Boosting functionality of synthetic DNA circuits with tailored deactivation

Nat Commun. 2016 Nov 15;7:13474. doi: 10.1038/ncomms13474.

Abstract

Molecular programming takes advantage of synthetic nucleic acid biochemistry to assemble networks of reactions, in vitro, with the double goal of better understanding cellular regulation and providing information-processing capabilities to man-made chemical systems. The function of molecular circuits is deeply related to their topological structure, but dynamical features (rate laws) also play a critical role. Here we introduce a mechanism to tune the nonlinearities associated with individual nodes of a synthetic network. This mechanism is based on programming deactivation laws using dedicated saturable pathways. We demonstrate this approach through the conversion of a single-node homoeostatic network into a bistable and reversible switch. Furthermore, we prove its generality by adding new functions to the library of reported man-made molecular devices: a system with three addressable bits of memory, and the first DNA-encoded excitable circuit. Specific saturable deactivation pathways thus greatly enrich the functional capability of a given circuit topology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • DNA / chemistry
  • DNA / genetics*
  • Feedback, Physiological*
  • Gene Regulatory Networks*
  • Models, Genetic*
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics

Substances

  • Oligonucleotides
  • DNA