Distributed biological computation with multicellular engineered networks
Distributed biological computation with multicellular engineered networks
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DOI：
10.1038/nature09679
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发表时间：
2011-01-13
期刊：
影响因子：
64.8
通讯作者：
Sole, Ricard
中科院分区：
文献类型：
--
作者：
Regot, Sergi;Macia, Javier;Sole, Ricard
在合成和系统生物学中正在进行的努力已经指向使用工程生物单元作为基本构建块（2，3）来构建人工计算设备（1）。这些努力受到电子电路标准设计（4-7）的启发，但受到通过适当连接将基本计算单元（逻辑门）布线所产生的困难的限制，每个单元由不同的分子实现。在这里，我们表明，有一个逻辑上不同的形式，实现复杂的布尔逻辑计算，减少布线的限制，由于所需的输出工程细胞之间的冗余分布。一个实际的实施是使用工程酵母细胞库，它可以以多种方式组合。每个结构定义了一个逻辑功能，结合细胞及其连接可以构建更复杂的合成设备。作为原理的证明，我们已经通过使用几个工程单元实现了许多逻辑功能。值得注意的是，这些单元的小修改和组合允许实现更复杂的电路，例如多路复用器或带有进位的1位加法器，这表明电路的小部分的再利用具有很大的潜力。我们的研究结果支持的方法，使用细胞财团作为一种有效的方式工程复杂的任务不容易解决使用单细胞实现。
Ongoing efforts within synthetic and systems biology have been directed towards the building of artificial computational devices(1) using engineered biological units as basic building blocks(2,3). Such efforts, inspired in the standard design of electronic circuits(4-7), are limited by the difficulties arising from wiring the basic computational units (logic gates) through the appropriate connections, each one to be implemented by a different molecule. Here, we show that there is a logically different form of implementing complex Boolean logic computations that reduces wiring constraints thanks to a redundant distribution of the desired output among engineered cells. A practical implementation is presented using a library of engineered yeast cells, which can be combined in multiple ways. Each construct defines a logic function and combining cells and their connections allow building more complex synthetic devices. As a proof of principle, we have implemented many logic functions by using just a few engineered cells. Of note, small modifications and combination of those cells allowed for implementing more complex circuits such as a multiplexer or a 1-bit adder with carry, showing the great potential for re-utilization of small parts of the circuit. Our results support the approach of using cellular consortia as an efficient way of engineering complex tasks not easily solvable using single-cell implementations.