| ID | Title | Body | Facebook Description | Facebook image | Facebook Title | Facebook Video | Twitter Description | Twitter Image | Twitter Title | Meta tags |
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| 414 | Tox21 Assays | The following table lists the Tox21 assays currently available at NCATS. Review additional details about these assays.AssayAssay End Point*Cell TypeAssay ReadoutCell viabilityapoptosisIntracellular ATP,Caspase-3/7Hek293, Jurkat, HepG2, Sh-SY5Y, SK-N-SH, BJ, HUV-EC-C, MRC-5, mesangial, kidneyproximal tubules, N2a, H-4-II-E, NIH3T3LuminescenceMembrane integrityLDH release,Protease releaseHEK293, mesangialFluorescence,luminescenceMitochondrial toxicityMembrane potentialHepG2FluorescenceDNA damageMicronucleusCHOFluorescenceCytokineIL-8, TNF-αTHP-1Homogenoustime-resolved fluorescenceNuclear receptorAR, ERα, FXR, PPARδ, PPARγ, RXR, TRβ, VDR, GR, hPXR, AhR, rPXR, CAR, ERRHek293, HeLa, HepG2β-Lactamase reporter,luciferase reporterToxicity pathwayAP-1, HIF-1α, SIE, NF-κB, HSR, ESRE, ARE/Nrf2, CREB, p53, real-time cytotoxicity and viabilityME-180, HeLa, HepG2, Hek293, CHO, HCT-116, HepG2β-Lactamase reporter,luciferase reporterhERG channelThallium influxU-2OSFluorescenceG-protein-coupled receptor signalingTRHR, TSHRHek293Fluorescence, homogeneous time-resolved fluorescenceEnzyme activityAChESH-SY5YFluorescenceDevelopmental pathwayRetinol signaling, Hedgehog/Gli, SBE/SmadC3H10T1/2, 3T3, HEK 293TLuciferase reporter, fluorescence*AChE, acetylcholinesterase; AhR, aryl hydrocarbon receptor; AP-1, activator protein-1; AR, androgen receptor; ARE/Nrf2, antioxidant response element/NF-E2 related factor 2; CAR, constitutive androstane receptor; CREB, cAMP response element binding; ERα, estrogen receptor α; ERR, estrogen-related receptor; ESRE, endoplasmic reticulum stress response element; FXR, farnesoid X receptor; GR, glucocorticoid receptor; HIF-1α, hypoxia-inducible factor-1α; hPXR, human pregnane X receptor; HSR, heat shock response element; IL-8, interleukin-8; LDH, lactate dehydrogenase; NF-κB, nuclear factor kappa B; PPARδ, peroxisome proliferator-activated receptor δ; PPARγ, peroxisome proliferator-activated receptor γ; rPXR, rat pregnane X receptor; RXR, retinoid X receptor; SBE/Smad, Smad binding element; SIE, sis-inducible element; TNF-α, tumor necrosis factor α; TRβ, thyroid hormone receptor β; TRHR, thyrotropin-releasing hormone receptor; TSHR, thyroid-stimulating hormone receptor; VDR, vitamin D receptor. | ||||||||
| 413 | Tox21 Projects | Tox21 projects are made possible by new technologies and new discoveries in gene expression analysis, culture of human tissue stem cells and integrated pathway information.Cross-Partner ProjectsTo accommodate the expanded strategic direction and focus of the Tox21 collaboration, a central functional group called the cross-partner project was created in 2018.BioPlanetThrough this project, Tox21 researchers are working to annotate pathways by source, species, biological function/process, disease/toxicity relevance and availability of probing assays using data from the PubChem and ToxCast databases. The BioPlanet database currently hosts approximately 1,700 unique human pathways that have been thoroughly curated. A public web browser allows easy pathway visualization and analysis. Continued development of this resource will include compound activity data, sequence data, gene/protein expression data and pathway data from non-human species, in addition to organizing assays according to pathways/diseases/toxicity end points. This integrated platform will push forward systematic analysis and modeling of toxicity responses.AssaysTox21 researchers work on a variety of different assays:• Phenotypic readouts o Cytotoxicity assays (i.e., cell viability [measures ATP], kinetic measurement of cytotoxicity and viability in cells) o Apoptosis assays (i.e., caspase assays [measures activity of caspase 3/7, 8, 9]) o Membrane integrity assays (i.e., LDH and protease release) o Mitochondrial toxicity assays (i.e., mitochondrial membrane potential) o Gene toxicity assays • Differential cytotoxicity (DNA damage repair gene–deficient cell lines, DT40 and mouse cell lines) • ATADS (ELG1) • Micronucleus assay o Phospholipidosis assays o Genetic variation (more than 1,000 HapMap lines)• Pathway-specific toxicological mechanisms o Pathway assays using reporters (e.g., luciferase, β-lactamase) measuring hypoxia, ER stress, NF-κB*, p53*, ARE/Nrf2*, HSE, CREB, AP-1, STAT, NFAT, HIF-1α*, ESRE*, real time cytotoxicity and viability* o Developmental pathway assays (retinol signaling*, Hedgehog/Gli* and SBE/SMAD*)• Target-specific toxicological mechanisms o Nuclear receptor assays, including