Electronic Implementation of a Repressilator with Quorum Sensing Feedback

Hellen, Edward H.; Dana, Syamal K.; Zhurov, Boris; Volkov, E.I.

doi:10.1371/journal.pone.0062997

Cited by 18 publications

(26 citation statements)

References 20 publications

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“…The QS feedback is maintained by the autoinducer (AI) produced (rate k S1 ) by the protein B while the AI communicates with the external environment and activates (rate κ in combination with Michaelis function) production of mRNA for protein C, which, in turn, reduces the concentration of protein A resulting in activation of protein B production. In this way the protein B plays a dual role of direct inhibition of protein C synthesis and AI-dependent activation of protein C synthesis, resulting in complex dynamics of the repressilator, even for just a single repressilator [23].…”

Section: Numerical and Electrical Modelsmentioning

confidence: 99%

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Flexible dynamics of two quorum-sensing coupled repressilators

Hellen

Volkov

2017

Phys. Rev. E

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Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We investigate the dynamics of two identical synthetic genetic repressilators coupled by an additional plasmid which implements quorum sensing (QS) in each network thereby supporting global coupling. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, QS stimulates the transcriptional activity of chosen genes providing for competition between inhibitory and stimulatory activities localized in those genes. The "promoter strength", the Hill cooperativity coefficient of transcription repression, and the coupling strength, i.e., parameters controlling the basic rates of genetic reactions, were chosen for extensive bifurcation analysis. The results are presented as a map of dynamic regimes. We found that the remarkable multistability of the antiphase limit cycle and stable homogeneous and inhomogeneous steady states exists over broad ranges of control parameters. We studied the antiphase limit cycle stability and the evolution of irregular oscillatory regimes in the parameter areas where the antiphase cycle loses stability. In these regions we observed developing complex oscillations, collective chaos, and multistability between regular limit cycles and complex oscillations over uncommonly large intervals of coupling strength. QS coupling stimulates the appearance of intrachaotic periodic windows with spatially symmetric and asymmetric partial limit cycles which, in turn, change the type of chaos from a simple antiphase character into chaos composed of pieces of the trajectories having alternating polarity. The very rich dynamics discovered in the system of two identical simple ring oscillators may serve as a possible background for biological phenotypic diversification, as well as a stimulator to search for similar coupling in oscillator arrays in other areas of nature, e.g., in neurobiology, ecology, climatology, etc.

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Section: Numerical and Electrical Modelsmentioning

confidence: 99%

“…The hyperbolic dependence S/(1 + S) in Eq. (1c) is replaced in the circuit by the linear-piecewise-continuous behavior min(0.8S,1) as described previously [23]. Therefore Eq.…”

Section: Numerical and Electrical Modelsmentioning

confidence: 99%

Flexible dynamics of two quorum-sensing coupled repressilators

Hellen

Volkov

2017

Phys. Rev. E

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“…; Hellen et al . ; Ruocco & Fratalocchi ). Whether the period of the segmentation clock really affects the timing of the posterior shift of the G1/S transition window in zebrafish notochord remains to be elucidated.…”

Section: Uncovering Cell Cycle Dynamics With Quantitative Fucci Technmentioning

confidence: 99%

“…Since oscillating gene expression patterns have not been reported in notochordal cells and the stochastic window of the G1/S transition is always located posteriorly to the newly formed somites, there is a possibility that the G1/S transition is triggered by the periodic signals of the segmentation clock (Oates et al 2012;Benazeraf & Pourquie 2013). Several mathematical models have been successfully used to explain the period-doubling phenomena using nonlinear oscillatory systems (Mandelblat et al 2001;Jia et al 2012;Hellen et al 2013;Ruocco & Fratalocchi 2014). Whether the period of the segmentation clock really affects the timing of the posterior shift of the G1/ S transition window in zebrafish notochord remains to be elucidated.…”

Section: Uncovering Cell Cycle Dynamics With Quantitative Fucci Technmentioning

confidence: 99%

Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression

Saitou

Imamura

2015

Dev Growth Differ

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Cell cycle progression is strictly coordinated to ensure proper tissue growth, development, and regeneration of multicellular organisms. Spatiotemporal visualization of cell cycle phases directly helps us to obtain a deeper understanding of controlled, multicellular, cell cycle progression. The fluorescent ubiquitination-based cell cycle indicator (Fucci) system allows us to monitor, in living cells, the G1 and the S/G2/M phases of the cell cycle in red and green fluorescent colors, respectively. Since the discovery of Fucci technology, it has found numerous applications in the characterization of the timing of cell cycle phase transitions under diverse conditions and various biological processes. However, due to the complexity of cell cycle dynamics, understanding of specific patterns of cell cycle progression is still far from complete. In order to tackle this issue, quantitative approaches combined with mathematical modeling seem to be essential. Here, we review several studies that attempted to integrate Fucci technology and mathematical models to obtain quantitative information regarding cell cycle regulatory patterns. Focusing on the technological development of utilizing mathematics to retrieve meaningful information from the Fucci producing data, we discuss how the combined methods advance a quantitative understanding of cell cycle regulation.

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“…A feature shared by many organic systems, however, is the period doubling of their internal cycles. Appearing spontaneously or in response to external disturbances, the cycle of cellular organisms is observed to become more complex, enriching its activity and leading the system to complete its functionality with a period that is two times larger than initial one4567891011. This phenomenon is observed in a wide range of scales and can be found, for example, in the arrhythmia of cardiac functions4, or in the firing of neurons56, where it has been tentatively explained on the basis of the well know bifurcation to chaos paradigm910, or in the distribution of population growth in yeast12, where it was ascribed to genetic regulatory circuits.…”

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confidence: 99%

Period doubling induced by thermal noise amplification in genetic circuits

Ruocco

Fratalocchi

2014

Sci Rep

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Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an “elemental” genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise.

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Electronic Implementation of a Repressilator with Quorum Sensing Feedback

Cited by 18 publications

References 20 publications

Flexible dynamics of two quorum-sensing coupled repressilators

Flexible dynamics of two quorum-sensing coupled repressilators

Quantitative imaging with Fucci and mathematics to uncover temporal dynamics of cell cycle progression

Period doubling induced by thermal noise amplification in genetic circuits

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