Designing synthetic regulatory networks capable of self-organizing cell polarization

Cell. 2012 Oct 12;151(2):320-32. doi: 10.1016/j.cell.2012.08.040. Epub 2012 Oct 4.


How cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computational model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feedback, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were significantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)). Circuits with combinatorial motifs yielded clear foci of synthetic PIP(3) that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Cell Polarity
  • Cytosol / metabolism
  • Feedback, Physiological
  • Models, Biological*
  • Phosphatidylinositol Phosphates / biosynthesis
  • Phosphatidylinositol Phosphates / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Synthetic Biology


  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 3,4,5-triphosphate