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

[9977768]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方面发挥着越来越大的作用。然而，x射线束线在全球范围内被超过三倍，导致数据收集长时间延迟，禁止探索性实验，减缓了研究步伐。需要更多的波束线来满足目前的需求。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弯曲磁铁源构建明亮，中等能量，可调谐的x射线光束线。在LBNL开发的ALS和x射线光学的有利特性将允许调整x射线束尺寸以匹配常规样品和微晶体。由于光束的高强度，在许多实验中读出探测器将是一个限制速率的步骤。终端站将匹配x射线束的能力，并满足大多数晶体学工作的技术要求。主要特点包括CCD探测器、2 -theta调节、精确的晶体定位光学、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，结合新的自动化方法的数据处理，结构的确定，模型的建立和完善，将使光束线理想的专家和新手用户一样，并提供了一个很好的培训设置。UCB和UCSF的参与教师在结构生物学方面有着很强的领导能力。目前关注的领域包括基因调控、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、快速进入x射线束线将加快这些项目。多波长异常衍射（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。分析微晶体的能力将加速传统的、功能驱动的研究，并减少当前对晶体优化的要求。总之，这些特性将推进那些通常需要大量筛选才能找到合适的、强衍射晶体的极其困难的项目。光束线的设计是一个低成本的设施，适合所有的，但最苛刻的研究。它将代表一个驮马设施的原型。这种发展策略将减轻先进光子源的高强度光束线的压力，使这些设施对需要最强烈x射线源的项目开放。这条波束线将由UCSF和UCB的研究人员共同资助和运营，他们将利用75%的波束时间。至少25%的波束时间将在竞争的基础上提供给全球用户。一个由著名结构生物学家组成的咨询委员会将帮助制定有关操作的全球决策。

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.