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A shared macromolecular X-ray diffraction system in Rochester

罗彻斯特共享的高分子 X 射线衍射系统

基本信息

批准号：
7791902
负责人：
Joseph E Wedekind
金额：
$ 47.79万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-02-01 至 2011-01-31
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：罗彻斯特大学医学中心已经将x射线晶体学作为战略发展的一个领域，因为它对现有的nih资助的研究项目和中心有很大的影响。这个计划的一个限制因素是我们目前的x射线仪器在12到14岁之间。因此，设备容易出现频繁的服务故障，维护成本高，并且缺乏一个强大的机制来提供非专业人员的访问。作为建立最先进的共享x射线核心设施的费用分摊计划的一部分，我们要求资金用现代化的高通量仪器取代我们老化的系统。如果获得资助，医疗中心管理部门将利用这一支持，注入额外的资金，为博士级设施管理人员提供资金，并支付维护费，以确保在五年内共享核心可访问性和功能。已经确定了七个主要核心用户，他们手中有晶体，需要仪器访问-附近罗切斯特理工学院的一个区域用户也有晶体。在规划阶段，我们的测试表明，布鲁克AXS I？S微聚焦密封管X射线源，集成光学元件，APEX II CCD探测器，Oxford 700冷流和电动测角仪头（用于快速定心）安装在一个4圆平台上，与我们目前的内部系统相比，将加速用户整个过程的五倍或更多。布鲁克多层Quazar光学产生的0.120毫米光束尺寸非常适合于小晶体的快速筛选，这是大多数实验的典型。该系统还能够在测试中处理295个单位的电池边缘。值得注意的是，布鲁克AXS系统的日常维护需求相对较少，其服务合同比我们现有的设备低近50%。通过增加吞吐量和扩大用户可访问性的范围，我们相信提议的共享x射线核心将大大提高目前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。这些中心代表了有针对性的研究论坛，将正在为改善公共卫生而战的临床和基础研究人员联合起来。