Multicellular computing using conjugation for wiring.

Multicellular computing using conjugation for wiring.
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DOI:
10.1371/journal.pone.0065986
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
de la Cruz F
de la Cruz F
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Goñi-Moreno A;Amos M;de la Cruz F

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合成生物学最近的努力集中在活细胞内逻辑功能的实现上。一个目的是促进细胞的内部“重新编程”和外部控制,在广泛的领域中具有潜在的应用。然而,对单细胞可以被重新设计的程度的基本限制已经导致了对多细胞系统的兴趣的增长,在多细胞系统中,“计算”以类似于现代计算机网络的方式分布在许多不同的细胞类型上。在这个模型中,单个细胞类型执行特定的子任务,然后将其结果传达给其他细胞类型进行进一步处理。因此,传达输出的方式对于此类计划的整体成功至关重要。以前在分布式细胞计算中的实验已经使用了全局通信方案,如群体感应(QS),以实现细胞类型之间的“布线”。虽然有用,但这种方法缺乏特异性,并且限制了在任何一个时间可以传输的信息量。我们提出了一种替代方案,基于特定的细胞-细胞结合。这种机制允许通过称为质粒的环状DNA链在细菌之间直接转移遗传信息。我们设计了一个多细胞的人口,能够计算,在一个分布式的方式,一个布尔XOR函数。通过这一点,我们描述了一个分布式逻辑的一般方案,其工作原理是在一个单一的人口混合不同的菌株,这构成了我们的新方法的一个重要优势。重要的是,通过接合交换的遗传信息的量显著高于通过基于QS的通信可能的量。我们提供完整的计算建模和模拟结果,使用确定性,随机性和空间显式方法。这些模拟探索一种可能的共轭有线蜂窝计算系统在不同条件下的行为,并为未来的实验室实现提供基线信息。
Recent efforts in synthetic biology have focussed on the implementation of logical functions within living cells. One aim is to facilitate both internal “re-programming” and external control of cells, with potential applications in a wide range of domains. However, fundamental limitations on the degree to which single cells may be re-engineered have led to a growth of interest in multicellular systems, in which a “computation” is distributed over a number of different cell types, in a manner analogous to modern computer networks. Within this model, individual cell type perform specific sub-tasks, the results of which are then communicated to other cell types for further processing. The manner in which outputs are communicated is therefore of great significance to the overall success of such a scheme. Previous experiments in distributed cellular computation have used global communication schemes, such as quorum sensing (QS), to implement the “wiring” between cell types. While useful, this method lacks specificity, and limits the amount of information that may be transferred at any one time. We propose an alternative scheme, based on specific cell-cell conjugation. This mechanism allows for the direct transfer of genetic information between bacteria, via circular DNA strands known as plasmids. We design a multi-cellular population that is able to compute, in a distributed fashion, a Boolean XOR function. Through this, we describe a general scheme for distributed logic that works by mixing different strains in a single population; this constitutes an important advantage of our novel approach. Importantly, the amount of genetic information exchanged through conjugation is significantly higher than the amount possible through QS-based communication. We provide full computational modelling and simulation results, using deterministic, stochastic and spatially-explicit methods. These simulations explore the behaviour of one possible conjugation-wired cellular computing system under different conditions, and provide baseline information for future laboratory implementations.
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