Growth-rate-dependent dynamics of a bacterial genetic oscillator

TL;DR

This study investigates how bacterial growth rate influences the behavior of a genetic oscillator, revealing that growth conditions can switch the system between oscillatory and stable states, impacting synthetic biology applications.

Contribution

It demonstrates the coupling of bacterial growth rate with genetic oscillator dynamics, highlighting the importance of cellular physiology in circuit behavior.

Findings

Growth rate affects oscillation stability and period.

Circuit physical support influences oscillation dynamics.

Growth conditions can switch oscillations to fixed points.

Abstract

Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular "chassis" in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependences of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality.