BII-Design: Using Synthetic Biology to Discover Cross-Kingdom Metabolic Rules of Life

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Synthetic biology (SynBio) is a revolutionary combination of engineering and life sciences. It empowers investigators to design and build from the ground up useful new biological systems such as metabolic pathways. SynBio can also uncover the deep operating principles that underlie biological systems – the ‘Rules of Life’. This is done by applying the build-to-learn philosophy, i.e. (i) design and construct biosystems based on current knowledge of the Rules; (ii) if the systems don’t perform as predicted, diagnose why and thus deepen knowledge of the Rules. Despite its intellectual power and practical potential in metabolic engineering, SynBio has been slow to reach plant biology and SynBio training has historically been concentrated in engineering schools where women and other groups are notably underrepresented. There is consequently an urgent need to bring SynBio into mainstream plant metabolism research and diversified training, and to use SynBio’s build-to-learn philosophy to define Rules for redesigning plant metabolism. This project will accordingly harness the complementary SynBio strengths of three leading plant science universities to design a tri-campus PhD training and research program to define Rules to guide engineering of novel metabolic pathways. The project will be designed in virtual workshops, one hosted by each campus. Design goals will be to (i) integrate basic engineering skills and internships in SynBio companies into PhD training, leading to an interuniversity graduate research certificate, and (ii) develop strategies to recruit women to redress the gender imbalance in engineering. The workshops will also help plan a major 2021 Plant SynBio Conference, which Co-PI Lenaghan will chair. Synthetic biology (SynBio) has the power to change biology from a descriptive to a prescriptive discipline and to transform plant improvement, particularly of metabolic traits. However, perhaps because its roots are in chemical engineering, the SynBio revolution has barely reached plant science yet. To address the critical shortage of SynBio PhD training for plant scientists, and the underrepresentation of women in the field, plant scientists and metabolic engineers at three major plant science universities (University of Florida, University of Tennessee, and Purdue University) have come together in this project to pool their complementary expertise to design a coordinated three-campus PhD training and research program in SynBio. The project will hold three virtual workshops (one hosted by each university) to plan a graduate certificate in SynBio and a concerted research plan to define Rules of Life that (i) predict how well enzymes and metabolic pathways developed in microbial SynBio platforms will transfer to plants, and (ii) enable the amount, stoichiometry, and timing of enzyme activity to be adjusted to assure efficient operation of new multienzyme pathways in plants. In the certificate program, online flipped-classroom courses will be given in their areas of expertise by each university and SynBio companies will be recruited to host internships for students. Courses will cover basic coding, engineering principles, metabolic engineering, synthetic regulatory circuits, and directed evolution. The workshops will also plan strategies to recruit women. Lastly, the workshops will help plan the American Society of Plant Biologists’ 2021 SynBio Conference, which Co-PI Lenaghan will chair.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.