EMT/BSSE Synthetic Biological Integrated Circuits for Computing

EMT/BSSE：合成生物学集成电路计算摘要合成生物学有望为信息处理提供新的范例。 通过重新连接基因网络，细胞的分子生物学可以被用来产生用于计算的所有模块。此外，通过设计具有内置抗生素抗性的电路，这些模块可以在一夜之间从单个细菌中廉价地大量生产。 但是合成生物学对信息处理的承诺获胜了吗？直到在不同细胞中操作的工程基因网络可以组装成集成电路以可靠地表达计算功能，才能实现。 生物集成电路的前景取决于三个问题的解决方案：对细胞微环境的控制，这会影响信号传输和定时;由于合成基因电路中明显的响应时间长，级联元件的困难;以及涉及少量分子的生化反应产生的随机噪音。 在这项研究中，研究人员合成了为高灵敏度和高信噪比蛋白质生产而设计的基因电路，用它们转化细菌，然后使用分子信号将不同的细菌以亚微米精度组装成大阵列，将它们连接在一起以表达复杂的计算功能。 研究人员使用定向进化对一系列基因电路进行排序，以追求对噪声的敏感性和稳定性。为了有效地生产具有高信噪比的蛋白质而不需要过多的能量，他们利用了一种使用MazF（一种mRNA干扰酶）的方案，只生产活E.大肠杆菌，否则会抑制细胞生长。 一旦基因网络被设计和测试，不同的细菌就被组装在水凝胶支架上，使用光镊以亚微米精度组装成3D电路。

EMT/BSSE: Synthetic Biological Integrated Circuits for ComputingAbstractSynthetic biology promises a new paradigm for information processing. By rewiring gene networks, the molecular biology of the cell can be co-opted to produce all the modules used for computation. Moreover, these modules can be produced in very large numbers inexpensively from a single bacterium literally overnight by designing circuits with built-in antibiotic resistance. But the promise of synthetic biology for information processing won?t be realized until engineered gene networks operating in different cells can be assembled into integrated circuits to reliably express a computing function. The prospects for a biological integrated circuit hinge on solutions to three problems: control over the microenvironment of the cell, which affects signal transmission and timing; the difficulty of cascading elements due to the long response time evident in the synthesized gene circuits; and the stochastic noise that develops from biochemical reactions involving a small number of molecules. In this research, the investigators synthesize gene circuits designed for high sensitivity and high signal-to-noise protein production, transform bacteria with them, and then assemble the different bacteria with submicron precision into large arrays using molecular signals to wire them together to express a complex computing function. The researchers sort through a succession of gene circuits using directed evolution in pursuit of sensitivity and stability with respect to noise. To efficiently produce proteins with high signal-to-noise ratio without excessive energy, they leverage a protocol that uses MazF, an mRNA interferase, to produce only the proteins of interest in living E. coli and otherwise arrest cell growth. Once the gene networks are designed and tested, the different bacteria are assembled on a hydrogel scaffold with submicron precision into 3D circuits using optical tweezers.