Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies

Published on May 10, 2019in Science41.04
· DOI :10.1126/science.aau8287
Caleb J. Bashor6
Estimated H-index: 6
(Rice University),
Caleb J. Bashor1
Estimated H-index: 1
(Rice University)
+ 4 AuthorsAhmad S. Khalil18
Estimated H-index: 18
(Wyss Institute for Biologically Inspired Engineering)
Eukaryotic genes are regulated by multivalent transcription factor complexes. Through cooperative self-assembly, these complexes perform nonlinear regulatory operations involved in cellular decision-making and signal processing. In this study, we apply this design principle to synthetic networks, testing whether engineered cooperative assemblies can program nonlinear gene circuit behavior in yeast. Using a model-guided approach, we show that specifying the strength and number of assembly subunits enables predictive tuning between linear and nonlinear regulatory responses for single- and multi-input circuits. We demonstrate that assemblies can be adjusted to control circuit dynamics. We harness this capability to engineer circuits that perform dynamic filtering, enabling frequency-dependent decoding in cell populations. Programmable cooperative assembly provides a versatile way to tune the nonlinearity of network connections, markedly expanding the engineerable behaviors available to synthetic circuits.
  • References (54)
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