Columbia University and Vanderbilt University, members of the National Institutes of Health’s Molecular Libraries Screening Center Network, last week submitted cell-based bioassay data to PubChem, the public online repository established by the NIH to share screening data generated by its Molecular Libraries and Imaging Initiative.
The bioassay protocols and data, which were submitted on July 12 and can be seen here, were enabled by assay instrumentation from GE Healthcare, Hamamatsu, and PerkinElmer, and demonstrate how instruments from those vendors can be applied to specific cell-based assays for small-molecule screening.
The data also show how detection instruments for cell-based assays in general are being used to generate a significant portion of data for PubChem by members of the MLSCN, further underscoring the significant market opportunity that exists within those institutions for instrumentation vendors.
Since the NIH established PubChem in September 2004 by providing a small organic molecule library, various government labs, academic institutions, and even commercial entities have submitted anything from additional small molecule structure and behavior profiles to biochemical and cell-based assay data generated using the small-molecule library.
That same year, the NIH founded the Chemical Genomics Center to jumpstart the formation the following year of the MLSCN, a network of nine academic or non-profit institutions, each of which was awarded three-year grants to develop screening methods to identify small molecules that can be used as molecular probes in biomedical research.
Other members of the MLSCN have already submitted data to PubChem, including the NCGC, the University of New Mexico, the University of Pittsburgh, the University of Pennsylvania, the San Diego Center for Chemical Genomics (via the Burnham Institute), and Emory University.
Data submitted by these institutions was obtained from both high-throughput cell-based and biochemical assays, and the majority of the data was obtained using non-imaging plate readers from Molecular Devices or PerkinElmer.
The University of New Mexico took a unique flow cytometry-based approach, while the NCGC has been one of the only institutes to employ a high-content screening approach by conducting a Redistribution assay using a TTP Labtech Acumen Explorer laser scanning cytometer.
Thus, the recent data from Columbia University is among the first to be obtained using high-content screening, and the first generated with an automated microscopy platform.
Specifically, the Columbia researchers, under principal investigator James Rothman, submitted data from a cellular assay for TNF-α-induced NFκB translocation in primary human umbilical vein endothelial cells. They used a GE Healthcare IN Cell Analyzer instrument and software to report nuclear-to-cytoplasmic ratio of p65 intensity as an index of translocation, cell count, and nuclear intensity.
The Vanderbilt researchers, meanwhile, under principal investigator David Weaver, submitted data from five different screening assays. Data from four of these assays — measurement of GPCR-mediated thallium flux through GIRK channels, a screen for agonists of the M4 muscarinic receptor, and screens for substrates and inhibitors of the voltage-dependent potassium channel beta subunit — were all obtained using a Hamamatsu FDSS 6000 kinetic plate reader.
The fifth assay, a relatively simple cytotoxicity assay, used a PerkinElmer Envision plate reader.
Public release of the data is particularly beneficial to Hamamatsu, which, despite having a strong life sciences play in its home country of Japan, has been slow to gain a foothold in Europe and the US. In those regions, Hamamatsu is better known as a supplier of high-end optical equipment such as lasers, cameras, and photomultiplier tubes.
Its FDSS drug screening system competes most directly with Molecular Devices’ FLIPR, which is widely regarded as the market leader in the US and Europe.