@article{90746,
  author = {Russell Gordley and Reid Williams and Caleb Bashor and Jared Toettcher and Shude Yan and Wendell Lim},
  title = {Engineering dynamical control of cell fate switching using synthetic phospho-regulons.},
  abstract = { Many cells can sense and respond to time-varying stimuli, selectively triggering changes in cell fate only in response to inputs of a particular duration or frequency. A common motif in dynamically controlled cells is a dual-timescale regulatory network: although long-term fate decisions are ultimately controlled by a slow-timescale switch (e.g., gene expression), input signals are first processed by a fast-timescale signaling layer, which is hypothesized to filter what dynamic information is efficiently relayed downstream. Directly testing the design principles of how dual-timescale circuits control dynamic sensing, however, has been challenging, because most synthetic biology methods have focused solely on rewiring transcriptional circuits, which operate at a single slow timescale. Here, we report the development of a modular approach for flexibly engineering phosphorylation circuits using designed phospho-regulon motifs. By then linking rapid phospho-feedback with slower downstream transcription-based bistable switches, we can construct synthetic dual-timescale circuits in yeast in which the triggering dynamics and the end-state properties of the ON state can be selectively tuned. These phospho-regulon tools thus open up the possibility to engineer cells with customized dynamical control. },
  year = {2016},
  journal = {Proc Natl Acad Sci U S A},
  volume = {113},
  pages = {13528-13533},
  month = {11/2016},
  issn = {1091-6490},
  doi = {10.1073/pnas.1610973113},
  language = {eng},
}