Measurements of Gene Expression at Steady State Improve the Predictability of Part Assembly

ACS Synth Biol. 2016 Mar 18;5(3):269-73. doi: 10.1021/acssynbio.5b00156. Epub 2015 Dec 28.

Abstract

Mathematical modeling of genetic circuits generally assumes that gene expression is at steady state when measurements are performed. However, conventional methods of measurement do not necessarily guarantee that this assumption is satisfied. In this study, we reveal a bi-plateau mode of gene expression at the single-cell level in bacterial batch cultures. The first plateau is dynamically active, where gene expression is at steady state; the second plateau, however, is dynamically inactive. We further demonstrate that the predictability of assembled genetic circuits in the first plateau (steady state) is much higher than that in the second plateau where conventional measurements are often performed. By taking the nature of steady state into consideration, our method of measurement promises to directly capture the intrinsic property of biological parts/circuits regardless of circuit-host or circuit-environment interactions.

Keywords: batch culture; flow cytometry; gene expression; genetic circuits; predictable assembly; steady state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteria / genetics
  • Bacteria / growth & development
  • Bacteria / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Batch Cell Culture Techniques
  • Gene Expression
  • Gene Regulatory Networks
  • Models, Theoretical*
  • Plasmids / genetics
  • Plasmids / metabolism

Substances

  • Bacterial Proteins