title: Programming a Pavlovian-like conditioning circuit in Escherichia coli.
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.
authors.affiliation: 1] Peking-Tsinghua Joint Centre for Life Sciences, Peking University, Beijing 100871, China [2] Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China [3] Centre for Quantitative Biology, Peking University, Beijing 100871, China [4].
authors.forename: Haoqian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1] Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China [2].
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Handuo
authors.initials: H
authors.lastname: Shi
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Weiyue
authors.initials: W
authors.lastname: Ji
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Longwen
authors.initials: L
authors.lastname: Huang
authors.affiliation: 1] Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China [2] Centre for Quantitative Biology, Peking University, Beijing 100871, China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Shen
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Rencheng
authors.initials: R
authors.lastname: Gao
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Shuke
authors.initials: S
authors.lastname: Wu
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Chengzhe
authors.initials: C
authors.lastname: Tian
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Siheng
authors.initials: S
authors.lastname: He
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Saw
authors.affiliation: Peking University Team for the International Genetically Engineered Machine Competition (iGEM), Peking University, Beijing 100871, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 1] Peking-Tsinghua Joint Centre for Life Sciences, Peking University, Beijing 100871, China [2] Centre for Quantitative Biology, Peking University, Beijing 100871, China [3] The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D053263:Gene Regulatory Networks; D008856:Microscopy, Fluorescence