Synchronization of synthetic gene oscillators

One of the defining characteristics of life is the ability to keep time, which organisms often achieve by using internal genetic ``clocks'' to govern fundamental cellular behavior. While the gene networks that produce oscillatory expression signals are typically quite elaborate, certain recurring network motifs are often found at the core of these biological clocks. In this lecture I will describe our recent experimental and theoretical work on the oscillatory dynamics of synthetic gene circuits. One common motif which leads to oscillations in many natural biological "clocks" is delayed auto-repression. We designed and constructed synthetic gene circuits based on this design principle, and observed robust and tunable oscillations of gene expression in bacteria. Computational modeling and theoretical analysis show that the key mechanism responsible for oscillations is a small delay in the negative feedback loop. In a strongly nonlinear regime, this time delay leads to long-period oscillations that are characterized by "degrade and fire'' dynamics. Using a variant of the same design in which oscillators are coupled chemical signals diffusing through cell membranes, we achieved regimes population-wide synchronization. We also predicted and observed an interesting phenomenon of intra-cellular synchronization of two different gene oscillators indirectly coupled by a common degradation enzyme.