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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)
Abstract
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)
  • Citations (2)
References54
Newest
#1Delphine Aymoz (UNIL: University of Lausanne)H-Index: 3
#2Carme Solé (UPF: Pompeu Fabra University)H-Index: 15
Last.Serge Pelet (UNIL: University of Lausanne)H-Index: 17
view all 7 authors...
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#2James M. Linton (California Institute of Technology)H-Index: 3
Last.Michael B. Elowitz (California Institute of Technology)H-Index: 47
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#2Krishna Shrinivas (MIT: Massachusetts Institute of Technology)H-Index: 3
Last.Phillip A. Sharp (MIT: Massachusetts Institute of Technology)H-Index: 135
view all 5 authors...
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Last.Jeremy Gunawardena (Harvard University)H-Index: 28
view all 4 authors...
#1Amir Mitchell (UCSF: University of California, San Francisco)H-Index: 7
#2Ping Wei (PKU: Peking University)H-Index: 14
Last.Wendell A. Lim (UCSF: University of California, San Francisco)H-Index: 72
view all 3 authors...
#1Albert J. Keung (BU: Boston University)H-Index: 14
#2Caleb J. Bashor (BU: Boston University)H-Index: 6
Last.Ahmad S. Khalil (Wyss Institute for Biologically Inspired Engineering)H-Index: 18
view all 5 authors...
Cited By2
Newest
#1Andrew H. NgH-Index: 4
#2Taylor H. Nguyen (UCSF: University of California, San Francisco)
Last.David Baker (UW: University of Washington)H-Index: 129
view all 11 authors...
#1Vittorio Bartoli (UoB: University of Bristol)
#2M. di Bernardo (UoB: University of Bristol)H-Index: 41
Last.Thomas E. Gorochowski (UoB: University of Bristol)H-Index: 12
view all 3 authors...
#1Andrew H. Ng (University of California, Berkeley)H-Index: 4
#2Hana El-Samad (UCSF: University of California, San Francisco)H-Index: 24
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