Abstract

Bacteriophage-based cell-cell communication allows users to create genetically dynamic bacterial ecologies by transmitting DNA molecules between E. coli cells. In previous work, I demonstrated how such a system could be used to transmit DNA messages having different functionalities to develop ecologies over hours-long time courses in liquid or over solid media. If well-designed, such ecologies have the ability to compute, amplify, or report state as a population.

One immediate problem encountered in designing stable bacterial ecologies is that relatively small differences in individual growth rates can impact the resulting population mix in little time. As such, we have focused on developing optimization-based tools for relating the initial and final states of heterogeneous baterial ecologies. We have created a scalable model of the phage-based communication platform to aid development of more complex engineered bacterial ecologies. By inputting few experimental parameters as well as an arbitrary desired output behavior, users can easily obtain the necessary inputs to their engineered system. As phage-based communication via DNA transmission inherently creates genetically distinct species as phage infection proceeds, this tool also enables the user to design and optimize for time-varying behaviors. Overall, it is hoped that such tools will enable greater complexity of heterogeneous bacterial mixtures, help us better understand ec ologies, and allow us to narrow the gap between natural and synthetic systems.