Abstract for Gordon Conference:
Genetic manipulation is increasingly totted as the solution to the major challenges of our generation; combatting non-infectious diseases like cancer and heart disease through gene therapies, finding new sources of global energy through bio-synthetic microbes, or elucidating the basic principles of life by using transgenic discovery tools to perform experiments never before conceivable. It is especially true in this latter application that the control and rewiring of genetic elements has already revolutionized the way we do science. In each of these disciplines–medicine, engineering, and research–reliability is a central and critical theme. By this we mean that results of a manipulation are predictable, and they occur in clear reproducible ways. However, it is becoming increasingly clear that basic machinery of transcriptional control, which form the core of these approaches is intrinsically quite variable — that is to say, unreliable.
By counting transcriptional activation events among many individual cells simultaneously in a developing embryo we provide a sensitive measure of this variability. We use method to study a regulatory scheme used in natural developing systems which we show substantially reduces variations in gene expression. This scheme uses decoupled but simultaneously active enhancer sequences to ensure robust expression. Motivated by this discovery, we demonstrate that transgenic expression can also be made much more reliable by replicating this two enhancer regulatory mechanism — dramatically reducing noise in gene expression.