Designing synthetic regulatory networks capable of self-organizing cell polarization

Angela H. Chau, Jessica M. Walter, Jaline Li Gerardin, Chao Tang*, Wendell A. Lim

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

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 (PIP3). 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.

Original languageEnglish (US)
Pages (from-to)320-332
Number of pages13
JournalCell
Volume151
Issue number2
DOIs
StatePublished - Oct 12 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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