Engineered temperature compensation in a synthetic genetic clock
Abstract
Synthetic gene circuits are often fragile, as perturbations to cellular conditions frequently alter their behavior. This lack of robustness limits the utility of engineered gene circuits and hinders advances in synthetic biology. Here, we demonstrate that environmental sensitivity can be reduced by simultaneously engineering circuits at the protein and network levels. Specifically, we designed and constructed a synthetic genetic clock that exhibits temperature compensation—the clock's period does not depend on temperature. This feature is nontrivial since biochemical reactions speed up with increasing temperature. To accomplish this goal, we engineered thermal-inducibility into the clock's regulatory structure. Computational modeling predicted and experiments confirmed that this thermal-inducibility results in a clock with a stable period across a large range of temperatures.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- January 2014
- DOI:
- 10.1073/pnas.1316298111
- Bibcode:
- 2014PNAS..111..972H