Synthetic genetic circuits can perform complex biological functions, e.g., making decisions and keeping track of time, by harnessing living organisms’ intercellular machinery. Traditionally, they are implemented in mono-species bacterial systems, i.e., a single cell-type, and can simultaneously sense up to four inputs and four fluorescence outputs. Increasing the complexity of biological functions requires increasing the number of inputs, outputs, which causes metabolic burden in host organisms. On the other hand, microbial communities allow for increasing complexity by dividing labor among species, i.e., splitting large circuits into multi-cellular circuits connected by intercellular signals. Here, we first demonstrate a tool for breaking large networks into sub-circuits that can be implemented into bacterial communities. Second, we built five different sender-receiver pairs carrying multicellular SR latches, leveraging independent quorum-sensing systems and YFP sensors to report the dynamics of communication and circuits. Next, a massively parallel microfluidic microscopy set-up with spatial and temporal control was developed to characterize the dynamics of multicellular sequential logic circuits (SR latches) in synthetic microbial communities. Then, we used signal processing tools to independently investigate how the dynamics of novel intercellular signaling modules affect the functionality of temporal logic circuits (SR latches, i.e., genetic memory devices) in synthetic communities.

Characterizing the dynamics of bacterial multicellular circuits using controllable microfluidic devices

ACS Spring 2022

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