A shared macromolecular X-ray diffraction system in Rochester

描述(由申请人提供)：罗切斯特大学医学中心将X射线结晶学作为战略发展领域，因为它可能对现有的NIH资助的研究项目和中心产生很大影响。这项计划的一个限制因素是，我们目前的X射线仪器使用年限在12到14年之间。因此，设备容易出现频繁的服务故障，维护费用昂贵，并且缺乏可靠的机制来向非专家提供服务。作为建立最先进的共享X射线核心设备的成本分担计划的一部分，我们请求提供资金，以现代的、更高吞吐量的仪器取代我们陈旧的系统。如果获得资金，医疗中心管理部门将通过注入额外资金来利用这一支持，以提供一名博士级别的设施经理以及维护费，以确保在五年内共享核心可访问性和功能。已经确定了一个由七个主要核心用户组成的小组，他们手中有水晶，需要访问仪器--附近罗切斯特理工学院的一名地区用户也有水晶。在规划阶段，我们的测试表明，布鲁克AXS I？S微焦点密封管X射线源、集成光学元件、APEX II CCD探测器、牛津700冷流和电动测角仪头(用于快速样品居中)安装在4个圆形平台上，与我们目前的内部系统相比，将使用户吞吐量提高5倍或更多。布鲁克的多层Quazar光学系统产生的0.120 mm光束尺寸非常适合于快速筛选小晶体，这是大多数实验的典型特征。所提出的系统还能够在测试中处理295个单元的边缘。值得注意的是，布鲁克AXS系统的日常维护需求相对较低，其服务合同比我们现有的设备低近50%。通过提高吞吐量和扩大用户可及性范围，我们有信心拟议的共享X射线核心将显著增强目前由NIH资助的研究项目的竞争力。这一共享资源将与现有核心和中心的研究目标相结合，如艾滋病研究发展中心、高通量筛选(HTS)核心和RNA生物学中心：从基因组到医学。这样的中心代表着有针对性的研究论坛，将正在为改善公共卫生而发动战争的临床和基础研究人员联合起来。 健康相关性：X射线结晶学是一项有价值的技术，可以使生物分子可视化，并了解它们与人类疾病相关的作用机制。罗切斯特大学的结晶学仪器有12-14年的历史，这阻碍了我们做出新发现的能力，也阻碍了我们的科学家访问。我们要求一个最先进的系统，该系统将作为共享资源进行维护，并与我们现有的NIH资助的战略中心的目标相结合，这些中心的主要任务是改善公共卫生。

DESCRIPTION (provided by applicant): The University of Rochester Medical Center has targeted X-ray crystallography as an area for strategic development due to its potential for high impact on existing NIH-funded research programs and Centers. A limiting factor in this plan is that our current X-ray instrumentation is between 12 and 14 years old. As such, the equipment is prone to frequent service failures, costly maintenance, and lacks a robust mechanism to provide access to non-specialists. As part of a cost-sharing plan to establish a state-of-the-art, shared X-ray core facility, we request funds to replace our aged system with a modern, higher-throughput instrument. If funded, the Medical Center administration will leverage this support by infusing additional funds that provide for a PhD-level facility manager, as well as maintenance fees, to assure shared core accessibility and functionality for a period of five years. A group of seven major core users has already been identified who have crystals in hand and require instrument access - a regional user from the nearby Rochester Institute of Technology also has crystals. In the planning stages, our tests indicated that the Bruker AXS I?S microfocus sealed tube X- ray source, integrated optics, APEX II CCD detector, Oxford 700 cold stream and motorized goniometer head (for rapid sample centering) mounted on a 4-circle platform would accelerate user throughout by five-fold or more compared to our current in-house system. The 0.120 mm beam size produced by Bruker's multilayer Quazar optic is well suited for rapid screening of small crystals, which are typical of most experiments. The proposed system was also capable of handling a 295 ¿ unit cell edge in tests. Significantly, the routine maintenance needs of the Bruker AXS system are relatively modest, and its service contracts are nearly fifty percent lower than our existing equipment. By increasing throughput and expanding the scope of user accessibility, we are confident that the proposed shared X-ray core will significantly enhance the competitiveness of current NIH-funded research projects. This shared resource will be integrated with the research goals of existing Cores and Centers, such as the Developmental Center for AIDS Research, the High Throughput Screening (HTS) Core, and The Center for RNA Biology: From Genome to Medicine. Such Centers represent forums of targeted research that unite clinical and basic researchers who are waging a war to improve public health. HEALTH RELEVANCE: X-ray crystallography is a valuable technique to visualize biological molecules and to understand their mechanisms of action in relation to human disease. The crystallography instrumentation at the University of Rochester is 12-14 years old, which impedes our ability to make new discoveries and hampers access by our scientists. We request a state-of-the-art system that will be maintained as a shared resource, and integrated with the goals of our existing NIH-funded strategic Centers whose primary mission is to improve public health.