Development of Sophisticated Biosynthetic Analog-to-digital Signal Processors Hold Key to Emulation of Natural Eukaryotic Cell Function

Jason Wang 22′

Bioengineers have developed a considerably more sophisticated method of biosynthetic analog-to-digital signal processing. A recent report co-led by Caleb Bashor of Rice University and Ahmad Khalil of Boston University marks a departure from prior research in the field and a significant step forward in the development of such technology. Published online in Science, this research improves the precision and capabilities of synthetic signal processing with notable implications for immune and stem cell functions.

The key scientific departure from previous work in the field of biosynthetic signal processing is Bashor and Khalil’s use of cooperative assembly design principles in their synthetic signal processors. Prior work in the field of synthetic signal processing primarily involved transcription factors that bound to promoters in a singular fashion, independent of other components within the molecular system. In eukaryotes, on the other hand, an interconnected network of transcription factors and co-factors enables quick, precise, and dynamic signal processing. This synthetic binary activation mechanism severely limited the variability and flexibility of these basic synthetic signal processors, which were unable to emulate the behavior and functionality of natural signal processors.

Cooperative assembly describes the coordinated behavior of mutually-reinforcing complex interactions between multiple transcription factors, enabling greater sophistication in signal processing functionality. Bashor and Khalil developed a synthetic cooperative transcription factor assembly mechanism involving synthetic zinc-finger proteins, transcriptional activator domains, DNA binding motifs, and core promoters. The research team proceeded to test the cooperative functionality with both in vitro and in vivo yeast cell experimentation, quantifying and verifying the dynamic signal cell functionality with a variety of statistical analyses.

This research has remarkable implications for the development of biosynthetic technology, particularly with regard to medical applications. The nonlinear nature of transcription factor complexes in cooperative assembly could enable the use of such technology in synthetic gene circuits, claims study co-author James Collins of MIT, Harvard, and the Broad institute. Bashor and Khalil’s research validates synthetic signal processing as a suitable and effective emulator of natural eukaryotic cell function. Possible applications may include the use of the analog-to-digital signal processing in developing synthetic regulatory programs and cell-based therapeutics to improve immune, and stem cell functionality.

 

References

1. Bashor, C. J., Patel, N., Choubey, S., Beyzavi, A., Kondev, J., Collins, J. J., & Khalil, A. S. (2019). Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies. Science, eaau8287. https://doi.org/10.1126/science.aau8287
2. Keiono. (2007). English: Human Interactome network visualized by Cytoscape 2.5. Retrieved from https://commons.wikimedia.org/wiki/File:Human_interactome.jpg
3. Rice University. (2019, April 18). Bioengineers program cells as digital signal processors. Retrieved April 27, 2019, from ScienceDaily website: https://www.sciencedaily.com/releases/2019/04/190418141554.htm