Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations
June 27-30, 2012
Marriott Copley Place
Andrea Califano, Columbia University, New York, NY
Stuart Schreiber, Broad Institute of MIT and Harvard, Cambridge, MA
Pamela A. Silver, Harvard Medical School, Boston, MA
Chemistry has provided an increasingly powerful repertoire of tools and techniques to interrogate biological systems. Today, we routinely use small-molecule probes to characterize differences in the response of cancer cells with distinct genetic backgrounds, to assemble synthetic biological systems capable of presenting unique phenotypic traits, and to modulate genetic and epigenetic cellular mechanisms in vitro and in vivo. For instance, efforts such as the Cancer Cell Line Encyclopedia (CCLE), Cancer Target Discovery and Development (CTD2), and the Library of Integrated Network-Based Cellular Signatures (LINCS) are only some of the major efforts in characterizing cellular response to small-molecule perturbation and chemically accessible cancer targets. Similarly, our ability to characterize the context-specific regulatory logic of the cell that mediates the link between a small-molecule perturbation and a phenotypic outcome has improved dramatically in the last five years. Now, for the first time, we have access to genome-wide regulatory models that can be interrogated to identify candidate genes, whose modulation using the tools of chemical biology may abrogate tumorigenesis, target key oncogene and non-oncogene addiction mechanisms, and rescue sensitivity to chemotherapy. Integration of these candidate genes with those emerging from small molecules or RNAi screens are now yielding a novel class of therapeutic targets for clinical development that could not have been gleaned by conventional approaches. This conference explored the intersection of the complementary disciplines of chemical biology and systems biology, the former generating large volumes of data from the application of chemical biology and molecular profiling approaches and the latter providing a rationale for data integration and knowledge synthesis using experimentally validated computational models of gene regulation. The program highlighted key areas of chemical systems biology, especially in the context of cancer, such as CTD2 and LINCS, as well as developments in synthetic biology at the interface of these disciplines.
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