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.

Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2011
Total Cost
$18,338,903
Indirect Cost
Name
National Human Genome Research Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Cheng, Ken C-C; Inglese, James (2012) A coincidence reporter-gene system for high-throughput screening. Nat Methods 9:937
Boutin, Alisa; Allen, Michael D; Geras-Raaka, Elizabeth et al. (2011) Thyrotropin receptor stimulates internalization-independent persistent phosphoinositide signaling. Mol Pharmacol 80:240-6
Guha, Rajarshi; Dexheimer, Thomas S; Kestranek, Aimee N et al. (2011) Exploratory analysis of kinetic solubility measurements of a small molecule library. Bioorg Med Chem 19:4127-34
Hwang, Jong Yeon; Huang, Wenwei; Arnold, Leggy A et al. (2011) Methylsulfonylnitrobenzoates, a new class of irreversible inhibitors of the interaction of the thyroid hormone receptor and its obligate coactivators that functionally antagonizes thyroid hormone. J Biol Chem 286:11895-908
Dorjsuren, Dorjbal; Kim, Daemyung; Maloney, David J et al. (2011) Complementary non-radioactive assays for investigation of human flap endonuclease 1 activity. Nucleic Acids Res 39:e11
Ghoreschi, Kamran; Jesson, Michael I; Li, Xiong et al. (2011) Modulation of innate and adaptive immune responses by tofacitinib (CP-690,550). J Immunol 186:4234-43
Johnson, Ronald L; Hwang, Jong Yeon; Arnold, Leggy A et al. (2011) A quantitative high-throughput screen identifies novel inhibitors of the interaction of thyroid receptor beta with a peptide of steroid receptor coactivator 2. J Biomol Screen 16:618-27
Guha, Rajarshi (2011) The ups and downs of structure-activity landscapes. Methods Mol Biol 672:101-17
Yuan, Jing; Cheng, Ken Chih-Chien; Johnson, Ronald L et al. (2011) Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets. Science 333:724-9
Zhu, Wenge; Lee, Chrissie Y; Johnson, Ronald L et al. (2011) An image-based, high-throughput screening assay for molecules that induce excess DNA replication in human cancer cells. Mol Cancer Res 9:294-310

Showing the most recent 10 out of 89 publications