Secure Biosystems Design Scientific Focus Area

Designing secure biosystems to protect environmental microorganisms.

Genetically engineered microorganisms (GEMs) play an important role in building and maintaining a sustainable bioeconomy. To reduce the risk of unintended ecological consequences from environmentally deployed GEMs, the Secure Biosystems Design Scientific Focus Area (SFA) at LLNL is developing built-in security mechanisms that ensure GEMs function where and when needed.

Our security mechanisms will help safeguard the deployment of engineered microbes in the rhizosphere (the narrow region of soil directly influenced by root secretions and associated soil microorganisms known as the root microbiome). Additionally, layered containment strategies at the sequence, cellular, and population levels are expected to increase the overall system robustness to environmental fluctuations.

By stabilizing GEMs and preventing the transfer of potentially invasive traits to native microbiomes, our ultimate objective is to control the niche-specific function of GEMs for safer and more effective environmental applications.

Explore this page to learn more about our research and capabilities.


Multilayered containment strategies can safeguard the deployment of engineered microbes in the rhizosphere. Image courtesy of Dan Park (LLNL).

With vast potential for use in large-scale applications, GEMs are critical in building and maintaining a sustainable bioeconomy. The need for biocontainment strategies is particularly relevant for the sustainable development of bioenergy crops and carbon sequestration. The microbiota colonizing the rhizosphere of plant roots, especially plant-benefiting microorganisms (PBMs), contribute to plant growth and modulate soil carbon input, release, and storage. Genetic engineering approaches have been used to enhance the beneficial traits of PBMs, such as nutrient acquisition and drought resistance.

Our work focuses on establishing robust biocontainment strategies in soil microbes at the DNA sequence, cellular, and population levels without sacrificing microbial fitness. Leveraging LLNL’s high-performance computing (HPC) and high-throughput gene-editing capabilities, we will advance a synthetic gene entanglement strategy for containment. In this method, two genes are encoded as overlapping sequences within the same DNA molecule to protect engineered functions against mutational inactivation and mitigate the potential transfer of engineered genes to naturally occurring microbes.

Building on this layer of genetic stability, our team will incorporate additional strategies that control cellular physiology and direct population coordination to increase the overall system robustness to environmental fluctuations. With the help of the “Microbes Persist” Soil Microbiome SFA at LLNL and their rich experience in soil microbial ecology, we will evaluate the ecological benefits of these containment mechanisms in soil and rhizosphere environments. Ultimately, our biosystem designs—created to improve gene fitness, function, and evolutionary stability—will provide a knowledge base to enable safer use of GEMS in distinct applications like plant probiotics, carbon sequestration, metal recovery, nuclear-activity detection, and biomaterial production.


Our core capabilities in genome editing and analysis enable effective GEM containment.


Comparison of phage-derived recombinases for genetic manipulation of Pseudomonas species | BioRvix, 2023

M. J. Kalb, A.W. Grenfell, A. Jain, J. Fenske-Newbart, J.A. Gralnick

Electrogenetic signaling and information propagation for controlling microbial consortia via programmed lysis | Biotechnol. Bioeng., 2023

E. VanArsdale, A. Navid, M.J. Chu, T.M. Halvorsen, G.F. Payne, Y. Jiao, W.E. Bentley, M.C. Yung

Fast and efficient template-mediated synthesis of genetic variants | Nature Methods, 2023

L. Liu, Y. Huang, H.H. Wang

Prolonging genetic circuit stability through adaptive evolution of overlapping genes | Nucleic Acids Research, 2023

J.L. Chlebek, S.P. Leonard, C.S. Kang-Yun, M.C. Yung, D.P. Ricci, Y. Jiao, D.M. Park

Comparison of kill switch toxins in plant-beneficial Pseudomonas fluorescens reveals drivers of lethality, stability, and escape | ACS Synth. Biol., 2022

T.M. Halvorsen, D.P. Ricci, D.M. Park., Y. Jiao, and M.C. Yung

Electrogenetic signal transmission and propagation in coculture to guide production of a small molecule, tyrosine | ACS Synth. Biol., 2022

E. VanArsdale, J. Pitzer, S. Wang, K. Stephens, C-Y. Chen, G.F. Payne, and W.E. Bentley

Learning protein fitness models from evolutionary and assay-labeled data | Nat. Biotechnol., 2022

C. Hsu, H. Nisonoff, C. Fannjiang, and J. Listgarten

Mediated electrochemistry for redox-based biological targeting: entangling sensing and actuation for maximizing information transfer (Review) | Curr. Opin. Biotechnol., 2021

D. Motabar, J. Li, G.F. Payne, and W.E. Bentley

Electronic signals are electrogenetically relayed to control cell growth and co-culture composition | Met. Eng. Comm., 2021

K. Stephens, F.R. Zakaria, E. VanArsdale, G.F. Payne, and W.E. Bentley

Mediated Electrochemical Probing: A Systems-Level Tool for Redox Biology | ACS Chem. Biol., 2021

Z. Zhao, E.E. Ozcan, E. VanArsdale, J. Li, E. Kim, A.D. Sandler, D.L. Kelly, W.E. Bentley, and G.F. Payne

Interactive Materials for Bidirectional Redox‐Based Communication | Adv. Mater., 2021

J. Li, S.P. Wang, G. Zong, E. Kim, C.-Y. Tsao, E. VanArsdale, L.‐X. Wang, W.E. Bentley, and G.F. Payne

Synthetic sequence entanglement augments stability and containment of genetic information in cells | Science, 2019

T. Blazejewski, H-I. Ho, and H.H. Wang


Our multi-institutional team includes experts in bioscience and biotechnology.


Yongqin Jiao

Yongqin Jiao

Lead Principal Investigator

Jonathan Bethke

Jonathan Bethke

Chenling Xu

Chenling Xu

Bentley Lim

Bentley Lim

Columbia University

University of California, Berkeley

University of Pittsburgh

Previous members

  • Jennifer Pett-Ridge (LLNL)
  • Adam Zemla (LLNL)
  • Ali Navid (LLNL)
  • Matt Coleman (LLNL)
  • Jose Manuel Marti Martinez (LLNL)
  • Tiffany Halvorsen (LLNL)
  • Fangchao Song (LLNL)
  • Tomasz Blazejewski (Columbia University)
  • Guillaume Urtecho (Columbia University)
  • Carlotta Ronda (Columbia University)
  • Charlotte Rochereau (Columbia University)
  • Jinyang Li (University of Maryland)
  • Eric VanArsdale (University of Maryland)
  • William Bentley (University of Maryland)
  • Gregory Payne (University of Maryland)
  • Rahma Zakaria (University of Maryland)
  • Jeffrey Gralnick (University of Minnesota)
  • Madison Kalb (University of Minnesota)
  • Chloe Hsu (UC Berkeley)
  • Akosua Busia (UC Berkeley)