EMT/BSSE Synthetic Biological Integrated Circuits for Computing

EMT/BSSE 计算用合成生物集成电路

• 批准号: 1129098
• 负责人: Gregory Timp
• 金额: $ 19.91万
• 依托单位: University of Notre Dame
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1129098&HistoricalAwards=false
• 关键词: EMT; BSSE; Synthetic; Biological; Integrated

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.

EMT/BSSE：用于计算的合成生物综合电路，用于计算辅助合成生物学有望成为信息处理的新范式。 通过重新布线基因网络，可以选择细胞的分子生物学来生成用于计算的所有模块。此外，这些模块可以通过设计具有内置抗生素耐药性的电路来逐夜从单个细菌中廉价地廉价地生产。 但是，直到在不同单元格中运行的工程基因网络可以组装成集成电路以可靠地表达计算函数之前，综合生物学对信息处理的承诺将无法实现。 生物综合电路在解决方案上铰链铰链的前景：控制细胞的微环境，这会影响信号传递和时机；由于综合基因电路的响应时间很长，因此级联元素的难度；以及涉及少量分子的生化反应产生的随机噪声。 在这项研究中，研究人员合成了旨在高灵敏度和高信噪比蛋白质产生的基因回路，与它们转化细菌，然后使用分子信号将其汇合到大型阵列中，以将它们连接到大型阵列中，以将它们连接到大型阵列中，以表达复杂的计算功能。 研究人员使用定向进化来通过一系列基因回路进行对噪声的敏感性和稳定性进行分类。为了有效地生产具有高信噪比的蛋白质而没有过多能量的蛋白质，它们利用了使用MAZF（mRNA干扰酶）的方案，仅产生有关生存的大肠杆菌和其他阻止细胞生长的蛋白质。 一旦设计和测试了基因网络，使用光镊子将不同的细菌组装在水凝胶支架上，并将其亚微米精度组装成3D电路。