Stability and robustness of unbalanced genetic toggle switches in the presence of scarce resources

Chentao Yong, Andras Gyorgy

Research output: Contribution to journalArticlepeer-review

Abstract

While the vision of synthetic biology is to create complex genetic systems in a rational fashion, system-level behaviors are often perplexing due to the context-dependent dynamics of modules. One major source of context-dependence emerges due to the limited availability of shared resources, coupling the behavior of disconnected components. Motivated by the ubiquitous role of toggle switches in genetic circuits ranging from controlling cell fate differentiation to optimizing cellular performance, here we reveal how their fundamental dynamic properties are affected by competition for scarce resources. Combining a mechanistic model with nullcline-based stability analysis and potential landscape-based robustness analysis, we uncover not only the detrimental impacts of resource competition, but also how the unbalancedness of the switch further exacerbates them. While in general both of these factors undermine the performance of the switch (by pushing the dynamics toward monostability and increased sensitivity to noise), we also demonstrate that some of the unwanted effects can be alleviated by strategically optimized resource competition. Our results provide explicit guidelines for the context-aware rational design of toggle switches to mitigate our reliance on lengthy and expensive trial-and-error processes, and can be seamlessly integrated into the computer-aided synthesis of complex genetic systems.

Original languageEnglish (US)
Article number271
JournalLife
Volume11
Issue number4
DOIs
StatePublished - Apr 2021

Keywords

  • Competition for shared resources
  • Modularity
  • Multistability
  • Potential landscape
  • Rational design
  • Robustness
  • Synthetic biology
  • Toggle switch

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology

Fingerprint Dive into the research topics of 'Stability and robustness of unbalanced genetic toggle switches in the presence of scarce resources'. Together they form a unique fingerprint.

Cite this