Role of functionality in two-component signal transduction: A stochastic study

Maity, Alok Kumar; Bandyopadhyay, Arnab; Chaudhury, Pinaki; Banik, Suman Kumar

doi:10.1103/physreve.89.032713

Cited by 13 publications

(12 citation statements)

References 44 publications

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“…This could be advantageous for the organism when the concentrations of the components varies from cell to cell. Thus all the cells would respond in the same way for a given input, and there would be no heterogeneity among the cells (19,20). Using a model of phosphotransfer kinetics in a bifunctional two-component system, Batchelor and Goulian (8) and Shinar et al (9) showed that the output of a TCS is directly proportional to the input signal.…”

Section: Discussionmentioning

confidence: 99%

Evidence of Robustness in a Two-Component System Using a Synthetic Circuit

et al. 2020

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Variation in the concentration of biological components is inescapable for any cell. Robustness in any biological circuit acts as a cushion against such variation and enables the cells to produce homogeneous output despite the fluctuation. The two-component system (TCS) with a bifunctional sensor kinase (that possesses both kinase and phosphatase activities) is proposed to be a robust circuit. Few theoretical models explain the robustness of a TCS, although the criteria and extent of robustness by these models differ. Here, we provide experimental evidence to validate the extent of the robustness of a TCS signaling pathway. We have designed a synthetic circuit in Escherichia coli using a representative TCS of Mycobacterium tuberculosis, MprAB, and monitored the in vivo output signal by systematically varying the concentration of either of the components or both. We observed that the output of the TCS is robust if the concentration of MprA is above a threshold value. This observation is further substantiated by two in vitro assays, in which we estimated the phosphorylated MprA pool or MprA-dependent transcription yield by varying either of the components of the TCS. This synthetic circuit could be used as a model system to analyze the relationship among different components of gene regulatory networks. IMPORTANCE Robustness in essential biological circuits is an important feature of the living organism. A few pieces of evidence support the existence of robustness in vivo in the two-component system (TCS) with a bifunctional sensor kinase (SK). The assays were done under physiological conditions in which the SK was much lower than the response regulator (RR). Here, using a synthetic circuit, we varied the concentrations of the SK and RR of a representative TCS to monitor output robustness in vivo. In vitro assays were also performed under conditions where the concentration of the SK was greater than that of the RR. Our results demonstrate the extent of output robustness in the TCS signaling pathway with respect to the concentrations of the two components.

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Section: Discussionmentioning

confidence: 99%

Evidence of Robustness in a Two-Component System Using a Synthetic Circuit

et al. 2020

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“…Several studies have shown that the concentration of R p in a bifunctional system is robust to variations in the concentration of the histidine kinase and the response regulator itself, when the response regulator is present in large excess compared to the kinase [27,28]. This property is not present in monofunctional systems [26].…”

Section: A Bacterial Two-component Systemmentioning

confidence: 99%

Uncertainty propagation for deterministic models of biochemical networks using moment equations and the extended Kalman filter

Kurdyaeva

Milias-Argeitis

2021

J. R. Soc. Interface.

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Differential equation models of biochemical networks are frequently associated with a large degree of uncertainty in parameters and/or initial conditions. However, estimating the impact of this uncertainty on model predictions via Monte Carlo simulation is computationally demanding. A more efficient approach could be to track a system of low-order statistical moments of the state. Unfortunately, when the underlying model is nonlinear, the system of moment equations is infinite-dimensional and cannot be solved without a moment closure approximation which may introduce bias in the moment dynamics. Here, we present a new method to study the time evolution of the desired moments for nonlinear systems with polynomial rate laws. Our approach is based on solving a system of low-order moment equations by substituting the higher-order moments with Monte Carlo-based estimates from a small number of simulations, and using an extended Kalman filter to counteract Monte Carlo noise. Our algorithm provides more accurate and robust results compared to traditional Monte Carlo and moment closure techniques, and we expect that it will be widely useful for the quantification of uncertainty in biochemical model predictions.

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“…The extended model has the same variables and parameters as the Cph8-OmpR model except the transition rates of histidine kinase. Here we focused on the state transition itself as a source of noise with saturating input [24]. Note that the ratio of transition rates v act to v ina (from inactive to active kinase state and vice versa) determines the active fraction of histidine kinase.…”

Section: Output Noise Attenuation In Fast Protein Activity Transitionmentioning

confidence: 99%

“…Although any transition of a component in a biological system inevitably generates noise with a frequency equal to that of the transition [24], this noise can be cancelled when such a component is in an upstream position in the a cascade and has a high-frequency transition. Cascade systems have a low-pass filter property through signal transduction [23,36] and can reduce the high-frequency noise generated in the upstream process.…”

Section: Output Noise Attenuation In Fast Protein Activity Transitionmentioning

confidence: 99%

High-frequency Noise Attenuation of a Two-component System Responding to Short-pulse Input

Nishida

Sekine

Kiga

et al. 2016

Proceedings of the 7th International Conference on Computational Systems-Biology and Bioinformatics

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Among the various biological devices developed and characterized in synthetic biology, light-sensing biological devices can serve as an input-output system owing to their light modulation property. The well-characterized devices in living systems are useful for modulating cellular sensing and transducing information. In this study, we examined short pulse responsiveness of a light-sensing two-component system (TCS), Cph8-OmpR, which was generated by replacing the sensor domain of the EnvZ-OmpR osmoregulatory system with the light sensor Cph1. We varied the input pulse width of the Cph8-OmpR system and found that an input width of <1 s was sufficient to alter the accumulation of a reporter gene upregulated by Cph8 phosphorylation of OmpR. Based on this result and the mathematical model showing that the timescale for the upstream Cph8-activity transition was much faster than that of downstream gene expression, we evaluated the merit of a TCS with such an unbalanced cascade. Our mathematical simulation of a cascade TCS suggests that high-frequency noise arising from fast transitions in kinase activity was attenuated throughout the cascade reaction. In terms of noise attenuation, these results can contribute to analyze biological cascade systems with the balance of reaction rates in each process.

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Role of functionality in two-component signal transduction: A stochastic study

Cited by 13 publications

References 44 publications

Evidence of Robustness in a Two-Component System Using a Synthetic Circuit

Evidence of Robustness in a Two-Component System Using a Synthetic Circuit

Uncertainty propagation for deterministic models of biochemical networks using moment equations and the extended Kalman filter

High-frequency Noise Attenuation of a Two-component System Responding to Short-pulse Input

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