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）：基梅尔癌症中心（KCC）的x射线晶体学和大分子表征共享资源设施，致力于支持尖端结构和分子生物学研究应用于癌症生物学，是美国托马斯杰斐逊大学（TJU） 11个nci支持的核心设施之一。由于x射线晶体学有潜力加强现有的nih资助的研究项目，并进一步发展TJU研究中心的研究，因此，杰斐逊医学院院长Tykocinski博士确定了x射线晶体学作为我们研究任务战略发展的技术之一。我们现有的两台x射线发生器已有11至22年的历史，限制了我们目前进行尖端结构工作的能力。旧的衍射仪（安装于1991年10月）

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