Effects of coupling strength and space on the dynamics of coupled toggle switches in stochastic gene networks with multiple-delayed reactions.
Effects of coupling strength and space on the dynamics of coupled toggle switches in stochastic gene networks with multiple-delayed reactions.
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耦合强度和空间对具有多重延迟反应的随机基因网络中耦合切换开关动力学的影响。
DOI：
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
A. Ribeiro
中科院分区：
文献类型：
--
作者：
A. Ribeiro
基因开关（TS）是研究最多的小基因调控网络（GRNs）之一，由于其简单和相关的作用。它们被解释为细胞分化中的决策电路，长期以来假设这一过程是可预测的，或者是细胞记忆单元。在这种情况下，它们必须是可靠的。一旦做出“决定”，系统必须保持稳定。获得稳定性的一种方法是通过复制TS的基因并将两个TS偶联。使用最近的建模策略的GRNs，驱动的延迟随机模拟算法（延迟SSA），允许建模转录和翻译作为multidelayed反应，我们分析耦合TS系统的稳定性。为此，我们引入耦合强度（C），一个参数来表征GRN结构，我们比较GRN稳定性（S）。我们首先表明，在转录的时间延迟，相关的启动子区域的释放，确保TS的双稳态，没有合作的结合或自激活反应。接下来，我们耦合两个TS并测量它们随C变化的切换频率。观察到三种动力学机制：（i）对于弱耦合，高频同步振荡，（ii）对于平均耦合，低频同步振荡，以及（iii）对于强耦合，系统在瞬态后变得稳定，处于两个稳态之一。在平均耦合区，随着C的增加，系统稳定性S经历一阶相变。之后，我们研究了两个耦合的TS，空间分离的动力学的两个隔间的空间分离的影响，其中空间分离建模为正态分布的随机时间延迟反应。随着C的增加，S的相变发生在较低的C值时，而不是当两个TS处于同一隔室中时。最后，我们耦合弱，均匀的几个TS在一个单一的隔间，并观察到，作为耦合TS的数量增加，系统通过相变在S，从振荡到稳定和C值低于前两种情况下。
Genetic toggle switches (TSs) are one of the best studied small gene regulatory networks (GRNs), due to their simplicity and relevant role. They have been interpreted as decision circuits in cell differentiation, a process long hypothesized to be bistable, or as cellular memory units. In these contexts, they must be reliable. Once a "decision" is made, the system must remain stable. One way to gain stability is by duplicating the genes of a TS and coupling the two TSs. Using a recent modeling strategy of GRNs, driven by a delayed stochastic simulation algorithm (delayed SSA) that allows modeling transcription and translation as multidelayed reactions, we analyze the stability of systems of coupled TSs. For this, we introduce the coupling strength (C), a parameter to characterize the GRN structure, against which we compare the GRN stability (S). We first show that time delays in transcription, associated to the promoter region release, ensure bistability of a TS, given no cooperative binding or self-activation reactions. Next, we couple two TSs and measure their toggling frequencies as C varies. Three dynamical regimes are observed: (i) for weak coupling, high frequency synchronized oscillations, (ii) for average coupling, low frequency synchronized oscillations, and (iii) for strong coupling the system becomes stable after a transient, in one of two steady states. The system stability, S, goes through a first order phase transition as C increases, in the average coupling regime. After, we study the effects of spatial separation in two compartments on the dynamics of two coupled TSs, where spatial separation is modeled as normally distributed random time delayed reactions. The phase transition of S, as C increases, occurs for lower values of C than when the two TSs are in the same compartment. Finally, we couple weakly and homogeneously several TSs within a single compartment and observe that as the number of coupled TSs increases, the system goes through the phase transition in S, from oscillatory to stable and for C values lower than in the two previous cases.
钙和 cAMP 信使系统在成骨细胞细胞内 pH 调节中的作用。
DOI：
10.1152/ajpcell.1992.262.1.c111
发表时间：
1992
期刊：
The American journal of physiology
影响因子：
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作者：
Green,J;Kleeman,CR
通讯作者：
Kleeman,CR
DOI：
10.1073/pnas.0503858102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Bratsun, D;Volfson, D;Hasty, J
通讯作者：
Hasty, J