Abstract

The repressilator is a genetic network that exhibits oscillations. The net-work is formed of three genes, each of which represses each other cyclically, creating a negative feedback loop with nonlinear interactions. In this work we present a computational bifurcation analysis of the mathematical model of the repressilator. We show that the steady state undergoes a transition from stable to unstable giving rise to a stable limit-cycle in a Hopf bifurcation. The nonlinear analysis involves a center manifold reduction on the six-dimensional system, which yields closed form expressions for the frequency and amplitude of the oscillation born at the Hopf. A parameter study then shows how the dynamics of the system are influenced for different parameter values and their associated biological significance.

Highlights

  • The repressilator is an artificial synthetic gene network created and named by Elowitz and Leibler [1]

  • We show that the steady state undergoes a transition from stable to unstable giving rise to a stable limit-cycle in a Hopf bifurcation

  • The biochemical details of the design principles for this oscillator are complicated, yet for the purposes of this work we present a brief background on the biology of the network: A gene undergoes a process called transcription, which consists in making a “copy” of the gene called messenger RNA

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Summary

Introduction

The repressilator is an artificial synthetic gene network created and named by Elowitz and Leibler [1]. The simplicity of the network’s structure and design makes the repressilator an ideal candidate for studies on the dynamic features of synthetic gene networks [2] [3]. The network exhibits negative feedback and nonlinear interactions, both of which are important features of dynamical systems exhibiting oscillations [4] [5] [6]. The biochemical details of the design principles for this oscillator are complicated, yet for the purposes of this work we present a brief background on the biology of the network: A gene undergoes a process called transcription, which consists in making a “copy” of the gene called messenger RNA (mRNA). Once mRNA is produced, it diffuses out of the nuc-

Verdugo DOI
Verdugo
Linear Stability Analysis of the Equilibrium Solution
Center Manifold Analysis
Unfolding the Center
Parameter Study
Continuation Analysis
Conclusions
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