噪声诱导多细胞系统的同步切换
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国家自然科学重点基金(60736028)和全国优秀博士学位论文(200521)资助项目.


Noise-induced Synchronized Switching of a Multicellular System
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This work was supported by a grant from The Natural Science Key Foundation of China (60736028), and The Special Foundation for National Distinguished Ph.D. Theses (200521).

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    摘要:

    在以往的工作中讨论了对单细胞的基因开关系统噪声如何诱导连贯切换.在此,对多细胞的基因开关网络系统研究各种噪声(包括细胞内噪声和细胞环境噪声)对同步切换的影响.发现:细胞内基因调控过程中的合成率和降解率的随机涨落以及细胞内的附加噪声均能够诱导群体基因开关系统的同步切换,而且存在一个最优的噪声强度,它使得这种同步切换的效果最佳.另一方面,细胞环境的随机涨落所导致的噪声(即环境噪声),不但能诱导上述同步切换,而且当细胞内噪声不足以诱导细胞群体的同步切换时,它通过压制内部噪声来达到增强群体系统的协作行为.最后,还分析了受噪声影响的信号分子的扩散率对细胞群体切换行为的影响.

    Abstract:

    Genetic bistable systems are a large class of important biological systems. Bistability, the capacity to achieve two distinct stable steady states in response to a set of external stimuli, arises within biological systems ranging from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. On the other hand, the increasing experimental evidence in the form of bimodal population distribution has indicated that noise plays a very key role in the switching of bistable systems. However, the physiological mechanism underling noise-induced switching behaviors has not been well explored yet. In the previous work, it has been showed that noise can induce coherent switch for a single genetic Toggle switch system. Here the influence of several kinds of noises (including intracellular and extracellular noises) on synchronized switch was investigated for a multicell gene toggle switch network system. It has been found that multiplicative noises resulting from fluctuations of either synthesis or degradation rates and the additive noise within each cell (they altogether are called as intracellular noises) all can induce the synchronized switch, and that there exists an optimal noise intensity such that the synchronized switch is optimally achieved and the amplification factor has the maximal value. On the other hand, the extracellular noises arising from the stochastic fluctuation of the cellular environment, not only brings about the synchronized switch, but also enhances it by suppressing intracellular fluctuations when the intracellular noises are not enough to induce the synchronized switch. Finally, the influence of the diffusive rate of signal molecules affected by noise on the dynamics of the multicellular system was also investigated, showing that the larger the diffusive rate, the better the synchronized switch and the larger the amplification factor.

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张家军,王军威,苑占江,周天寿.噪声诱导多细胞系统的同步切换[J].生物化学与生物物理进展,2008,35(8):929-939

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  • 收稿日期:2007-07-24
  • 最后修改日期:2008-05-19
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  • 在线发布日期: 2008-06-12
  • 出版日期: 2008-08-20