High-Content Screening and Profiling of Drug Activity in an Automated Centrosome-Duplication Assay.

@article{citeulike:1196, abstract = {Maintenance of centrosome number is essential for cell-cycle progression and genomic stability, but investigation of this regulation has been limited by assay difficulty. We present a fully automated image-based centrosome-duplication assay that is accurate and robust enough for both careful cell-biology studies and high-throughput screening, and employ this assay in a series of chemical-genetic studies. We observe that a simple cytometric profiling strategy, which is based on organelle size, groups compounds with similar mechanisms of action; this suggests a simple strategy for excluding compounds that undesirably target such activities as protein synthesis and microtubule dynamics. Screening a library of compounds of known activity, we found unexpected effects on centrosome duplication by a number of drugs, most notably isoform-specific protein kinase C inhibitors and retinoic acid receptor agonists. From a 16 320-member library of uncharacterized small molecules, we identified five potent centrosome-duplication inhibitors that do not target microtubule dynamics or protein synthesis. The analysis methodology reported here is directly relevant to studies of centrosome regulation in a variety of systems and is adaptable to a wide range of other biological problems.}, address = {Department of Systems Biology and Institute for Chemistry and Cell Biology, Harvard Medical School Boston, MA 02115, USA, Fax: (+1) 617-432-5012.}, author = {Perlman, Zachary E E. and Mitchison, Timothy J J. and Mayer, Thomas U U. }, citeulike-article-id = {1196}, doi = {http://dx.doi.org/10.1002/cbic.200400266}, issn = {1439-4227}, journal = {Chembiochem}, keywords = {assay, centrosome, drugdiscovery}, month = {November}, posted-at = {2006-05-28 17:32:27}, priority = {0}, title = {High-Content Screening and Profiling of Drug Activity in an Automated Centrosome-Duplication Assay.}, url = {http://dx.doi.org/10.1002/cbic.200400266}, year = {2004} }

TY - JOUR ID - citeulike:1196 L3 - citeulike-article-id:1196 N2 - Maintenance of centrosome number is essential for cell-cycle progression and genomic stability, but investigation of this regulation has been limited by assay difficulty. We present a fully automated image-based centrosome-duplication assay that is accurate and robust enough for both careful cell-biology studies and high-throughput screening, and employ this assay in a series of chemical-genetic studies. We observe that a simple cytometric profiling strategy, which is based on organelle size, groups compounds with similar mechanisms of action; this suggests a simple strategy for excluding compounds that undesirably target such activities as protein synthesis and microtubule dynamics. Screening a library of compounds of known activity, we found unexpected effects on centrosome duplication by a number of drugs, most notably isoform-specific protein kinase C inhibitors and retinoic acid receptor agonists. From a 16 320-member library of uncharacterized small molecules, we identified five potent centrosome-duplication inhibitors that do not target microtubule dynamics or protein synthesis. The analysis methodology reported here is directly relevant to studies of centrosome regulation in a variety of systems and is adaptable to a wide range of other biological problems. JF - Chembiochem SN - 1439-4227 AD - Department of Systems Biology and Institute for Chemistry and Cell Biology, Harvard Medical School Boston, MA 02115, USA, Fax: (+1) 617-432-5012. TI - High-Content Screening and Profiling of Drug Activity in an Automated Centrosome-Duplication Assay. KW - assay KW - centrosome KW - drugdiscovery AU - Perlman, Zachary E AU - Mitchison, Timothy J AU - Mayer, Thomas U PY - 2004/11/29/ UR - http://dx.doi.org/10.1002/cbic.200400266 ER -