Computational characterization of recombinase circuits for periodic behaviors

Judith Landau, Christian Cuba Samaniego*, Giulia Giordano, Elisa Franco

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Recombinases are site-specific proteins found in nature that are capable of rearranging DNA. This function has made them promising gene editing tools in synthetic biology, as well as key elements in complex artificial gene circuits implementing Boolean logic. However, since DNA rearrangement is irreversible, it is still unclear how to use recombinases to build dynamic circuits like oscillators. In addition, this goal is challenging because a few molecules of recombinase are enough for promoter inversion, generating inherent stochasticity at low copy number. Here, we propose six different circuit designs for recombinase-based oscillators operating at a single copy number. We model them in a stochastic setting, leveraging the Gillespie algorithm for extensive simulations, and show that they can yield coherent periodic behaviors. Our results support the experimental realization of recombinase-based oscillators and, more generally, the use of recombinases to generate dynamic behaviors in synthetic biology.

Original languageEnglish
Article number105624
Number of pages22
JournaliScience
Volume26
Issue number1
DOIs
Publication statusPublished - 2023
Externally publishedYes

Keywords

  • Biocomputational method
  • Bioengineering
  • Synthetic biology

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