— In this paper, we analyze the oscillatory dynamics of a class of cyclic gene regulatory networks and provide engineering principles for the robust synthesis of biochemical oscillators. We first review the first author’s previous result that the oscillatory parameter regime of the gene regulatory circuits can be rigorously explored by the local stability analysis of a unique equilibrium. The local stability analysis then leads to the first engineering principle that the circuit components, or genes, should be chosen so that the kinetic profiles of the circuit components are similar to each other. Using a homogeneous oscillator model, we further discuss how to reduce the cellto-cell variability of the oscillators that is caused by intrinsic noise.
Yutaka Hori, Richard M. Murray