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，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）的11个NCI支持的核心设施之一。由于其潜力，以加强现有的NIH资助的研究计划，并进一步发展在TJU研究中心的研究，X射线晶体学是由博士Tykocinski，我们的杰斐逊医学院院长，为我们的研究使命的战略发展确定的技术之一。我们现有的两台X射线发生器的使用年限在11至22年之间，限制了我们目前进行尖端结构工作的能力。较旧的衍射仪（安装于1991年10月） 2010年9月，由于旋转阳极不断出现故障，该设备被停用。较年轻的装置是一个密封的X射线管，自2002年2月开始使用，也容易出现频繁的服务故障，维修费用昂贵，并提供非常弱的X射线束。因此，作为在天津大学建立一个最先进的结构生物学中心的费用分摊计划的一部分，我们要求资金 用理学MicroMax-007 HF微焦点旋转阳极X射线发生器替换两台老化的衍射仪，该X射线发生器双配备用于大分子晶体和小角X射线散射（SAXS）的数据收集。我们已经确定了一组9个主要核心用户和2个次要用户，他们来自天津大学内部和附近的机构，热切支持这一提议。如果获得资助，TJU将利用这一支持，从我们目前的理学衍射仪中获得约280，000美元的部件，并资助30%的博士学位。高级设施经理安舒尔·巴德瓦杰博士KCC还将注入四年的额外资金，以支付Bhardwaj博士剩余的70%工资和设备维护费。在规划阶段，我们的初步测试表明理学MicroMax-007 HF非常适合我们的需求。该系统使我们能够重新利用当前发生器的完美功能部件（即R-AXIS IV++成像板面积探测器、XStream 2000低温系统等）。在左边的端口，而右边的端口将托管新的BioSAXS-1000单元。MicroMax-007 HF具有独特的70 um圆形焦斑，非常适合在室内快速筛选小晶体。初步测试还表明，理学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，理学系统的日常维护需求低于我们现有设备的总和。通过增加X射线束强度和扩大我们在溶液SAXS分析的能力，拟议的仪器将显着提高目前NIH资助的研究项目的竞争力，并扩大用户的身体，我们的国家癌症研究所资助的设施，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。

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