Plug-and-Play Multicellular Circuits with Time-Dependent Dynamic Responses

ACS Synth Biol. 2018 Apr 20;7(4):1095-1104. doi: 10.1021/acssynbio.7b00463. Epub 2018 Apr 2.


Synthetic biology studies aim to develop cellular devices for biomedical applications. These devices, based on living instead of electronic or electromechanic technology, might provide alternative treatments for a wide range of diseases. However, the feasibility of these devices depends, in many cases, on complex genetic circuits that must fulfill physiological requirements. In this work, we explored the potential of multicellular architectures to act as an alternative to complex circuits for implementation of new devices. As a proof of concept, we developed specific circuits for insulin or glucagon production in response to different glucose levels. Here, we show that fundamental features, such as circuit's affinity or sensitivity, are dependent on the specific configuration of the multicellular consortia, providing a method for tuning these properties without genetic engineering. As an example, we have designed and built circuits with an incoherent feed-forward loop architecture (FFL) that can be easily adjusted to generate single pulse responses. Our results might serve as a blueprint for future development of cellular devices for glycemia regulation in diabetic patients.

Keywords: biological computation; diabetes; dynamic responses; multicellular circuits; synthetic biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Feedback, Physiological
  • Gene Regulatory Networks
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucose / metabolism*
  • Glucose Transport Proteins, Facilitative / genetics
  • Glucose Transport Proteins, Facilitative / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Insulin / genetics
  • Insulin / metabolism*
  • Mating Factor / genetics
  • Mating Factor / metabolism
  • Microorganisms, Genetically-Modified
  • Monosaccharide Transport Proteins / genetics
  • Promoter Regions, Genetic
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Signal Transduction
  • Synthetic Biology / methods*
  • Time Factors


  • Glucose Transport Proteins, Facilitative
  • HXT1 protein, S cerevisiae
  • Insulin
  • Monosaccharide Transport Proteins
  • Saccharomyces cerevisiae Proteins
  • alpha-factor (Saccharomyces cerevisiae)
  • Green Fluorescent Proteins
  • Mating Factor
  • Glucagon
  • Glucose