Biological signal processing with a genetic toggle switch.
Biological signal processing with a genetic toggle switch.
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DOI：
10.1371/journal.pone.0068345
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gerland U
中科院分区：
文献类型：
--
作者：
Hillenbrand P;Fritz G;Gerland U
复杂的基因调控需要的反应不仅取决于输入信号的当前水平，而且还取决于过去接收到的信号。在数字电子学中，具有这种特性的逻辑电路被称为时序逻辑，与没有这种内部存储器的简单组合逻辑相反。在分子生物学中，记忆以各种形式实现，例如蛋白质的生化修饰或多稳态基因电路，但处理输入信号和记忆内容的调节界面的设计通常不太清楚。在这里，我们探索设计约束这样的监管接口使用粗粒度的非线性模型和随机模拟详细的生化反应网络。我们测试了不同的设计，用于数字电子产品中最通用的存储元件JK锁存器的生物模拟。我们的分析表明，简单的蛋白质-蛋白质相互作用和蛋白质-DNA结合是足够的，在原则上，实现具有JK-闩锁的能力的遗传电路。然而，它也暴露了其可靠性的基本限制，这是由于生物信号处理是异步的，与大多数数字电子系统相比，它们具有中央时钟来协调所有操作的时序。我们描述了一个看似自然的方式来提高可靠性调用主从概念，从数字电子设计。这个概念可能有助于解释自然调节回路的设计，以及合成生物系统的设计。
Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, which processes the input signals and the memory content, is often not well understood. Here, we explore design constraints for such regulatory interfaces using coarse-grained nonlinear models and stochastic simulations of detailed biochemical reaction networks. We test different designs for biological analogs of the most versatile memory element in digital electronics, the JK-latch. Our analysis shows that simple protein-protein interactions and protein-DNA binding are sufficient, in principle, to implement genetic circuits with the capabilities of a JK-latch. However, it also exposes fundamental limitations to its reliability, due to the fact that biological signal processing is asynchronous, in contrast to most digital electronics systems that feature a central clock to orchestrate the timing of all operations. We describe a seemingly natural way to improve the reliability by invoking the master-slave concept from digital electronics design. This concept could be useful to interpret the design of natural regulatory circuits, and for the design of synthetic biological systems.
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影响因子：
9.9
作者：
Cox, Robert Sidney 3rd;Surette, Michael G;Elowitz, Michael B
通讯作者：
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影响因子：
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作者：
Gottesman, S;Roche, E;Sauer, RT
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DOI：
10.1016/s0378-4371(02)01038-5
发表时间：
2002-10-01
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0409553102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Buchler, NE;Gerland, U;Hwa, T
通讯作者：
Hwa, T