Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies
Author(s)Bashor, Caleb J.; Patel, Nikit; Choubey, Sandeep; Beyzavi, Ali; Kondev, Jané; Collins, James J.; Khalil, Ahmad S.; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Institute for Medical Engineering and Science; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Synthetic Biology Center
American Association for the Advancement of Science (AAAS)
Bashor, Caleb J. et al. "Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies." Science 346, 6440 (May 2019): 593-597 © 2019 American Association for the Advancement of Science
Author's final manuscript