NIH Chemical Genomics Center

美国国立卫生研究院化学基因组中心

• 批准号: 8752454
• 负责人: John McKew
• 金额: $ 1444.9万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8752454
• 关键词: Address; Algorithms; Animal Testing; Applications Grants; Area; Asia; Award; Biological; Biological Assay; Biology; Books; Cell Line; Chemicals; Chemistry; Collaborations; Computer software; Country; Data; Deposition; Development; Disease; Environment; Europe; Extramural Activities; Foundations; Genes; Genome; Genomics; Goals; Grant; Health; Housing; Human; Human Genome Project; Individual; Informatics; Laboratories; Leadership; Legal patent; Manuals; Methods; Molecular Bank; Molecular Target; National Institute of Environmental Health Sciences; National Toxicology Program; Pathway interactions; Pharmaceutical Preparations; Phase; Phenotype; Production; Productivity; Proteins; Provider; PubChem; Publications; Publishing; RNA Interference; Rare Diseases; Reporting; Research; Research Personnel; Resources; Robotics; Running; Safety; Schedule; Science; Scientist; Site; Small Interfering RNA; System; Technology; Time; Toxic effect; Toxicology; Translating; Translational Research; United States Environmental Protection Agency; United States National Institutes of Health; Update; Validation; Visit; Work; assay development; base; cheminformatics; design; drug discovery; editorial; follow-up; high throughput screening; human disease; in vitro Assay; in vivo; insight; interest; member; new technology; novel; novel therapeutics; outreach; outreach program; programs; research study; response; screening; small molecule; statistics; technology development

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 34 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 18 projects, completing 12 pilot screens (1,000 genes), and completing 12 primary screens (7,000 22,000 genes), and moving into hit validation and follow-up on those projects. 13 new chemical probes of diverse biologies were discovered, and NCGC scientists published 56 publications during FY12. The NCGC filed 8 patent applications during this reporting period. Also during the reporting period, the NCGC deposited 243 BioAssays, 27 Summary AIDs, 13,143,171 concentration response curves, and a total of 52,572,684 data points into PubChem. NCGC continued to apply its chemistry expertise to optimizing probes; a portfolio of 19 in-house chemistry projects and 18 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 FY13, Tox21 continued its accelerated production phase. In the current reporting year, NCGC completed 12 full Tox21 screens and 13 smaller-scale screens and 20 follow-up experiments on specific, varied cell lines. In FY13, the Matrix Program, which takes a close look at phenotypic and combination screening for the discovery of novel drug pairs, prospered with several exciting projects. A total of 11 new projects were initiated, 5 of which have come to completion. This work could not have been feasible without the support of the NCI Major Opportunities Award, which was awarded to this program early on in FY13. The Assay Guidance manual has continued to evolve and has become a central resource for academic and industrial investigators interested in MLPCN science. In 2012, the manual was published as an eBook on the NLM/NCBI site (http://www.ncbi.nlm.nih.gov/books/NBK53196/). Since moving to the eBook format , the worldwide access statistics went from 7,099 hits in October 2012 to over 22, 094 hits in June 2013 with 10,695 unique IP addresses. This indicates , that a large number of new users are finding the Assay Guidance Manual site useful in early drug discovery and translational science applications. The manual remains a central resource for investigators interested in MLPCN science and several new chapters and revisions to the existing chapters have been added in 2013. The Book format also allows for dynamic real-time updates to the manual on a quarterly basis by expert content providers and the editorial group. 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. The NCGC's Outreach program continued its extraordinary record of productivity during the reporting period. NCGC staff advised 219 outside investigators on assay design and assay development, and assisted over 50 investigators with chemistry, informatics, and technology development inquiries. NCGC scientists gave 72 invited presentations throughout the U.S., Europe, and Asia during the period. NCGC outreach resulted in the submission of over 74 grant applications for NIH programs. The Assay Guidance manual has continued to evolve and has become a central resource for investigators interested in MLPCN science. During the reporting period, 73,967 visits were recorded, with 144,942 page views, and 54,504 unique visitors. 56% of these visitors originated from outside the US, from a total of 157 countries. 72% 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 currently has one project in progress. Finally, NCGC's work on its IATAP grants continued.

