Harnessing the central dogma for stringent multi-level control of gene expression

Filomena V Greco, Amir Pandi, Tobias J. Erb, Claire S Grierson, Thomas E Gorochowski*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Strictly controlled inducible gene expression is crucial when engineering biological systems where even tiny amounts of a protein have a large impact on function or host cell viability. In these cases, leaky protein production must be avoided, but without affecting the achievable range of expression. Here, we demonstrate how the central dogma offers a simple solution to this challenge. By simultaneously regulating transcription and translation, we show how basal expression of an inducible system can be reduced, with little impact on the maximum expression rate. Using this approach, we create several stringent expression systems displaying >1000-fold change in their output after induction and show how multi-level regulation can suppress transcriptional noise and create digital-like switches between ‘on’ and ‘off’ states. These tools will aid those working with toxic genes or requiring precise regulation and propagation of cellular signals and illustrate the value of more diverse regulatory designs for synthetic biology.
Original languageEnglish
JournalNature Communications
DOIs
Publication statusPublished - 19 Mar 2021

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

Keywords

  • gene expression
  • transcription
  • translation
  • genetic circuit
  • synthetic biology
  • regulatory motif
  • feed forward loop
  • control

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