NIH Chemical Genomics Center

在报告的一年中，NCGC与全球300多名研究人员合作，就分析设计和开发、化学研究、信息学研究、技术开发项目提供建议，并运行高通量筛选和化学优化小分子线索。NCGC与分子文库探针生产中心网络(MLPCN)、美国环境保护局、国家毒理学计划、NIEHS、FDA、NCI、众多罕见疾病基金会和其他校内外实验室合作，对几乎对生物学和疾病的每个领域都重要的分子靶标和细胞表型进行了40多次高通量筛选。NCGC还继续其在siRNA领域的工作，启动了13个项目的分析开发，完成了6个试点筛选(1,000个基因)，完成了3个初步筛选(7,000个基因)，并启动了另外2个项目，并进入了HIT验证和这些项目的后续工作。 在2011财年期间，发现了17种不同生物的新化学探针，NCGC科学家发表了49份出版物。在本报告所述期间，NCGC提交了6项专利申请。在本报告所述期间，NCGC还向PubChem存入了200个生物化验、49个艾滋病摘要、10,250,018条浓度反应曲线和总计47,202,574个数据点。NCGC继续将其化学专业知识应用于优化探针；全年保持了26个内部化学项目和5个化学合作项目的组合。 在NCGC的领导下，与美国环境保护局和NIEHS国家毒理学计划一起，21世纪的毒理学项目(Tox21)继续蓬勃发展。Tox21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使用的更具预测性的、基于机械的方法的体外分析来实现的。在2011财年，Tox21进入了更快的生产阶段。在本报告年度，NCGC在特定的、不同的细胞系上完成了12个完整的Tox21屏幕和1130个较小规模的屏幕。 由于NCGC的持续效率改进计划，我们能够通过在项目团队和项目管理的推动下，在应用程序、软件和使用调度方面的改进，增加现有机器人筛选、信息学和化学系统的吞吐量。在本报告所述期间，NCGC维持了现有的机器人技术和生物安全1、2和3级设施，此外还增加了专门用于Tox21筛查的新机器人系统。 在本报告所述期间，全国总工会的外联方案继续保持其非凡的生产力记录。NCGC的工作人员为229名外部调查人员提供了分析设计和测试开发方面的建议，并协助了50多名研究人员进行化学、信息学和技术开发方面的询问。在此期间，NCGC的科学家们在美国、欧洲和亚洲进行了73次应邀演讲。NCGC的推广活动导致提交了85多份NIH项目的拨款申请。 NCGC网站(ncgc.nih.gov)已完全重新设计，目前正处于修订的最后阶段，成为一个与TRND计划联合的新网站。NCGC网站上的分析指导手册继续发展，已成为对MLPCN科学感兴趣的调查人员的核心资源。为了让世界各地的科学家共享这一主题的信息，在2010财年期间设计并实施了Assay Wiki功能。在本报告所述期间，记录了25 020次访问，页面浏览量为52 421次，独立访问量为18 916次。这些游客中有55%来自美国以外，总共来自139个国家。76%的访问是新访问，这表明大量新用户正在查找分析指导手册网站。该手册仍然是对MLPCN科学感兴趣的调查人员的核心资源。 年内，NCGC还保持了其作为NCI化学生物学联盟活跃成员的地位，并开始了筛选项目的工作。NCGC开始了其诱导多能干细胞(IPS)捐赠的工作。此外，NCGC继续致力于其国家卫生研究院疟疾研究主任挑战奖。最后，NCGC关于其IATAP赠款的工作仍在继续。

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 40 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, initiating assay development on 13 projects, completing 6 pilot screens (1,000 genes), completing 3 primary screens (7,000 genes) and initiating 2 others, and moving into hit validation and follow-up on those projects. 17 new chemical probes of diverse biologies were discovered, and NCGC scientists published 49 publications during FY11. The NCGC filed 6 patent applications during this reporting period. Also during the reporting period, the NCGC deposited 200 BioAssays, 49 Summary AIDs, 10,250,018 concentration response curves, and a total of 47,202,574 data points into PubChem. NCGC continued to apply its chemistry expertise to optimizing probes; a portfolio of 26 in-house chemistry projects and 5 chemistry collaborations was maintained throughout 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. During FY11, Tox21 moved into its more accelerated production phase. In the current reporting year, NCGC completed 12 full Tox21 screens and 1130 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 Tox21 screening. The NCGC's Outreach program continued its extraordinary record of productivity during the reporting period. NCGC staff advised 229 outside investigators on assay design and assay development, and assisted over 50 investigators with chemistry, informatics, and technology development inquiries. NCGC scientists gave 73 invited presentations throughout the U.S., Europe, and Asia during the period. NCGC outreach resulted in the submission of over 85 grant applications for NIH programs. The NCGC website (ncgc.nih.gov) was completely redesigned and is in the final stages of revision into a new, joint website with the TRND program. 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, 25,020 visits were recorded, with 52,421 page views, and 18,916 unique visitors. 55% of these visitors originated from outside the US, from a total of 139 countries. 76% of visits were new visits, indicating that a large number of new users are finding the Assay Guidance Manual site. The manual remains a central resource for investigators interested in MLPCN science. During the year, the NCGC also maintained its status as an active member of the NCI's Chemical Biology Consortium and began work on screening projects. NCGC commenced work on its induced pluripotent stem (iPS) cell grant. In addition, NCGC continued to work on its NIH Directors Challenge Award for malaria research. Finally, NCGC's work on its IATAP grants continued.