Systematic design methodology for robust genetic transistors based on I-O specifications via promoter-RBS librariesReport as inadecuate




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BMC Systems Biology

, 7:109

Synthetic biology

Abstract

BackgroundSynthetic 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.

ResultsThree 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.

ConclusionThis 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.

KeywordsGenetic transistor Input-Output I-O characteristics Promoter-RBS library Systematic design methodology Design specifications Electronic supplementary materialThe online version of this article doi:10.1186-1752-0509-7-109 contains supplementary material, which is available to authorized users.

Yi-Ying Lee, Chih-Yuan Hsu contributed equally to this work.

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Author: Yi-Ying Lee - Chih-Yuan Hsu - Ling-Jiun Lin - Chih-Chun Chang - Hsiao-Chun Cheng - Tsung-Hsien Yeh - Rei-Hsing Hu - Che Li

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