Science Focus Area: Lawrence Livermore National Laboratory
- Principal Investigator: Yongqin Jiao1
- Laboratory Research Manager: Felice Lightstone1
- Co-Investigators:Dan Park,1 Mimi Yung,1 Dante Ricci,1 Jonathan Allen,1 Jennifer Listgarten,2 Harris Wang,3 W. Seth Childers4
- Participating Institutions: 1Lawrence Livermore National Laboratory, 2University of California–Berkeley, 3Columbia University, 4University of Pittsburgh
- Project Website: https://sc-programs.llnl.gov/biological-and-environmental-research-at-llnl/secure-biosystems-design
Summary
Genetically engineered microorganisms (GEMs) play an important role in building and maintaining a sustainable bioeconomy. Without sufficiently robust biocontainment strategies, however, technology adoption and public trust will remain low. To reduce the risk of unintended ecological consequences from environmentally deployed GEMs, Lawrence Livermore National Laboratory’s (LLNL) BioSecure Science Focus Area (SFA) focuses on developing built-in security mechanisms that ensure GEM function where and when needed. Through containment mechanisms that can withstand the forces of evolution, these tools prevent the unwanted spread of GEMs without compromising their ability to thrive and function. Leveraging LLNL’s high-performance computing and high-throughput gene-editing capabilities, efforts are concentrated on accelerating sequence entanglement as a generalizable biocontainment tool. In this strategy, two genes are encoded as overlapping sequences within the same DNA molecule, taking advantage of the fact that the same DNA sequence can be decoded in different reading frames. This DNA sequence overlap protects engineered functions against mutational inactivation and mitigates the potential transfer of engineered genes to naturally occurring microbes. Building on the foundation of sequence stability, additional containment strategies are incorporated to regulate the survival and functionality of microbes in response to environmental cues. These include protein translation based on the presence of unnatural amino acids and post-translational modifications of proteins based on chemical or light signaling. To enhance the system’s resilience to environmental fluctuations, additional controls for population coordination through quorum sensing and horizontal gene transfer are incorporated. Ultimately, these containment strategies will be broadly applicable across a wide range of microorganisms, leading to a safer and more sustainable bioeconomy.