Negative autoregulation matches production and demand in synthetic transcriptional networks

Elisa Franco*, Giulia Giordano, Per Ola Forsberg, Richard M. Murray

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

34 Citations (Scopus)

Abstract

We propose a negative feedback architecture that regulates activity of artificial genes, or "genelets", to meet their output downstream demand, achieving robustness with respect to uncertain open-loop output production rates. In particular, we consider the case where the outputs of two genelets interact to form a single assembled product. We show with analysis and experiments that negative autoregulation matches the production and demand of the outputs: the magnitude of the regulatory signal is proportional to the "error" between the circuit output concentration and its actual demand. This two-device system is experimentally implemented using in vitro transcriptional networks, where reactions are systematically designed by optimizing nucleic acid sequences with publicly available software packages. We build a predictive ordinary differential equation (ODE) model that captures the dynamics of the system and can be used to numerically assess the scalability of this architecture to larger sets of interconnected genes. Finally, with numerical simulations we contrast our negative autoregulation scheme with a cross-activation architecture, which is less scalable and results in slower response times.

Original languageEnglish
Pages (from-to)589-599
Number of pages11
JournalACS Synthetic Biology
Volume3
Issue number8
DOIs
Publication statusPublished - 15 Aug 2014
Externally publishedYes

Keywords

  • in vitro
  • negative feedback
  • nucleic acid systems
  • synthetic biology
  • transcriptional circuits

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