在报告年度，NCGC与全球300多名研究人员合作，就测定设计和开发，化学研究，信息学研究，技术开发项目以及运行高通量屏幕并化学优化小分子铅的建议。通过与分子库探测中心网络（MLPCN），美国环境保护署，国家毒理学计划，NIEHS，FDA，NCI，众多罕见疾病基础以及其他壁内和外部实验室，NCGC在34个高电平群体上进行分子和细胞靶标的NCGC筛查。 NCGC还继续在siRNA领域继续工作，对18个项目启动测定开发，完成了12个试点屏幕（1,000个基因），并完成了12个主要屏幕（7,000 22,000个基因），并在这些项目中进行了验证和随访。 13种新的化学探针发现了不同的生物学，NCGC科学家在2012财年发表了56个出版物。 NCGC在此报告期间提交了8项专利申请。同样在报告期间，NCGC沉积了243个生物测定，27个摘要艾滋病，13,143,171个浓度响应曲线，总计52,572,684个数据点到PubChem中。 NCGC继续将其化学专业知识应用于优化探针。全年维持了19个内部化学项目和18个化学合作的投资组合。在NCGC的领导下，以及美国环境保护署和NIEHS国家毒理学计划，21世纪项目（TOX21）的毒理学继续蓬勃发展。 TOX21是一项旨在预测化学物质对人类健康和环境的毒性的倡议。与当前动物测试相比，这是通过开发更多预测性，基于机理的方法来实现的，从而实现。 在2013财年期间，Tox21继续加速生产阶段。在当前的报告年度，NCGC完成了12个完整的TOX21屏幕和13个较小规模的屏幕，并在特定的各种细胞系上完成了20个随访实验。 在2013财年，矩阵计划仔细研究了表型和结合筛查，以发现新型毒品对，并随着几个激动人心的项目而繁荣发展。 总共启动了11个新项目，其中5个已经完成。 没有NCI大机会奖的支持，这项工作是不可行的，该奖项是在2013财年早期颁发给该计划的。 该测定指导手册一直在发展，并已成为对MLPCN科学感兴趣的学术和工业研究人员的中心资源。 2012年，该手册作为NLM/NCBI网站（http://www.ncbi.nlm.nih.gov/books/nbk53196/）上出版。 自从转向电子书格式以来，全球访问统计数据从2012年10月的7,099次命中量增加到2013年6月的094次命中，有10,695个唯一的IP地址。这表明，大量新用户正在发现对早期药物发现和转化科学应用有用的测定指导手册站点。该手册仍然是对MLPCN科学感兴趣的调查人员的中心资源，并在2013年添加了对现有章节的几个新章节和修订。该书籍格式还允许专家内容提供商和编辑集团通过季度对该手册进行动态实时更新。 鉴于NCGC的持续效率提高计划，我们能够通过项目团队和项目管理的驱动，通过改进应用程序，软件和利用时间表的改进来增加现有的机器人筛查，信息学和化学系统的吞吐量。在报告期间，NCGC维持其现有的机器人技术和生物安全水平1、2和3个设施。 NCGC的外展计划在报告期间继续其生产力的非凡记录。 NCGC的工作人员向219名外部调查人员提供了有关测定设计和测定开发的建议，并协助50多名研究人员进行了化学，信息学和技术开发查询。在此期间，NCGC科学家在美国，欧洲和亚洲进行了72个受邀演讲。 NCGC宣传导致提交了74多个NIH计划的赠款申请。该测定指南手册一直在发展，并已成为对MLPCN科学感兴趣的调查人员的中心资源。在报告期间，记录了73,967次访问，其中有144,942页的浏览量和54,504名唯一访问者。这些游客中有56％来自美国以外的157个国家。 72％的访问是新的访问，表明大量新用户正在找到《测定指导手册》。该手册仍然是对MLPCN科学感兴趣的调查人员的中心资源。在这一年中，NCGC还保持其作为NCI化学​​生物学财团的活跃成员的地位，目前正在进行一个项目。最后，NCGC在其IATAP赠款方面的工作仍在继续。