Collaborative Research: Closed-loop control of microbial communities by integrating optogenetics and metabolite biosensing

Biotechnology is essential to the nation’s interest in scientific progress and maintaining world leadership in key strategic areas such as biomanufacturing, biomedical research, renewable energy, sustainability, and food production. While microbial bioprocesses are dominated by monocultures, utilization of synthetic microbial communities holds enormous potential for many applications in biotechnology, including production of high value chemicals. However, the lack of effective controls over key attributes of these communities impedes the development of this research field. This project will use metabolite biosensors and novel optogenetic growth control systems to modulate microbial community composition and to increase production of the desired chemical products. This project will generate new knowledge and methods to advance basic research in synthetic microbial communities and generate strategies for improved production of important chemicals. Moreover, this project will offer outstanding opportunities to engage high school, undergraduate, and graduate students in STEM education. The overall goal of this project is to integrate optogenetic controls and metabolite biosensing to achieve unprecedented automated dynamic regulation of microbial communities. Optogenetics offers the unique ability to control biological functions with light, which can be added or removed instantly and reversibly following any prescribed schedule. For this project, optogenetics will be used to modulate the growth of targeted microbes and ultimately to adjust contributions to bioproduction. Metabolite biosensing will provide instant feedback on the metabolic state of microbial communities to inform optogenetic actuators, establishing closed-loop feedback controls. This first-of-its-kind control system will be used to engineer interactions between members of microbial communities and their contributions towards collaborative biosynthetic pathways. It will also help identify the optimal community compositions throughout co-culture cultivation despite sup-optimal inoculums or system perturbations. Moreover, this project will explore the application of closed-loop controls in communities with different features, such as communities comprising members of the same or different species, containing linear or non-linear biosynthesis pathways, and capable of sensing biosynthetic pathway intermediates or final products. This project will open new opportunities to gain fundamental understanding of complex behaviors of synthetic microbial communities. This project is jointly supported by the Cellular and Biochemical Engineering, Biosensing and Biophotonics Programs in ENG/CBET, and the Systems and Synthetic Biology Program in BIO/MCB. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.