Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries

BMC Systems Biology

Bor-Sen Chen²  Zhen Xie³  Che Lin¹  Rei-Hsing Hu²  Tsung-Hsien Yeh²  Hsiao-Chun Cheng²  Chih-Chun Chang²  Ling-Jiun Lin²  Chih-Yuan Hsu²  Yi-Ying Lee⁴ 

[1] Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan;Lab of Genetic Circuit Design, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan;Center for Synthetic and Systems Biology, Bioinformatics Division, TNLIST, Tsinghua University, Beijing 100084, China;Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan

关键词: Design specifications;    Systematic design methodology;    Promoter-RBS library;    Input/Output (I/O) characteristics;    Genetic transistor;   

Others  :  1141970
DOI  :  10.1186/1752-0509-7-109

 received in 2013-06-04, accepted in 2013-10-17,  发布年份 2013

【 摘 要 】

Background

Synthetic genetic transistors are vital for signal amplification and switching in genetic circuits. However, it is still problematic to efficiently select the adequate promoters, Ribosome Binding Sides (RBSs) and inducer concentrations to construct a genetic transistor with the desired linear amplification or switching in the Input/Output (I/O) characteristics for practical applications.

Results

Three kinds of promoter-RBS libraries, i.e., a constitutive promoter-RBS library, a repressor-regulated promoter-RBS library and an activator-regulated promoter-RBS library, are constructed for systematic genetic circuit design using the identified kinetic strengths of their promoter-RBS components.

According to the dynamic model of genetic transistors, a design methodology for genetic transistors via a Genetic Algorithm (GA)-based searching algorithm is developed to search for a set of promoter-RBS components and adequate concentrations of inducers to achieve the prescribed I/O characteristics of a genetic transistor. Furthermore, according to design specifications for different types of genetic transistors, a look-up table is built for genetic transistor design, from which we could easily select an adequate set of promoter-RBS components and adequate concentrations of external inducers for a specific genetic transistor.

Conclusion

This systematic design method will reduce the time spent using trial-and-error methods in the experimental procedure for a genetic transistor with a desired I/O characteristic. We demonstrate the applicability of our design methodology to genetic transistors that have desirable linear amplification or switching by employing promoter-RBS library searching.

【 授权许可】

   
2013 Lee et al.; licensee BioMed Central Ltd.

【 图 表 】

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