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)：该项目申请资金用于购买最先进的大面积快速读出设备、电荷耦合设备、X射线面积探测器和探测器支架，安装在由BioCARS/芝加哥大学在Argonne国家实验室高级光子源操作的14-ID-B插入设备光束线上。这条束流线是自1992年以来由NCRR/NIH资助的基于同步加速器的国家结构生物学设施的旗舰产品。该设施对所有合格的科学家开放，从我们的BioCARS用户每年发表的同行评议的科学论文(包括顶级期刊上的论文)的数量来看，它是先进光子源中生产率最高的光束线之一。该设施在时间分辨单晶衍射以及在BSL3级别的生物危害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射线结晶学的应用上。我们的用户在该领域以及在某种程度上更传统的静态结晶学方面进行合作和服务研究。我们目前使用了七年的X射线探测器的有效区域相对较小，读出时间相对较长，这使得它不适合许多用户实验。第一种方法排除了它在长晶体到探测器的距离上的使用，这既增强了背景，又阻碍了从具有大晶胞的晶体中分离衍射点；第二种方法使其不适合在毫秒时间范围内记录连续的衍射图，这有利于在该范围内跟踪较慢的、通常不可逆的反应。新的探测器需要设计、建造和安装一个全自动安装装置，以便探测器相对于晶体和X射线束灵活定位。我们的用户使用该探测器检查的晶体包括致病病毒的晶体，其中一些例如西尼罗河病毒是人类病原体，其他是动物、植物或昆虫病原体。其他晶体具有更直接的生物医学意义，如胰岛素转换酶晶体，其中成功的结构测定可能为基于结构的药物设计开辟线索。还有一些是从阐明它们的分子作用机制的角度来研究的，通过时间分辨或静态结晶学。同样，对机理的理解(特别是对短命中间体的结构)的理解直接支持药物设计。