Silver: Cell-Based Screens
We develop novel cell-based screens that take advantage of the spatial organization of mammalian cells. For example, many transcription factors are regulated at the level of their nuclear localization. The difference between nuclear and cytoplasmic location of a protein makes for a very robust microscopy-based high throughput screen. We have successfully employed such screens to look for small molecules that alter the nuclear location of key transcription factors involved in cancer. The ability to carry out such screens takes advantage of our close interactions with the Institute of Chemistry and Chemical Biology (ICCB). We have now extended cell-based screens to include searches for specific genes that alter protein and RNA location (Pablo Cironi, Natalie Gilks, Caleb Kenney). These screens use libraries of genes encoding certain protein families such as kinases, genome-wide siRNA libraries and highly engineered libraries derived from our Synthetic Biology efforts( See Section on Synthetic Biology). With these screens, we have begun to uncover new pathways that may lead to novel therapeutic targets and a better understanding and approach to drug development.