Date: 18th April 2019
How living cells read DNA and transform its information into complex decisions is one of the questions crucial to the success of the synthetic cell biologist. By understanding the complex signalling components and pathways we can we potentially design artificial cells, tissues, organs and cell-based therapies. With this in mind bioengineers from the US have developed synthetic transcriptional circuits that produce nonlinear behaviour to mimic the complex functions performed by a cell.
Transcription factors regulate gene expression which can in turn direct a cell to make a complex decision whether it be, for example, a lineage choice during development or cellular differentiation. Due to the intricate nature of the cell, these transcription factors often function as multivalent complexes; cooperative self-assemblies that perform non-linear regulatory operations and enable binary-like responses to emerge from a multi-facetted input when all the parts (or transcription factors) come together and the switch is “flicked”. Now Caleb Bashor and a team in Science journal have applied the principle of cooperative self-assembly to synthetic networks and in the process created a digital-to-analogue converter whereby yeast cells were able to respond to varying concentrations of chemical inputs as part of a continuous graded response (analogue) or an all or nothing response (digital). Furthermore, by adjusting the strength and size of the assembly subunits in the cooperative assemblies, they were able to enable predictive tuning between these two responses and dynamically control the sharpness of the response, from dull to sharp. In essence, the larger the complex the sharper the response.
This ability to model and synthesise complex regulatory programmes will be a valuable tool for the bioengineer. Whilst simpler forms of cell-based signal processing have been achieved this marks the first example of synthetic circuits influencing decisions in a Boolean or switch-like manner. The Bashor lab’s research focuses on the application of synthetic circuits and pathways to engineer cell-based therapies and we will watch with interest how the findings reported here can be translated.
Bashor, C. J., N. Patel, S. Choubey, A. Beyzavi, J. Kondev, J. J. Collins and A. S. Khalil (2019). “Complex signal processing in synthetic gene circuits using cooperative regulatory assemblies.” Science: eaau8287.