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• W2002189052 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 (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." @default.
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• W2002189052 date "2012-10-01" @default.
• W2002189052 modified "2023-10-16" @default.
• W2002189052 title "Designing Synthetic Regulatory Networks Capable of Self-Organizing Cell Polarization" @default.
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• W2002189052 doi "https://doi.org/10.1016/j.cell.2012.08.040" @default.
• W2002189052 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3498761" @default.
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