector; interest; millisecond; pathogen; research and development; research study; structural biology

DESCRIPTION (provided by applicant): The project requests funds for purchase of a state-of-the-art, large area, fast readout, charge coupled device, X-ray area detector and detector mount, to be installed on the 14-ID-B insertion device beam line operated by BioCARS/University of Chicago at the Advanced Photon Source, Argonne National Laboratory. This beam line is the flagship of a national facility for synchrotron-based structural biology funded since 1992 by NCRR/NIH. The facility is open to all qualified scientists, and is one of the most productive beam lines at the Advanced Photon Source as judged by the number of peer- reviewed scientific papers - including those in the top journals - published annually by our BioCARS users. The facility offers world-leading capabilities in time-resolved single crystal diffraction, and in the safe examination of biohazards at the BSL3 level. BioCARS research and development has concentrated on applications in time- resolved X-ray crystallography. Our users conduct both collaborative and service research in that area and in somewhat more conventional, static crystallography. Our present seven-year-old X-ray detector has a relatively small active area and a relatively long readout time, which renders it unsuited to many user experiments. The first precludes its use at long crystal-to-detector distances, which both enhances the background and hinders the separation of diffraction spots from crystals with large unit cells; the second makes it unsuitable for recording sequential diffraction patterns in the millisecond time range, as is advantageous for following slower, often irreversible reactions in this range. The new detector requires the design, construction and installation of a fully-automated mount, to position the detector flexibly with respect to the crystal and X-ray beam. Crystals to be examined using this detector by our users include those of pathogenic viruses, some of which e.g. West Nile virus are human pathogens and others of which are animal, plant or insect pathogens. Other crystals are of more direct biomedical interest e.g. crystals of insulin converting enzymes, in which a successful structure determination may open up leads for structure-based drug design. Yet others are studied from the point of view of elucidating their molecular mechanism of action, by time-resolved or static crystallography. Again, an understanding of mechanism (and in particular, of the structures of short-lived intermediates) directly underpins drug design.

描述（由申请人提供）：该项目要求购买最先进的，大面积，快速读数，充电耦合设备，X射线区域探测器和检测器安装座，将安装在Argonne National National Laboratory的Argonne Nationne National Laboratory的芝加哥大学芝加哥大学的14-ID-B插入设备梁线上。该光束线是NCRR/NIH自1992年以来基于同步加速器的结构生物学的国家设施的旗舰。该设施均向所有合格的科学家开放，并且是高级光子源最有生产力的光束线之一，这是由同行评审的科学论文数量（包括在顶级期刊中）每年由我们的生物阶段用户发布的。该设施在时间分辨的单晶衍射以及BSL3级别的生物危害方面提供了世界领先的功能。 生物验入的研究和开发集中在时间分辨的X射线晶体学上的应用。我们的用户在该领域以及更常规的静态晶体学进行了协作和服务研究。我们目前的七岁X射线检测器的活动面积相对较小，读取时间相对较长，这使其不适合许多用户实验。首先排除了其在长晶体到检测器距离上的使用，这既增强了背景，又阻碍了衍射斑与具有大型单位细胞的晶体的分离。第二个使其不适合在毫秒时间范围内记录顺序衍射模式，这对于遵循此范围内较慢（通常是不可逆的反应）是有利的。新的检测器需要完全自动化的安装座的设计，构造和安装，以相对于晶体和X射线梁灵活地定位探测器。 使用我们的用户使用该检测器检查的晶体包括病毒病毒的晶体，其中一些病毒例如西尼罗河病毒是人类病原体，其他病原体是动物，植物或昆虫病原体。其他晶体具有更直接的生物医学兴趣，例如转化酶的胰岛素晶体，其中成功的结构测定可能为基于结构的药物设计打开潜在客户。然而，从时间分辨或静态晶体学阐明其分子作用机理的角度研究了其他人。同样，对机制（尤其是对短寿命中间体的结构）的理解直接为药物设计。