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This article is part of the supplement: Selected articles from The 5th IEEE International Conference on Systems Biology (ISB 2011)

Open Access Research

Time delay induced transition of gene switch and stochastic resonance in a genetic transcriptional regulatory model

Canjun Wang1*, Ming Yi23*, Keli Yang1 and Lijian Yang4

Author Affiliations

1 Nonlinear Research Institute, Baoji University of Arts and Sciences, Baoji 721016, China

2 Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China

3 National Center for Mathematics and Interdisciplinary Sciences, Chinese Academy of Sciences, Beijing 100190, China

4 Department of Physics and Institute of Biophysics, Huazhong Normal University, Wuhan 430071, China

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BMC Systems Biology 2012, 6(Suppl 1):S9  doi:10.1186/1752-0509-6-S1-S9

Published: 16 July 2012

Abstract

Background

Noise, nonlinear interactions, positive and negative feedbacks within signaling pathways, time delays, protein oligomerization, and crosstalk between different pathways are main characters in the regulatory of gene expression. However, only a single noise source or only delay time in the deterministic model is considered in the gene transcriptional regulatory system in previous researches. The combined effects of correlated noise and time delays on the gene regulatory model still remain not to be fully understood.

Results

The roles of time delay on gene switch and stochastic resonance are systematically explored based on a famous gene transcriptional regulatory model subject to correlated noise. Two cases, including linear time delay appearing in the degradation process (case I) and nonlinear time delay appearing in the synthesis process (case II) are considered, respectively. For case I: Our theoretical results show that time delay can induce gene switch, i.e., the TF-A monomer concentration shifts from the high concentration state to the low concentration state ("on""off"). With increasing the time delay, the transition from "on" to "off" state can be further accelerated. Moreover, it is found that the stochastic resonance can be enhanced by both the time delay and correlated noise intensity. However, the additive noise original from the synthesis rate restrains the stochastic resonance. It is also very interesting that a resonance bi-peaks structure appears under large additive noise intensity. The theoretical results by using small-delay time-approximation approach are consistent well with our numerical simulation. For case II: Our numerical simulation results show that time delay can also induce the gene switch, however different with case I, the TF-A monomer concentration shifts from the low concentration state to the high concentration state ("off""on"). With increasing time delay, the transition from "on" to "off" state can be further enhanced. Moreover, it is found that the stochastic resonance can be weaken by the time delay.

Conclusions

The stochastic delay dynamic approach can identify key physiological control parameters to which the behavior of special genetic regulatory systems is particularly sensitive. Such parameters might provide targets for pharmacological intervention. Thus, it would be highly interesting to investigate if similar experimental techniques could be used to bring out the delay-induced switch and stochastic resonance in the stochastic gene transcriptional regulatory process.