Sculpting Ecosystems

Wild organisms are exquisitely adapted to surviving and reproducing in their ancestral habitat. That means the vast majority of mutations will be harmful and the same is true of human-designed changes. Natural selection consequently eliminates our alterations, preventing us from using biology to stably change ecosystems.

On the rare occasions that we can provide a fitness benefit - typically by engineering the environment - the responsible genes are hard to link to other traits and readily transfer into wild-type competitors. Thus, if we want to engineer biology outside of the controlled environments of the laboratory, clinic, and factory, we must learn to establish, link, and maintain fitness advantages.

The best solution to this problem involves gene drives, which benefit associated alterations by distorting inheritance in their favor. We outlined how RNA-guided gene drives based on Cas9 might be used to drive many types of genomic alterations through wild populations over generations.

Current projects in the gene drive area involve building and testing safeguard technologies for the responsible development of gene drives, including immunizing reversal, cyclic and daisy drive systems.

We also develop ways of privileging engineered microbes over wild counterparts by conferring evolutionarily stable resistance to bacteriophages, which we are using to precisely replace target strains within complex microbial ecosystems.