An Investigation into Ratiometric Control for Synthetic Ecosystems

In nature, cooperation between microbes allow microbial ecosystems to resist through fluctuating environmental conditions and produce complex substances necessary for their survival. Synthetic biologists want to harness the potential of such ecosystems for their own purposes and thus are investigating ways to build stable synthetic ecosystems. However their synthetic consortia often grow out of balance when some strains present growth advantages and outcompete the remaining strains in the consortia, leading to a loss of function of their systems. Here we design gene circuits in E. coli to achieve growth regulation that do not rely on the use of gene knockouts in order to conserve optimal growth properties and activate the controller only when the consortium becomes unstable. We focus on the development of an RNA-based controller capable of sensing cell density and regulating growth in the context of host-aware synthetic biology. This investigation is a first step in understanding how RNA could be used as a highly engineerable platform to control growth rates in stable synthetic ecosystems for applications in metabolic engineering.