AR*, AhR*, ERα/β*, FXR*, GR*, LXR, PPARδ*, PPARγ*, PR*, PXR*, RXR*, TRβ*, VDR*, RORγ, CAR*, ERR* o G-protein-coupled receptor signaling assays, including TRHR* and TSHR* o Enzyme activity assays, including AChE* o hERG channel assay o Cytokine assays including IL-8 and TNF-α *Assays screened against the Tox21 10K library Neuronal ToxicityTox21 researchers are developing cellular models and methods to assess neurodegenerative and neurodevelopmental toxicities. Stem cell–derived, LUHMES-preserved and 3-D cultured neuronal models are included. Screening methods include neurite growth measurements and toxicant-chemical interaction “Toxmatrix” screening.ContactAnna Rossoshek | /sites/default/files/tox21_1260x630.jpg | Tox21 Projects | /sites/default/files/tox21_1260x630.jpg | Tox21 Projects | ||||
| 409 | Work with Tox21 | We are continually developing, validating and integrating toxicity assays into the quantitative high-throughput screening (qHTS) platform.Solicitation StatusTox21 currently is accepting assay proposals from investigators in all areas, both within and outside NIH and the federal government. Follow the instructions provided to nominate an assay.Nominate an AssayComplete one of the following forms, and email it to Menghang Xia, Ph.D.:NTP Tox21 Assay Nomination FormEPA Tox21 Assay Nomination FormProposed assays should be compatible with the qHTS guidelines in NCATS’ assay guidance criteria.Assay Evaluation and Development• NominationResearchers from academia, private institutions and government/non-government organizations may nominate assays.• ReviewThe Tox21 Assay Evaluation and Screening Group (with representatives from each of the Tox21 partners) reviews submitted assays on an ongoing basis. Tox21 leadership gives final approval. Assays are chosen based on their biological and toxicological relevance and adaptability to miniaturization and qHTS screening.• Optimization and MiniaturizationTox21 staff optimize and miniaturize selected assays into the qHTS screening platform.• Validation and ScreeningIn robotic online validation, the assay is screened in triplicate against a validation library. Tox21 experts evaluate validation data for reproducibility and positive control consistency before being submitted to the Assay Evaluation and Screening Group for approval.• Data Analysis and DisseminationTox21 staff analyze the resulting information and send raw data and/or summary tables to Tox21 partners regularly. All results are made publicly available. Other CollaborationsThe NCATS Tox21 team leads maintain partnerships with a variety of academics and private-sector parties, as well as other government organizations. Interested parties may contact Anna Rossoshek or individual team leads. | ||||||||
| 408 | Tox21 Scientific Capabilities | Tox21 experts carry out automated quantitative high-throughput screening using a library of approximately 10,000 compounds (Tox21 10K).This system is capable of weekly triplicate screening of the 10K library across 15 concentrations (1.2 nM to 92 µM). Other areas of expertise include development of human cell models using stem cells and 3-D cell culture, as well as genomics approaches, such as genome editing and high-throughput gene expression profiling. A dedicated informatics group performs chemi-informatics and bioinformatics analyses, including concentration-response and toxicological modeling.Within this format, the Tox21 program offers a variety of scientific capabilities available to NIH investigators and to other scientists whose assays have been submitted to and accepted by the program. Learn about the assay nomination and evaluation process. Tox21 ExpertiseTox21 experts have expertise in the following areas:Large-Scale Screening• Assay development• Assay design• Assay validation (assay screened in triplicate against pharmacologically active compounds and 88 additional compounds selected by the Tox21 Chemical Selection Working Group to evaluate reproducibility and positive control consistency)• Assay optimization• High-content screening• Quantitative high-throughput screening (qHTS)• Assay miniaturization (adapted for the qHTS platform)Genomic Analyses• Gene expression profiling (e.g., RNAseq and scRNAseq)• Epigenetic analysisHuman Cell Model Development• Stem cell–derived models of neurons, endothelium and cardiomyocytes• Immortalized cell line models of neurons, keratinocytes and renal proximal tubule epithelial cells• Genome engineering using CRISPRData Analysis• Normalization and correction• Concentration-response curve-fitting to generate potency and efficacy• Classification of curves based on significance of fit (by p-values), completeness of fit and efficacy• Reproducibility evaluation• Assignment