Theory on the Dynamics of Oscillatory Loops in the Transcription Factor Networks

TL;DR

This paper presents a theoretical framework for designing robust and tunable transcription factor gene oscillators by coupling oscillators through logical interactions, revealing differences in stability and tunability between -OR- and -AND- type couplings.

Contribution

It introduces a detailed theoretical model for transcription factor oscillators and demonstrates how coupling strategies affect robustness and tunability of genetic oscillators.

Findings

-OR- type coupling provides period-buffering against perturbations.

-AND- type coupling allows tuning of oscillation period without amplitude loss.

Coupling strategies influence sensitivity and robustness of gene oscillators.

Abstract

We develop a detailed theoretical framework for various types of transcription factor gene oscillators. We further demonstrate that one can build genetic-oscillators which are tunable and robust against perturbations in the critical control parameters by coupling two or more independent Goodwin-Griffith oscillators through either -OR- or -AND- type logic. Most of the coupled oscillators constructed in the literature so far seem to be of -OR- type. When there are transient perturbations in one of the -OR- type coupled-oscillators, then the overall period of the system remains constant (period-buffering) whereas in case of -AND- type coupling the overall period of the system moves towards the perturbed oscillator. Though there is a period-buffering, the amplitudes of oscillators coupled through -OR- type logic are more sensitive to perturbations in the parameters associated with the promoter state dynamics than -AND- type. Further analysis shows that the period of -AND- type coupled dual-feedback oscillators can be tuned without conceding on the amplitudes. Using these results we derive the basic design principles governing the robust and tunable synthetic gene oscillators without compromising on their amplitudes.