A NEW HYBRID DIFFRACTOMETER FOR MACROMOLECULAR CRYSTALLOGRAPHY AND SAXS AT TJU

天津大学用于高分子晶体学和 SAXS 的新型混合衍射仪

• 批准号: 8639253
• 负责人: Gino Cingolani
• 金额: $ 60万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639253
• 关键词: Anodes; Area; Basic Science; Biomedical Research; Cancer Biology; Cancer Center; Core Facility; Cost Sharing; Crystallography; Data; Data Collection; Development; Doctor of Philosophy; Equipment; Failure; Fees; Funding; Goals; Housing; Hybrids; Image; Institution; Left; Light; Maintenance; Minor; Mission; Molecular Biology; Research; Research Project Grants; Resource Sharing; Roentgen Rays; Services; Solutions; Source; Spottings; Staging; Synchrotrons; System; Techniques; Testing; Tube; United States National Institutes of Health; Universities; Wages; Work; X-Ray Crystallography; aged; anticancer research; beamline; clinical application; cryogenics; detector; improved; instrumentation; medical schools; programs; screening; seal; structural biology

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.

描述（由申请人提供）：Kimmel癌症中心（KCC）的X射线晶体学和大分子表征共享资源设施，用于支持用于癌症生物学的尖端结构和分子生物学研究，是Thomas Jefferson University（TJU）的11个NCI核心核心设施之一。由于它有潜力增强现有的NIH资助研究计划并进一步开发TJU研究中心的研究，因此X射线晶体学是我们杰斐逊医学院院长Tykocinski博士确定的技术，用于战略我们的研究任务。我们现有的两个X射线发电机在11到22年之间，限制了我们目前执行最前沿结构性工作的能力。较旧的衍射仪（1991年10月安装） 由于旋转阳极不断失败，于2010年9月被用户退役。自2002年2月以来，年轻的单元是密封的X射线管运行，也容易出现频繁的服务故障，昂贵的维护，并提供了非常弱的X射线梁。因此，作为成本分担计划的一部分，旨在在TJU建立最先进的结构生物学中心，我们要求资金 用Rigaku Micromax-007HF旋转阳极X射线发电机双重收集的数据收集，用Rigaku Micromax-007hf旋转阳极旋转阳极旋转阳极旋转阳极旋转阳极和小角度X射线散射（SAXS）配备数据收集。我们已经确定了来自TJU内部的9个主要核心用户和2个次要用户以及急切地支持该建议的附近机构。如果获得资助，TJU将利用我们目前的Rigaku衍射仪派生的约280,000美元的零件来利用这一支持，并资助支持博士学位的30％的级别设施经理Anshul Bhardwaj博士。 KCC还将注入四年的额外资金，以支付Bhardwaj博士薪金和设备维护费用的剩余70％。在计划阶段，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当前发电机的完美功能性部分（即R轴IV ++成像板区域检测器，XStream 2000低温系统等），而右端口将托管新的BioSaxs-1000单元。 Micromax-007HF具有独特的70 UM圆形焦点，非常适合快速对小晶体进行房屋筛查。初步测试还表明，rigaku BioSaxs-1000单元在国家同步灯源（NSLS）上提供了可比质量与光束线X9的SAXS数据。此外，拟议的Rigaku系统的常规维护需求低于我们合并的现有设备的常规维护需求。通过提高X射线光束强度并扩大了解决方案SAXS分析的能力，该拟议的仪器将显着提高当前NIH资助的研究项目的竞争力，并将用户的体系扩展到我们的NCI资助的设施，以最终的目的，以提高我们生物医学研究的质量，并增强基础研究及其临床研究及其癌症研究之间的关系。

项目成果

Three-dimensional structure of human cyclooxygenase (hCOX)-1.

• DOI: 10.1038/s41598-021-83438-z
• 发表时间: 2021-02-22
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Miciaccia M;Belviso BD;Iaselli M;Cingolani G;Ferorelli S;Cappellari M;Loguercio Polosa P;Perrone MG;Caliandro R;Scilimati A
• 通讯作者: Scilimati A

The effects of molecular crowding and CpG hypermethylation on DNA G-quadruplexes formed by the C9orf72 nucleotide repeat expansion.

• DOI: 10.1038/s41598-021-02041-4
• 发表时间: 2021-12-01
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Ozcan KA;Ghaffari LT;Haeusler AR
• 通讯作者: Haeusler AR

Structure of the pre-mRNA leakage 39-kDa protein reveals a single domain of integrated zf-C3HC and Rsm1 modules.

• DOI: 10.1038/s41598-022-22183-3
• 发表时间: 2022-10-21
• 期刊: Scientific reports
• 影响因子: 4.6