Robust multicellular computing using genetically encoded NOR gates and chemical 'wires'.
Robust multicellular computing using genetically encoded NOR gates and chemical 'wires'.
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计算是将细胞组织成更高阶结构的基础，例如在生物膜中细菌的发育或空间关联期间。每个细胞执行一个简单的计算操作，但当与细胞间的通信相结合时，复杂的模式就会出现。在这里，我们通过将简单的遗传电路与群体感应相结合来研究这一过程，以在空间中产生更复杂的计算。我们通过排列两个串联启动子来构建大肠杆菌中的简单NOR逻辑门，这些启动子作为输入来驱动阻遏物的转录。阻遏物使作为输出的启动子失活。E.大肠杆菌携带相同的或非门，但输入和输出连接到不同的正交群体感应“发送器”和“接收器”设备。法人团分子构成了星门之间的线路。通过在不同的空间配置中排列菌落，产生了所有可能的双输入门，包括困难的XOR和EQUALS函数。该响应是强有力的和鲁棒的，在“开”和“关”状态之间具有5至>300倍的变化。这项工作有助于阐明设计规则，通过这些规则，简单的逻辑可以通过重新布线细胞之间的通信来产生多样化和复杂的计算。
Computation underlies the organization of cells into higher-order structures, for example during development or the spatial association of bacteria in a biofilm. Each cell performs a simple computational operation, but when combined with cell–cell communication, intricate patterns emerge. Here we study this process by combining a simple genetic circuit with quorum sensing to produce more complex computations in space. We construct a simple NOR logic gate in Escherichia coli by arranging two tandem promoters that function as inputs to drive the transcription of a repressor. The repressor inactivates a promoter that serves as the output. Individual colonies of E. coli carry the same NOR gate, but the inputs and outputs are wired to different orthogonal quorum-sensing ‘sender’ and ‘receiver’ devices. The quorum molecules form the wires between gates. By arranging the colonies in different spatial configurations, all possible two-input gates are produced, including the difficult XOR and EQUALS functions. The response is strong and robust, with 5- to >300-fold changes between the ‘on’ and ‘off’ states. This work helps elucidate the design rules by which simple logic can be harnessed to produce diverse and complex calculations by rewiring communication between cells.
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