Revisiting a synthetic intracellular regulatory network that exhibits oscillations

  title={Revisiting a synthetic intracellular regulatory network that exhibits oscillations},
  author={Jonathan Tyler and Anne Shiu and Jay R Walton},
  journal={Journal of Mathematical Biology},
In 2000, Elowitz and Leibler introduced the repressilator—a synthetic gene circuit with three genes that cyclically repress transcription of the next gene—as well as a corresponding mathematical model. Experimental data and model simulations exhibited oscillations in the protein concentrations across generations. Müller et al. (J Math Biol 53(6):905–937, 2006) generalized the model to an arbitrary number of genes and analyzed the resulting dynamics. Their new model arose from five key… Expand
On three genetic repressilator topologies
All the novel mathematical models of three different repressilator topologies have simple dynamics that can be called regular behaviour: they have a single asymptotically stable steady state with small amplitude damping oscillations in the 3D case and no oscillation in one of the 6D cases and dampingscillation in the second 6D case. Expand
The effect of characteristic times on collective modes of two quorum sensing coupled identical ring oscillators
Abstract There has long been interest in methods to achieve variability of collective modes in systems of coupled identical oscillators. Extensive multistability and a dynamically rich parameterExpand
Comparison between Effects of Retroactivity and Resource Competition upon Change in Downstream Reporter Genes of Synthetic Genetic Circuits
It is shown that, in the dual-feedback oscillator, the level of the fluorescent protein reporter competing for degradation with the circuits’ components is important for the stability of the oscillations, suggesting retroactivity of reporters in this synthetic genetic oscillator. Expand
Efficient Framework Analysis for Targeted Drug Delivery Based on Internet of Bio-NanoThings
A framework analysis comprising of the compartmental model, for studying the effects and variances in drug concentration that occur inside intra-body nanonetworks through IoBNT, while taking into account the properties of target cells as well as the ligand-receptor binding mechanism is presented. Expand


Stochastic simulations of the repressilator circuit.
  • A. Loinger, O. Biham
  • Physics, Medicine
  • Physical review. E, Statistical, nonlinear, and soft matter physics
  • 2007
Stochastic analysis of the repressilator circuit is performed using the master equation and Monte Carlo simulations and it is found that fluctuations modify the range of conditions in which oscillations appear as well as their amplitude and period, compared to the deterministic equations. Expand
A generalized model of the repressilator
A detailed mathematical analysis of the dynamical behavior is provided for two model systems: a repressilator with leaky transcription and single-step cooperative repressor binding, and a repressive system with auto-activation and cooperative regulator binding. Expand
A synthetic oscillatory network of transcriptional regulators
This work used three transcriptional repressor systems that are not part of any natural biological clock to build an oscillating network, termed the repressilator, in Escherichia coli, which periodically induces the synthesis of green fluorescent protein as a readout of its state in individual cells. Expand
Dynamical properties of the repressilator model.
It is shown that oscillations arise from the existence of an absorbing toruslike region in the phase space of the model, and it is found that a pair of diffusively coupled repressilators displays synchronization properties similar to those of relaxation oscillators if the regulatory connections in the cyclic repression loop are strong. Expand
Transient dynamics around unstable periodic orbits in the generalized repressilator model.
It is shown that the family of unstable orbits possesses spatial symmetries and can also be understood in terms of traveling wave solutions of kink-like topological defects, and the long-lived oscillatory transients correspond to the propagation of quasistable two-kink configurations that unravel over a long time. Expand
Multi-stable dynamics of the non-adiabatic repressilator
The dynamics of the full idealized model of the paradigmatic genetic oscillator, the repressilator, is investigated using deterministic mathematical modelling and stochastic simulations and it is found that decreases in the TF binding rate changes the type of transition between steady state and oscillation. Expand
Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks
It is shown that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal, and this result holds independently of the regulatory functions used or number of genes. Expand
Synchronous long-term oscillations in a synthetic gene circuit
The first synthetic genetic oscillator, the repressilator, is revisited and modified using principles from stochastic chemistry in single cells to reduce error propagation and information losses, not by adding control loops, but by simply removing existing features. Expand
Protein sequestration versus Hill-type repression in circadian clock models.
The author discusses how a new class of models with protein sequestration-based repression differs dramatically from those based on Hill-type repression in several fundamental aspects: conditions for rhythm generation, robust network designs and the periods of coupled oscillators. Expand
Degradation of the Neurospora circadian clock protein FREQUENCY through the ubiquitin-proteasome pathway.
These results establish important roles for SCF(FWD-1) and CSN in the circadian clock of Neurospora and suggest that they are conserved components of the eukaryotic circadian clocks. Expand