Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies

• Main Authors: Bashor, Caleb J. (Author), Patel, Nikit (Author), Choubey, Sandeep (Author), Beyzavi, Ali (Author), Kondev, Jané (Author), Collins, James J. (Author), Khalil, Ahmad S. (Author)
• Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Synthetic Biology Center (Contributor)
• Format: Article
• Language: English
• Published: American Association for the Advancement of Science (AAAS), 2020-07-22T18:25:40Z.
• Subjects: Article
• Online Access: Get fulltext

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.
DARPA (Grant W911NF-11-2-0056)