The NIH Chemical Genomics Center


NCGC

The NIH Chemical Genomics Center

Principal Investigator: Christopher Austin

The NIH Chemical Genomics Center (NCGC) is an ultrahigh-throughput screening and chemistry center that applies the tools of small molecule screening and discovery to develop chemical probes for the study of protein and cell functions. Using a process called quantitative high-throughput screening (qHTS), chemical libraries are screened at multiple concentrations (typically seven) to generate a concentration-response curve for each compound. qHTS comprehensively and efficiently characterizes biological activities of large chemical libraries to yield high quality datasets for chemical probe development and compound profiling. This process has been applied successfully to both cell-free and cell-based assays. Our Kalypsys robotic system uses multimodal detectors, the ViewLux and Envision systems, and a plate-based laser cytometry system, the Acumen Explorer, for high-capacity screening (100,000+ wells/day) in the reagent-sparing 1536-well plate format. The Center’s assay detection capabilities include absorbance, luminescence, FRET, TR-FRET, FP, FI, AlphaScreen�, as well as cell-based imaging assays that employ fluorescent proteins such as GFP. The NCGC also develops new paradigms for screening, informatics, and chemical probe development that extend the application of small molecule technology to new areas of the genome. The Center collaborates with pharmaceutical and biotechnology companies to produce public domain data, thereby allowing sharing of best practices to enable both chemical genomics and downstream drug development. The NCGC is also accepting chemical libraries from academic or industrial investigators, and encouraging library design and synthesis within the NCGC by visiting scientists. Using its qHTS process as little as 0.1 - 0.5 mg of compound will support several years of screening against numerous diverse biological systems. Libraries enter the NCGC archive for biological profiling as a 7-point titration covering a concentration range of nearly 5 orders of magnitude (typical concentrations in the biological assay begin at 100-30 uM and end at 3 to 1 nM). The NCGC is part of the intramural program of the National Human Genome Research Institute.

NCGC Capabilities and Technologies

Assay Formats Screening Capabilities Biologicial Expertise
Absorbance 1536-well compound titration-based primary screening Enzyme assays (kinase, phosphatase, protease, etc.)
AlphaScreen Biochemical Assay Screening Receptor functional assays
Fluorescence Cell-Based Assay Screening Protein-protein interaction assays
  • Fluorescence Intensity
High-Content Cell-Based laser cytometry Reconstituted enzyme cascades
  • Fluorescence Polarization
High Throughput Cell Imaging Metabolic enzyme systems
  • Time Resolved Fluorescence
  Redox enzyme systems
  • HTRF/LANCE (FRET)
  Assays relevant to rare genetic disorders
Luminescence   Understudied genes and gene families
Laser scanning cytometry (Acumen Explorer)   Cellular signaling pathways
Microscopy-based imaging (INCell 1000)   GFP-based assays
    Epigenetic mechanisms
    Compound profiling for ADMET and physiochemical properties
    RNA splicing assay
    Cell proliferation and cell death
    Cytotoxicity assays

For inquiries about assay development at a The NIH Chemical Genomics Center (NCGC), please contact the center representative listed in conjunction with visiting the Center’s Web site.

See also: Enabling PI-Center Collaboration Document

For further information about The NIH Chemical Genomics Center, see below: