Current phenotypic High Throughput Screening (HTS) assays prove vital in discovering genotype-specific cancer drugs, but are limited to testing only one cell line at a time against a drug candidate. PRISM (Profiling Relative Inhibition Simultaneously in Mixture) is an efficient phenotypic HTS which pools 25 unique cancer lines together such that all 25 lines may be tested against a possible drug in a single assay well simultaneously. One possible limitation of this approach is that cell-cell communication may occur in the pooled format, causing cell lines to respond to compounds differently than they would in other pool combinations or when screened individually. We will investigate the role that cell-cell communication may play when pooling cell lines together by choosing 10 distinct mini-pools, containing five unique cell lines each, to screen against known drugs in 252 combinations of 25 cell lines each. By comparing any changes in a given cell line’s sensitivity to known drugs across all pool combinations, we will be able to determine if the pooling format is confounding sensitivity results. Cell lines that have significantly different sensitivities (>2 SD, P<0.05) in a given pool from their sensitivities in all other pools or against single cell line reference data will be noted as possible indicators of cell-cell communication and investigated further. This experiment will help optimize the assay via more informed pooling combinations or the omission of problematic cell lines, ultimately leading to an improved PRISM assay capable of discovering novel, genotype-specific cancer drugs more efficiently than current phenotypic HTS.
PROJECT: Pooled cell viability assays: Do neighboring cells influence drug sensitivity?
SRPG was an amazing way to learn a lot about my scientific interests, the research community here in Boston, and the tools for effectively communicating scientific research. Being able to work side by side with world leaders in genomics, in the unique environment that is the Broad, was invaluable in demystifying how cutting-edge translational research is done at the highest level. The professional and personal connections I made during this summer are invaluable, and I will continue to foster and benefit from them in the future. Simply put, SRPG not only opened many doors for me, but gave me the confidence to walk through them as well.