Programming a Pavlovian-like conditioning circuit in Escherichia coli

Haoqian Zhang, Min Lin, Handuo Shi, Weiyue Ji, Longwen Huang, Xiaomeng Zhang, Shan Shen, Rencheng Gao, Shuke Wu, Chengzhe Tian, Zhenglin Yang, Guosheng Zhang, Siheng He, Hao Wang, Tiffany Saw, Yiwei Chen and Qi Ouyang ()
Additional contact information
Haoqian Zhang: Peking-Tsinghua Joint Centre for Life Sciences, Peking University
Min Lin: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Handuo Shi: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Weiyue Ji: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Longwen Huang: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Xiaomeng Zhang: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Shan Shen: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Rencheng Gao: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Shuke Wu: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Chengzhe Tian: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Zhenglin Yang: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Guosheng Zhang: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Siheng He: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Hao Wang: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Tiffany Saw: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Yiwei Chen: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University
Qi Ouyang: Peking-Tsinghua Joint Centre for Life Sciences, Peking University

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract Synthetic genetic circuits are programmed in living cells to perform predetermined cellular functions. However, designing higher-order genetic circuits for sophisticated cellular activities remains a substantial challenge. Here we program a genetic circuit that executes Pavlovian-like conditioning, an archetypical sequential-logic function, in Escherichia coli. The circuit design is first specified by the subfunctions that are necessary for the single simultaneous conditioning, and is further genetically implemented using four function modules. During this process, quantitative analysis is applied to the optimization of the modules and fine-tuning of the interconnections. Analogous to classical Pavlovian conditioning, the resultant circuit enables the cells to respond to a certain stimulus only after a conditioning process. We show that, although the conditioning is digital in single cells, a dynamically progressive conditioning process emerges at the population level. This circuit, together with its rational design strategy, is a key step towards the implementation of more sophisticated cellular computing.

Date: 2014
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DOI: 10.1038/ncomms4102

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