Preventing Evolutionary Failure in Synthetic Biology

Synthetic biology seeks to apply engineering principles to create living systems with predictable and useful behaviors from collections of standardized genetic parts. However, living systems – unlike mechanical devices – inevitably evolve when their DNA sequences accumulate copying errors. Cell growth often favors "broken" mutants carrying malfunctioning devices. For engineering efforts from the scale of educational projects building simple genetic circuits to international research consortia rebuilding entire genomes, stopping or slowing evolution would greatly improve the reliability of biological engineering. We are using a directed evolution strategy (PResERV, Periodic Reselection of Evolutionarily Reliable Variants) and rational modifications of DNA repair and replication pathways to create mutant cells with lower-than-natural mutation rates. These cells will serve as more evolutionarily reliable "chassis" for synthetic biology.