Signal Amplification in Synthetic Bacterial Communication

Citation

Parkin, James Michael (2021) Signal Amplification in Synthetic Bacterial Communication. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/50p8-bd89. https://resolver.caltech.edu/CaltechTHESIS:03262021-160841703

Abstract

Synthetic biology will one day enable embedded control of a variety of chemical and biological contexts, from the human gastrointestinal tract to crop roots. Groups of engineered organisms, also known as synthetic consortia, can inhabit niches of interest while monitoring and intervening according to their genetic design. However, the spatial structure of the deployment environments can obstruct coordination between cosortia members. The mechanisms engineered bacteria use to communicate must contend with these adversarial conditions to maximize group performance.

Coordination between synthetic bacteria is typically achieved using small molecules that can traverse cell membranes through passive transport. Cell communicate by producing and sensing these small molecules. In cell-cell signaling relationships composed of a sender population and a receiver population, the concentration of signaling molecule sensed by the receiver cells depends on the spatial patterning of the two groups, the geometry of the diffusive environment, and the sender population’s signal secretion rate.

To make sender-receiver communication more robust to these environmental features, we introduce a third consortium strain that transiently amplifies local signaling molecule concentrations. These amplifier cells employ a synchronized pulse-generating circuit built using Lux-type quorum sensing components and an IFFL transcriptional architecture. When applied to sender-receiver consortia growing on semi-solid media, these amplifier cells respond to sender-secreted signaling molecules by contributing a small amount themselves. The support of amplifier cells enables communication over longer distances than can be achieved by sender cells alone and can partially recover coordination in small consortia where the sender population is too small to successfully signal its receiver population alone. We extend these results using simulation to investigate the benefit that amplifier cells confer to consortia of varying complexity.

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