(350e) Synergy In Cell Proliferation from Combinatorial Gene Expression

A common experiment is to over-express or inactivate a gene, and then observe the resulting phenotype. For example, researchers often over-express or inactivate a single proto-oncogene or tumor suppressor gene, and then record the frequency of tumors and the time it took for those tumors to develop. Yet it is generally understood that multiple genes are needed to transform a normal cell into a tumor cell. Secondly, these genes often synergize or cooperate, i.e., the genes acting alone have minimal effect, but together they cause a phenotypic change greater than the sum of their contributions. Furthermore, there is strong evidence that there are maximal levels of gene expression that drive cell immortalization and transformation?the highest expression of genes does not necessarily lead to the greatest phenotypic change. We are developing an experimental platform to evaluate a range of gene expression from combinations of genes in mammalian cells. To achieve this, we have borrowed from the metabolic engineer's toolkit, employing mutagenesis and inducible gene expression methods. Here we report the use of our gene expression platform to quantify synergy between genes in cell proliferation.