title: Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Lee
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Hsu
authors.forename: Ling-Jiun
authors.initials: LJ
authors.lastname: Lin
authors.forename: Chih-Chun
authors.initials: CC
authors.lastname: Chang
authors.forename: Hsiao-Chun
authors.initials: HC
authors.lastname: Cheng
authors.forename: Tsung-Hsien
authors.initials: TH
authors.lastname: Yeh
authors.forename: Rei-Hsing
authors.initials: RH
authors.lastname: Hu
authors.forename: Che
authors.initials: C
authors.lastname: Lin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Lab of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan. bschen@ee.nthu.edu.tw.
authors.forename: Bor-Sen
authors.initials: BS
authors.lastname: Chen
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D008957:Models, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D049490:Systems Biology / Q000379:methods*