of activity outcomes• Concentration-response point-of-departure determination from gene expression dataData DisseminationData available in these public databases encourage independent evaluations of Tox21 findings:• PubChem (National Library of Medicine)• Tox21 Data Browser (NCATS)• Chemical Effects in Biological Systems (National Toxicology Program)• Aggregated Computational Toxicology Resource (Environmental Protection Agency)Selected Publications• View a list of selected Tox21 publications. Tox21 ResourcesTox21’s scientific tools include robotic screening, assay development and informatics resources, all of which enable the program’s large-scale screening and data analysis efforts.Assays• Phenotypic readouts o Cytotoxicity assays (i.e., cell viability [measures ATP], kinetic measurement of cytotoxicity and viability in cells) o Apoptosis assays (i.e., caspase assays [measures activity of caspase 3/7, 8, 9]) o Membrane integrity assays (i.e., LDH and protease release) o Mitochondrial toxicity assays (i.e., mitochondrial membrane potential) o Gene toxicity assays Differential cytotoxicity (DNA damage repair gene–deficient cell lines, DT40 and mouse cell lines) ATADS (ELG1) Micronucleus assay o Phospholipidosis assays o Genetic variation (more than 1,000 HapMap lines)• Pathway-specific toxicological mechanisms o Pathway assays using reporters (e.g., luciferase, β-lactamase) measuring hypoxia, ER stress, NF-κB*, p53*, ARE/Nrf2*, HSE, CREB, AP-1, STAT, NFAT, HIF-1α*, ESRE*, real-time cytotoxicity and viability* o Developmental pathway assays (retinol signaling*, Hedgehog/Gli* and SBE/SMAD*)• Target-specific toxicological mechanisms o Nuclear receptor assays, including AR*, AhR*, ERα/β*, FXR*, GR*, LXR, PPARδ*, PPARγ*, PR*, PXR*, RXR*, TRβ*, VDR*, RORγ, CAR* and ERR* o G-protein-coupled receptor signaling assays, including TRHR* and TSHR* o Enzyme activity assays, including AChE* o hERG channel assay o Cytokine assays including IL-8 and TNFα*Assays screened against the Tox21 10K libraryGenomic Methods• Genomic engineering using CRISPR• Induced pluripotent stem cell culture and differentiation, including endothelial, cardiomyocyte and neuronal models• 3-D cell culture• High-throughput gene expression profiling (e.g., RNAseq)Informatics Tools• BioPlanet o Integrated pathway database that annotates molecular pathways by source, species, biological function/process, disease/toxicity relevance and availability of probing assays o Continued development of this platform includes compound activity data, sequence data, gene/protein expression data, pathways from non-human species and organization of assays according to pathways/diseases/toxicity end points o Allows easy browsing, visualization and analysis of the universe of pathways to facilitate systematic analysis and modeling of toxicity responses• Repository hosting all Tox21 qHTS data o Includes a graphic user interface for easy browsing and retrieval• Online system for tracking the status of all assays, protocols and experimental conditions o Includes a mechanism for generating standard laboratory protocols for each assay• Chemical browser hosting the Tox21 10K library compound structures and annotations, including analytical quality control results• Point-of-departure modeling of gene expression profiling dataRobotic PlatformThe Tox21 robot tests hundreds of thousands of chemicals against multiple in vitro assays to establish a signature of chemical compounds that can be used to predict in vivo human and rodent toxicity. This robust, automated platform uses plate readers, liquid handlers, incubators and a centrifuge to run a wide variety of biochemical and cell-based assays yielding reproducible, high-quality data.The screening system consists of a series of peripherals and workstations arranged around a central anthropomorphic robotic arm. The key components include the Kalypsys Director software, a pin tool device for nanoliter compound transfer, plate storage and environmentally controlled assay incubation units, nanoliter reagent dispensers (BioRAPTR, Multidrop, acoustic/noncontact), centrifuge (V-spin), and plate readers (ViewLux, EnVision and FDSS).This robotic system provides unparalleled speed, reliability and high-quality reproducible data. The millions of data points generated from robotic screening will be transformed into in vitro chemical signatures that may be used to study the mechanism of action of compounds, predict toxicity and minimize traditional animal toxicity testing. ContactAnna Rossoshek | ||||||||
