Dynamic Robust Control of Microbial Communities Using Cybergenetics

A key enabler for the engineering of complex biological systems is the co-culturing different cell strains together in a microbial community. Co-cultures can exhibit more diverse capabilities, increased robustness, and greater efficiency than a single strain engineered for a given application. However, reliable long-term control of such intricate systems is a complex task, and achieving communities that coexist stably despite potentially fluctuating cellular environments has been difficult to achieve. This challenge can be addressed by distributing signal processing between cells and computers through cybergenetics. Specifically, cellular outputs can be measured by sensors connected to a computer, which processes these signals and adjusts the cell culture conditions to achieve a desired goal; the cells then respond to this, closing the control loop. Striking a balance between computer-based and biological control implementations allows combining the strengths of the two approaches while circumventing their limitations. Here, we describe a methodology for cybergenetic control of microbial communities, considering the associated technical requirements, possible modes of interfacing between cell consortia and computers, and the resultant scope of biological and hardware design choices. This example illustrates how combining computational modeling with direct biological implementation of gene circuits leads to more robust and controllable systems with novel functionalities and applications.