A NEW HYBRID DIFFRACTOMETER FOR MACROMOLECULAR CRYSTALLOGRAPHY AND SAXS AT TJU

描述(由申请人提供)：金梅尔癌症中心(KCC)的X射线结晶学和高分子表征共享资源设施致力于支持应用于癌症生物学的尖端结构和分子生物学研究，是托马斯·杰斐逊大学(TJU)由NCI支持的11个核心设施之一。由于它有潜力加强现有的NIH资助的研究项目，并进一步发展TJU研究中心的研究，X射线结晶学是我们的杰斐逊医学院院长Tykocinski博士为我们的研究任务战略发展确定的技术之一。我们现有的两台X射线发生器已有11到22年的历史，限制了我们目前进行尖端结构工作的能力。较旧的衍射仪(1991年10月安装) 由于旋转阳极不断出现故障，已于2010年9月退役给用户。较年轻的装置是一种密封的X射线管，自2002年2月开始运行，也容易出现频繁的服务故障，维护费用高昂，提供的X射线束非常弱。因此，作为在TJU建立最先进的结构生物学中心的成本分担计划的一部分，我们请求提供资金 用Rigaku MicroMax-007HF微焦点旋转阳极X射线发生器取代这两台老化的衍射仪，该发生器同时配备了从大分子晶体收集数据和小角X射线散射(SAXS)。我们已确定一组由9名主要核心用户和2名次要用户组成的小组，他们来自TJU内部和附近机构，他们热切地支持这项建议。如果获得资金，TJU将利用这一支持，从我们目前的Rigaku衍射仪获得约28万美元的部件，并为30%的博士级设施经理Anshul Bhardwaj博士提供资金。KCC还将注入四年的额外资金，以支付Bhardwaj博士剩余70%的工资和设备维护费。在规划阶段，我们的初步测试表明，Rigaku MicroMax-007HF非常适合我们的需求。该系统允许我们重新利用电流发生器的完美功能部件(即R轴IV++成像板面积探测器、XStream 2000低温系统等)。在左侧端口，而右侧端口将容纳新的BioSAXS-1000单元。MicroMax-007HF具有独特的70微米圆形焦斑，非常适合于对小晶体进行快速室内筛选。初步测试还表明，Rigaku BioSAXS-1000装置提供的SAXS数据质量与国家同步加速器光源(NSLS)的光束线X9相当。此外，拟议的Rigaku系统的日常维护需求低于我们现有设备的组合。通过增加X射线束强度和扩展我们的解决方案SAXS分析能力，拟议的仪器将显著增强当前NIH资助的研究项目的竞争力，并将用户群体扩大到我们的NCI资助的设施，最终目标是提高我们的生物医学研究的质量，并加强基础研究、癌症研究及其临床应用之间的联系。

DESCRIPTION (provided by applicant): The X-ray Crystallography and Macromolecular Characterization Shared Resource Facility at the Kimmel Cancer Center (KCC), dedicated to supporting cutting edge structural and molecular biology research applied to cancer biology, is one of the 11 NCI-supported Core Facilities at Thomas Jefferson University (TJU). Because of its potential to enhance existing NIH-funded research programs and further develop research at TJU research centers, X-ray crystallography is one of the techniques identified by Dr. Tykocinski, our Dean of Jefferson Medical College, for strategic development of our research mission. Our existing two X-ray generators are between 11 and 22 years old, limiting our current ability to carry out cutting edge structural work. The older diffractometer (installed in Oct 1991) was decommissioned to users in Sept 2010 due to constant failure in the rotating anode. The younger unit, a sealed X-ray tube operational since Feb 2002, is also prone to frequent service failures, costly maintenance and provides a very weak X-ray beam. Therefore, as part of a cost-sharing plan to establish a state-of-the-art center for structural biology at TJU, we request funds to replace both aged diffractometers with a Rigaku MicroMax-007HF microfocus rotating anode X-ray generator dual equipped for data collection from macromolecular crystals and Small Angle X-Ray Scattering (SAXS). We have identified a group of 9 major core users and 2 minor users from both inside TJU and in nearby institutions who eagerly support this proposal. If funded, TJU will leverage this support with ~$280,000 in parts derived from our current Rigaku diffractometer, and funds supporting 30% of a Ph.D.-level facility manager, Dr. Anshul Bhardwaj. The KCC will also infuse four years of additional funds to cover the remaining 70% of Dr. Bhardwaj salary and equipment maintenance fees. In the planning stages, our preliminary tests indicated that the Rigaku MicroMax-007HF is ideally suited for our needs. This system allows us to re-utilize perfectly functional parts of our current generator (i.e. R-AXIS IV++ imaging plate area detector, XStream 2000 cryogenic system, etc.) in the left port, while the right port will host the new BioSAXS-1000 unit. With a unique 70 um circular focal spot, the MicroMax-007HF is perfectly suited for rapid in house screening of small crystals. Preliminary tests have also shown that the Rigaku BioSAXS-1000 unit provided SAXS data of comparable quality as beamline X9 at the National Synchrotron Light Source (NSLS). Additionally, the routine maintenance needs of the proposed Rigaku system are lower than that of our combined existing equipment. By increasing X-ray beam intensity and expanding our capabilities for in solution SAXS analysis, the proposed instrumentation will significantly enhance the competitiveness of current NIH-funded research projects and expand the body of users to our NCI-funded facility, with the ultimate goal of improving the quality of our biomedical research, and strengthening the liaison between basic research, cancer research and its clinical applications.