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.

项目描述（由申请人提供）：该项目要求资金用于购买最先进的，大面积，快速读出，电荷耦合装置，x射线区域探测器和探测器支架，安装在由BioCARS/芝加哥大学在阿贡国家实验室先进光子源操作的14-ID-B插入装置光束线上。这条光束线是自1992年以来由NCRR/NIH资助的基于同步加速器的结构生物学国家设施的旗舰。该设施向所有合格的科学家开放，并且是先进光子源中最具生产力的光束线之一，这是由我们的BioCARS用户每年发表的同行评审科学论文数量判断的-包括那些在顶级期刊上的论文。该设施在时间分辨单晶衍射和BSL3级生物危害的安全检查方面具有世界领先的能力。BioCARS的研究和开发主要集中在时间分辨x射线晶体学方面的应用。我们的用户在该领域进行协作和服务研究，在某种程度上更传统，静态晶体学。我们目前使用了7年的x射线探测器具有相对较小的活跃区域和相对较长的读出时间，这使得它不适合许多用户实验。第一个问题阻碍了它在晶体到探测器的较长距离上的应用，这既增强了背景，又阻碍了衍射点与大晶胞晶体的分离；第二个缺点使得它不适合记录毫秒时间范围内的连续衍射图案，而这对于跟踪这个范围内较慢的、通常不可逆的反应是有利的。新的探测器需要设计、建造和安装一个全自动安装架，以便根据晶体和x射线束灵活地定位探测器。我们的用户使用该检测器检测的晶体包括致病性病毒的晶体，其中一些如西尼罗河病毒是人类病原体，另一些是动物、植物或昆虫病原体。其他晶体具有更直接的生物医学意义，例如胰岛素转化酶晶体，其中成功的结构确定可能为基于结构的药物设计开辟线索。然而，从阐明它们的分子作用机制的角度出发，通过时间分辨或静态晶体学进行了研究。再一次，对机制的理解（特别是对短寿命中间体结构的理解）直接支撑着药物设计。