NIH Chemical Genomics Center

在报告年度内，NCGC与全球300多名研究人员合作，就检测设计和开发、化学研究、信息学研究、技术开发项目提供建议，并进行高通量筛选和化学优化小分子先导化合物。 与分子库探针生产中心网络（MLPCN），美国环境保护署，国家毒理学计划，NIEHS，FDA，NCI，许多罕见疾病基金会以及其他内部和外部实验室合作，NCGC对几乎每个生物学和疾病领域都很重要的分子靶标和细胞表型进行了60多次高通量筛选。 NCGC还继续在siRNA领域开展工作，完成了2次全规模siRNA筛选活动，包括随访，3次初步筛选（7，000个基因）和6次中试筛选（1，000个基因）。 发现了20种不同生物的新化学探针，NCGC科学家在2010财年发表了43篇论文。 于本报告期内，NCGC获得3项专利。 同样在报告期内，NCGC将195项生物测定、38项汇总AID、7，734，000条浓度响应曲线和总计46，404，000个数据点存入PubChem。 NCGC继续运用其化学专业知识优化探针;年内实施了28个化学项目。 在NCGC的领导下，与美国环境保护署和NIEHS的国家毒理学计划沿着，21世纪毒理学项目（Tox 21）继续蓬勃发展。 Tox 21是一项旨在预测化学品对人类健康和环境的毒性的倡议。这是通过开发比目前动物试验所用方法更具预测性、基于机械的体外试验来实现的。2010年7月，FDA加入了合作; FDA将人类毒性数据与其他专业知识一起沿着项目，以改进当前的化学测试方法。 在本报告年度，NCGC完成了20个完整的Tox 21筛选和152个特定的不同细胞系的小规模筛选。 鉴于NCGC的持续效率改进计划，我们能够通过项目团队和项目管理部门推动的应用程序、软件和利用计划的改进，提高现有机器人筛选、信息学和化学系统的吞吐量。 NCGC在报告期内保持了现有的机器人技术和生物安全1级、2级和3级设施，并增加了一个专门用于RNAi筛查的新机器人系统。 在报告所述期间，NCGC的外展计划继续保持其非凡的生产力记录。NCGC工作人员为245名外部研究者提供了检测设计和检测开发方面的建议，并协助40多名研究者进行了化学、信息学和技术开发方面的调查。 NCGC的科学家们在美国各地做了104次受邀演讲，在此期间，欧洲和亚洲。 NCGC外联导致提交了60多份MLPCN项目的检测开发和筛选申请。 国家环境保护理事会网站（ncgc.nih.gov）得到维护，目前正在全面重新设计，以便纳入国家环境保护理事会/发展研究所网站。 NCGC网站上的检测指南手册不断发展，已成为对MLPCN科学感兴趣的研究者的核心资源。 为了让世界各地的科学家能够分享有关该主题的信息，在2010财年设计并实施了一项分析Wiki功能。 在本报告所述期间，该手册的点击次数为608 147次，访问者为48 437人。 其中47%的游客来自美国以外的125个国家。 点击次数表明，许多《检测指南手册》读者是重复访问者，他们发现该资源有助于经常重新访问。 年内，NCGC亦保持其作为NCI化学生物学联盟的活跃成员的地位。 此外，NCGC成功地争取到了专门用于诱导多能干细胞项目的NIH资金，该项目的工作已经开始。 国家疟疾理事会继续致力于其国家卫生研究院主任疟疾研究挑战奖。 最后，NCGCs的两项IATAP赠款的工作继续进行，并提交了更新;这两项IATAP资助包括一项修改非核苷逆转录酶抑制剂的计划，以将其效力范围扩展到新表征的RT突变体，以及一项修改天然产物甘露醇以抑制HIV RT的RNA酶结构域的计划。

During the reporting year, the NCGC worked with over 300 researchers worldwide to advise them on assay design and development, chemistry research, informatics research, technology development projects, and to run high-throughput screens and chemically optimize small molecule leads. In collaboration with the Molecular Libraries Probe Production Centers Network (MLPCN), the U.S. Environmental Protection Agency, the National Toxicology Program, NIEHS, FDA, NCI, numerous rare disease foundations, and other intramural and extramural laboratories, the NCGC performed over 60 high-throughput screens on molecular targets and cellular phenotypes important for virtually every area of biology and disease. The NCGC also continued its work in the field of siRNA, completing 2 full-scale siRNA screening campaigns including follow-up, 3 primary screens (7,000 genes), and 6 pilot screens (1,000 genes). 20 new chemical probes of diverse biologies were discovered, and NCGC scientists published 43 publications during FY10. The NCGC obtained 3 patents during this reporting period. Also during the reporting period, the NCGC deposited 195 BioAssays, 38 Summary AIDs, 7,734,000 concentration response curves, and a total of 46,404,000 data points into PubChem. NCGC continued to apply its chemistry expertise to optimizing probes; 28 chemistry projects were implemented during the year. Under leadership from NCGC, along with the U.S. Environmental Protection Agency and the National Toxicology Program of NIEHS, the Toxicology in the 21st Century project (Tox21) continued to flourish. Tox21 is an initiative designed to predict the toxicity of chemicals on human health and the environment. This is accomplished by developing in vitro assays for more predictive, mechanistically-based methods than those used with current animal testing. In July 2010, the FDA joined the collaboration; the FDA brings human toxicity data into the project, along with other expertise, to improve upon current chemical testing methods. In the current reporting year, NCGC completed 20 full Tox21 screens and 152 smaller-scale screens on specific, varied cell lines. Given the NCGC's continual efficiency improvement program, we were able to increase the throughput of existing robotic screening, informatics, and chemistry systems by improvements in applications, software, and utilization scheduling, driven by both the project teams and Project Management. The NCGC maintained its existing robotic technology and Bio Safety Levels 1, 2, and 3 facilities during the reporting period, in addition to adding a new robotic system dedicated to RNAi screening. The NCGC's Outreach program continued its extraordinary record of productivity during the reporting period. NCGC staff advised 245 outside investigators on assay design and assay development, and assisted over 40 investigators with chemistry, informatics, and technology development inquiries. NCGC scientists gave 104 invited presentations throughout the U.S., Europe, and Asia during the period. NCGC outreach resulted in the submission of over 60 assay development and screening applications for MLPCN programs. The NCGC website (ncgc.nih.gov) was maintained and is currently being completely redesigned, to be incorporated into an overall NCGC/TRND site. The Assay Guidance manual on the NCGC website has continued to evolve and has become a central resource for investigators interested in MLPCN science. To allow scientists across the world to share information on the topic, an Assay Wiki feature was designed and implemented during FY10. During the reporting period, the manual received 608,147 hits, with 48,437 unique visitors. 47% of these visitors originated from outside the US, from a total of 125 countries. The number of hits indicates that many Assay Guidance Manual readers are repeat visitors who find the resource useful to revisit on a frequent basis. During the year, the NCGC also maintained its status as an active member of the NCI's Chemical Biology Consortium. In addition, NCGC successfully competed for NIH funds dedicated to an induced pluripotent stem cell project, on which work has commenced. NCGC continued to work on its NIH Directors Challenge Award for malaria research. Finally, NCGCs work on its two IATAP grants continued and was submitted for renewal; the two IATAP awards include a program to modify non-nucleoside reverse transcriptase inhibitors to extend their potency range into newly characterized RT mutants, and a program to modify the natural product manicol to inhibit the RNAse domain of HIV RT.