Development of a Joint UC Berkeley/UCSF X-Ray Crystallography Beamline

加州大学伯克利分校/加州大学旧金山分校联合开发 X 射线晶体学光束线

• 批准号: 9977768
• 负责人: Thomas Alber
• 金额: $ 79.2万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2002-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9977768&HistoricalAwards=false
• 关键词: Development; Joint; UC; Berkeley; UCSF

9977768AlberAbstract Synchrotron sources are playing an increasing role in solving the most difficult and important problems in structural biology. However, x-ray beamlines are oversubscribed by over three-fold worldwide, leading to long delays in data collection , prohibiting exploratory experiments and slowing the pace of research. More beam lines are necessary to meet current demand. This project involves the construction of a bright, medium energy, tunable x-ray beamline at the Advanced Light Source (ALS) at Lawrence Berkeley National Laboratory (LBNL) using an ALS x.1 bend magnet source. Favorable characteristics of the ALS and x-ray optics developed at LBNL will allow adjustment of the x-ray beam dimensions to match conventional samples as well as microcrystals. As a result of the high intensity of the beam, reading out the detector will be a rate limiting step in many experiments. The endstation will match the capabilities of the x-ray beam and meet the technical requirements for most crystallographic work. Key features include a CCD detector, two-theta adjustment, accurate crystal positioning optics, cryogenic sample cooling , beam collimation, high-end computational resources and suitable safety systems. A user-friendly facility, incorporating new automated methods for data processing, structure determination, model building and refinement will make the beam line ideal for expert and novice users alike and provide an excellent training setting. The participating faculty at UCB and UCSF have a strong record of leadership in structural biology. Current focus areas include gene regulation, signal transduction, DNA replication and repair, HIV physiology, enzymes, drug targets and complexes, membrane proteins, structural genomics, molecular motors, splicing, translational regulation protein folding and design, RNA recognition, and protein secretion. Regular, rapid access to x-ray beam lines will expedite these projects. The intensity and capability for multiwavelength anomalous diffraction (MAD) experiments will make the beamline suitable for the vast majority of crystallographic projects. The ability to analyze microcrystals will accelerate conventional, functionally motivated studies and reduce the current requirements for crystal optimization. Together, these features will advance even extremely difficult projects that generally require extensive screening to find suitable, strongly-diffracting crystals. The beam line is designed to be a low cost, facility suitable for all but the most demanding studies. It will represent a prototype for a work-horse facility. This development strategy will allow relieve pressure at the very high intensity beam lines at the Advanced Photon Source, leaving those facilities open for projects that require the most intense source of x-rays. The beam line will be jointly funded and operated by the UCSF and UCB investigators who will utilize 75% of the beam time. At least 25% of the beam time will be made available to worldwide users on a competitive basis. An advisory committee of eminent structural biologists will help make global decisions about operations.

9977768AlberAbstract 同步加速器源在解决结构生物学中最困难和最重要的问题中发挥着越来越大的作用。 然而，X 射线束线在全球范围内超额使用了三倍以上，导致数据收集长期延迟，禁止探索性实验并减慢研究速度。 需要更多的光束线才能满足当前的需求。 该项目涉及在劳伦斯伯克利国家实验室 (LBNL) 的先进光源 (ALS) 中使用 ALS x.1 弯曲磁体源构建明亮、中等能量、可调谐 X 射线光束线。 劳伦斯伯克利国家实验室开发的 ALS 和 X 射线光学器件的有利特性将允许调整 X 射线束尺寸，以匹配传统样品和微晶体。 由于光束强度高，在许多实验中读出检测器将成为速率限制步骤。 终端站将与 X 射线束的功能相匹配，并满足大多数晶体学工作的技术要求。 主要功能包括 CCD 探测器、二θ调整、精确的晶体定位光学器件、低温样品冷却、光束准直、高端计算资源和合适的安全系统。 用户友好的设施结合了用于数据处理、结构确定、模型构建和细化的新自动化方法，将使光束线成为专家和新手用户的理想选择，并提供出色的培训环境。 加州大学伯克利分校和加州大学旧金山分校的参与教师在结构生物学领域拥有良好的领导记录。 目前的重点领域包括基因调控、信号转导、DNA复制和修复、HIV生理学、酶、药物靶点和复合物、膜蛋白、结构基因组学、分子马达、剪接、翻译调控蛋白质折叠和设计、RNA识别和蛋白质分泌。 定期、快速访问 X 射线束线将加快这些项目的进程。 多波长反常衍射 (MAD) 实验的强度和能力将使光束线适用于绝大多数晶体学项目。 分析微晶的能力将加速传统的、功能性的研究，并降低当前对晶体优化的要求。 这些功能共同推动了极其困难的项目，这些项目通常需要进行广泛的筛选才能找到合适的强衍射晶体。 光束线被设计成一种低成本的设施，适合除最苛刻的研究之外的所有研究。 它将代表主力设施的原型。 这一开发策略将能够缓解先进光子源极高强度光束线的压力，使这些设施对需要最强 X 射线源的项目开放。该光束线将由 UCSF 和 UCB 研究人员共同资助和运营，他们将利用 75% 的光束时间。 至少 25% 的光束时间将在竞争的基础上提供给全球用户。 由著名结构生物学家组成的咨询委员会将帮助做出有关运营的全球决策。