Science Focus Area: National Renewable Energy Laboratory
- Principal Investigator: Michael Guarnieri1
- Laboratory Research Manager: Adam Bratis1
- Co-Investigators: Jeffrey Linger1, Katie Arnolds1, Jianping Yu1, Wei Xiong1, Karsten Zengler2, Yo Suzuki3, Clifford Louime4
- Participating Institutions: 1National Renewable Energy Laboratory, 2University of California-San Diego, 3J. Craig Venter Institute, 4University of Puerto Rico, Rio Piedras

Secure Biosystems Design Platform. The IMAGINE SFA led by the National Renewable Energy Laboratory (NREL) has established an integrative and iterative biocontainment platform to build, characterize, and predictively design biocontainment in microbial systems. Trackable biocontainment modules are incorporated in industrial microbes using genome-scale engineering strategies. The resultant engineered microbes are experimentally analyzed to assess their growth, escape frequency, and bioproductivity using high-throughput screening analyses in laboratory and environmental settings, including bioreactor scaleup and plant-soil microbe mesocosm deployment. Genome-scale metabolic modeling is applied to develop a systems understanding of the underlying mechanisms that govern the efficacy of biocontainment and metabolic fitness. Model-informed knowledgebases enable iterative improvement of biocontainment designs with the goal of establishing predictive design capacity. [Courtesy NREL]
Summary
Microbial biocatalysts and bio-derived products have emerged as an integral component of a sustainable bioeconomy, with an array of applications in agriculture and bioenergy. However, the rapid development of genetically engineered microbes and associated synthetic biology approaches raises several biosecurity concerns related to microbial environmental escape, detection, and impact upon native ecosystems. To establish a secure bioeconomy, novel biocontainment strategies that do not compromise laboratory performance are needed. To this end, the Integrative Modeling and Genome-scale Engineering for Biosystems Security (IMAGINE) Science Focus Area (SFA) team was established to accomplish the overarching goal of achieving predictive control of engineered systems to enable secure biosystems design.
The IMAGINE team integrates core capabilities in synthetic and systems biology, computational modeling, and plant-soil microbiology to develop a high-throughput platform for the design, generation, and analysis of biocontainment strategies in DOE-relevant and next-generation industrial microbes. IMAGINE leverages the National Renewable Energy Laboratory’s (NREL) metabolic engineering and multiscale omics capabilities in industrial microbial hosts and its unique pilot-scale deployment capacity to expand the U.S. Department of Energy’s knowledgebase into deployment-relevant systems. These capabilities are complemented by expertise in synthetic genomics (J. Craig Venter Institute), environmental microbiology (University of Puerto Rico), and genome-scale and community metabolic modeling (University of California-San Diego) to enable predictive design strategies for next-generation microbial production platforms.
The IMAGINE SFA is actively developing an extensive library of biocontainment modules and strains, a testing and characterization platform, and genome-scale computational tools to rapidly integrate genome-scale systems data. These outputs are laying the foundation for predictive design of biocontainment strategies with enhanced stability and resilience in diverse microbial hosts, while maintaining maximal fitness and bioproductivity of the engineered microbial strains. Combined, these efforts will reduce the risk associated with deployment of engineered biosystems and ultimately advance a secure bioeconomy.