| 405 | Tox21 Expertise | Tox21 experts have expertise in the following areas: Large-Scale Screening Assay development Assay design Assay validation (assay screened in triplicate against pharmacologically active compounds and 88 additional compounds selected by the Tox21 Chemical Selection Working Group to evaluate reproducibility and positive control consistency) Assay optimization High-content screening Quantitative high-throughput screening (qHTS) Assay miniaturization (adapted for the qHTS platform) Genomic Analyses Gene expression profiling (e.g., RNAseq and scRNAseq) Epigenetic analysis Human Cell Model Development Stem cell–derived models of neurons, endothelium and cardiomyocytes Immortalized cell line models of neurons, keratinocytes and renal proximal tubule epithelial cells Genome engineering using CRISPR Data Analysis Normalization and correction Concentration-response curve-fitting to generate potency and efficacy Classification of curves based on significance of fit (by p-values), completeness of fit and efficacy Reproducibility evaluation Assignment of activity outcomes Concentration-response point-of-departure determination from gene expression data Data Dissemination Data available in these public databases encourage independent evaluations of Tox21 findings: PubChem (National Library of Medicine) Tox21 Data Browser (NCATS) Chemical Effects in Biological Systems (National Toxicology Program) Aggregated Computational Toxicology Resource (Environmental Protection Agency) Selected Publications View a list of selected Tox21 publications. | ||||||||
| 404 | Licensing Opportunities | Looking for ways to collaborate and engage with NCATS? Each year, NCATS researchers develop many new inventions and technologies. Staff in the NCATS Office of Strategic Alliances create unique collaborations and licenses to transfer these inventions to interested partners for further research, development and commercialization. Learn more about the technologies and how to reach their Licensing Contact at the links below. Loading available technologies... Javascript must be enabled for the OTT-Embed Search Form to work. ottEmbedSettings = { // selector : '.ott-embed', // query : false, // facets: false, // facet1: false, facetType: false, // facet2: false, // facetDevStage: false, // facet3: false, // facetDiseaseArea: false, // facet4: false, // facetTechnology: false, // facet5: false, // facetCollaboration: false, // facet6: false, //// facetCenter: false, // facet7: false, // facetInventor: false, // facet8: false, // facet9: false, // facet10: false, sort: false, pager: false, // pager_top: false, // pager_bottom: false, // results: false, // filter: 'type:technology_bundle', filter: 'field_ics:NCATS', // filter: '"type:technology_bundle" AND "field_ics:NIEHS"', // template: '', hitsPerPage: 20, }; ott_embed(); .ott-embed .ais-RefinementList-count { margin-left: 8px; padding: 1px 8px; line-height: 1em; } .ott-embed .ais-RefinementList-list { margin: 0; padding: 0; list-style: none; line-height: 1em; width: 100%; } .ott-embed .search-results-container .facets-left-column { /* margin-right: 32px; */ width: 50%; max-width: 50%; } .ott-embed .ais-Hits-item .title>a { color: #0051a8; text-decoration: underline; font-weight: normal; } .ott-embed h2 { color: #0051a8; font-size: 14px; font-weight: bold; } NCATS' technology portfolio is currently under review and analysis. For further information please contact us at NCATSPartnerships@mail.nih.gov | ||||||||
| 403 | Forms & Model Agreements | Licensing Application and Agreements Used to when industry is interested in licensing a technology. Inter-Institutional Agreements Public Health Service License Agreements License Application Confidential Disclosure Agreements (CDAs) Used to exchange confidential information. NCATS Model 2-Way CDA (Word - 21KB) For two parties sharing confidential information. NCATS 1-Way Out CDA (Word - 24KB) For an outside party receiving confidential information from NIH. NCATS 1-Way In CDA (Word - 28KB) For an outside party providing confidential information to NIH. Cooperative Research and Development Agreements (CRADAs) Used when NIH and industry collaborate to further develop a technology for commercialization. Model NIH Materials CRADA (Word - 27KB) For collaborative studies of basic research. Model PHS CRADA (Word - 49KB) For collaborative studies of basic research. Intramural Clinical Trial CRADA (Word - 47KB) For collaborative studies that include a clinical trial conducted at NIH. Extramural Clinical Trial CRADA (Word - 49KB) For collaborative studies that include a clinical trial conducted at NIH-funded sites. Research Collaboration Agreement (RCA) Used in a collaborative project where confidential information and materials may be exchanging hands. RCA Template (Word - 31KB) Employee Invention Report Used when NCATS employees create new technologies. PHS Employee Discovery and Invention Report (Word - 113KB) Material Transfer Agreements (MTAs) Used to exchange research materials. NCATS Provider MTA (Word - 25KB) NCATS Recipient MTA (Word - 26KB) | ||||||||
