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Sci. Signal., 15 May 2012
Vol. 5, Issue 224, p. rs4
Scaling Up Drug Discovery with Functional Genomics
The ability to perform high-throughput gain- and loss-of-function screens with mammalian cells in culture is a potentially important tool for exploring both basic cellular biology and drug discovery. Wood et al. describe a method they call "MicroSCALE screening," which overcomes several technical limitations and enables rapid, high-throughput screening of mammalian cells plated on patterned surfaces and infected with viral libraries to achieve overexpression of specific proteins or with RNA interference vectors to achieve protein knockdown. Their procedure overcomes issues related to cellular migration and lack of uniformity in cellular infection. In addition, the authors devised simple, inexpensive image-based screening methods that allow rapid data collection. With this MicroSCALE screening system, Wood et al. overexpressed a kinome library and identified proteins that influenced the sensitivity of melanoma cells to various clinically used antineoplastic agents. Thus, this method should advance drug discovery and enhance identification of effective combination therapies.
Citation: K. C. Wood, D. J. Konieczkowski, C. M. Johannessen, J. S. Boehm, P. Tamayo, O. B. Botvinnik, J. P. Mesirov, W. C. Hahn, D. E. Root, L. A. Garraway, D. M. Sabatini, MicroSCALE Screening Reveals Genetic Modifiers of Therapeutic Response in Melanoma. Sci. Signal.5, rs4 (2012).
Friedegund Meier and Annalisa M. VanHook (29 January 2013) Sci. Signal.6 (260), pc3.
[DOI: 10.1126/scisignal.2003968] |Abstract »|Full Text »|Podcast »
Daniela Beck, Heike Niessner, Keiran S. M. Smalley, Keith Flaherty, Kim H. T. Paraiso, Christian Busch, Tobias Sinnberg, Sophie Vasseur, Juan Lucio Iovanna, Stefan Drießen, Björn Stork, Sebastian Wesselborg, Martin Schaller, Tilo Biedermann, Jürgen Bauer, Konstantinos Lasithiotakis, Benjamin Weide, Jürgen Eberle, Birgit Schittek, Dirk Schadendorf, Claus Garbe, Dagmar Kulms, and Friedegund Meier (29 January 2013) Sci. Signal.6 (260), ra7.
[DOI: 10.1126/scisignal.2003057] |Editor's Summary »|Abstract »|Full Text »|PDF »|Supplementary Materials »