Presentation: P02006

To push the boundaries of High Content Screening (HCS), significant advances in informatics tools and reagents are the two key components required. We demonstrate how to build 'systems cell biology' knowledge using a multiplexed HCS assay (cell cycle, apoptosis, histone H3 phosphorylation, and microtubule stability) to design a lead optimization strategy for natural product-derived, microtubule-targeted anticancer agents that exploits killing activity, while minimally perturbing the cell cycle regulation and microtubule stability. 'Heat Maps', based on KS statistics, rapidly identified trends in the data, 'Distribution Maps' demonstrated population average responses, and 'Cell Maps' made connections between cell constituents. To increase the power of multiplexed HCS, we describe a strategy focused on classes of reagents that 'measure and manipulate' specific cellular constituents: a random siRNA library to knock-down coding and non-coding RNA’s; multiplexed gene expression switches to up- and down-regulate multiple genes in the same cells; and fluorescence-based biosensors of specific protein activities.

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