| 401 | Tox21 Team | Systems Toxicology Team Lead: Menghang Xia, Ph.D. Staff Scientists: Srilatha Sakamuru, Ph.D. Caitlin Lynch, Ph.D. Research Scientist: Shu Yang, Ph.D. Biologists: Li Zhang Jean Zhao Postdoctoral Fellow: Masato Ooka, Ph.D. Genomic Toxicology Team Lead: David Gerhold, Ph.D. Staff: David Kuo Zhi-Bin Tong, Staff Scientist Computational Toxicology Team Lead: Ruili Huang, Ph.D. Staff: Deborah Ngan Tongan Zhao Research Fellow: Tuan Xu, Ph.D. Postdoctoral Fellow: Tsung-Jen Liao, Ph.D. | /sites/default/files/tox21_1260x630.jpg | Tox21 Team | /sites/default/files/tox21_1260x630.jpg | Tox21 Team | ||||
| 400 | Alliances at NCATS | The NCATS Office of Strategic Alliances aims to make it easy for industry and academia to interact and partner with NCATS laboratories and scientists to speed the translation of basic science knowledge into treatments for patients. The Strategic Alliances team provides a complete array of services to support NCATS technology development and partnership activities, including negotiation of standard forms and model agreements between NCATS and outside parties, such as universities and biopharmaceutical companies. These agreements provide for: The exchange of research materials under material transfer agreements (MTAs). Collaborative research conducted under cooperative research and development agreements (CRADAs). Clinical studies to determine the safety and efficacy of new agents under clinical trial agreements (CTAs). Exchange of confidential information under confidential disclosure agreements (CDAs). Informal collaborations that involve the transfer of materials and data under a Research Collaboration Agreement (RCA). The Strategic Alliances team reviews employee discovery and invention reports (EIRs), makes recommendations concerning filing of domestic and foreign patent applications, and manages licensing of all NCATS technologies. Inventions made by NCATS employees are owned by the federal government. Patenting and licensing are used to help ensure the technology is fully developed, commercialized and advancing public health. See all NCATS licensing opportunities. For information on other NIH technologies and to learn about other NIH programs, visit the NIH Office of Technology Transfer. Technology Transfer Education Overview of Technology Transfer: This slide presentation (PDF - 595KB) covers all you ever wanted to know but were afraid to ask about technology transfer. Video Tutorial: The Federal Laboratory Consortium for Technology Transfer (FLC) offers a free video tutorial on technology transfer, including an overview of the topic, considerations for federal agencies, different mechanisms for technology transfer and the role of the FLC. Advanced Studies in Technology Transfer: To learn more about technology transfer or to complete the Advanced Studies in Technology Transfer certificate program offered by the Foundation for Advanced Education in the Sciences (FAES), visit the FAES website. Training in Technology Transfer: Technology transfer is a growing field that encompasses scientific research, innovation, and commercialization. To learn more about this field, and training and development opportunities, visit the National Cancer Institute’s Technology Transfer Center website. | ||||||||
| 398 | Tox21 Scientific Capabilities | Tox21 experts carry out automated quantitative high-throughput screening using a library of approximately 10,000 compounds (Tox21 10K). This system is capable of weekly triplicate screening of the 10K library across 15 concentrations (1.2 nM to 92 µM). Other areas of expertise include development of human cell models using stem cells and 3-D cell culture as well as genomics approaches, such as genome editing and high-throughput gene expression profiling. A dedicated informatics group performs chemi-informatics and bioinformatics analyses, including concentration-response and toxicological modeling. Within this format, the Tox21 program offers a variety of scientific capabilities available to NIH investigators as well as other scientists whose assays have been submitted to and accepted by the program. Learn about the assay nomination and evaluation process. Learn more about the Tox21 program’s available resources and expertise. | /sites/default/files/tox21_1260x630.jpg | Tox21 Scientific Capabilities | /sites/default/files/tox21_1260x630.jpg | Tox21 Scientific Capabilities |
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