Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 47, Pages 13528-13533Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1610973113
Keywords
dynamical control; synthetic biology; phosphorylation
Categories
Funding
- Octave development community
- Ruth L. Kirschstein National Research Service Award
- University of California, San Francisco/Genentech Graduate Fellowship
- Cancer Research Institute Postdoctoral Fellowship
- Jane Coffin Childs Fund Postdoctoral Fellowship
- National Science Foundation Synthetic Biology and Engineering Research Center
- Howard Hughes Medical Institute
- National Institutes of Health [GM55040, GM62583, EY016546, GM081879]
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1330914] Funding Source: National Science Foundation
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available