Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies.

Authors:
Caleb J Bashor
Caleb J Bashor
Boston University
United States
Nikit Patel
Nikit Patel
Boston University
Ali Beyzavi
Ali Beyzavi
Nanyang Technological University
Singapore
James J Collins
James J Collins
Boston University
United States
Ahmad S Khalil
Ahmad S Khalil
Howard Hughes Medical Institute
United States

Science 2019 05 18;364(6440):593-597. Epub 2019 Apr 18.

Department of Biomedical Engineering and Biological Design Center, Boston University, Boston, MA 02215, USA.

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.

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Source
http://www.sciencemag.org/lookup/doi/10.1126/science.aau8287
Publisher Site
http://dx.doi.org/10.1126/science.aau8287DOI Listing
May 2019
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