Tae Seok Moon, Ph.D.

Assistant Professor
Energy, Environmental & Chemical Engineering

Plant and Microbial Biosciences Program
Molecular Microbiology and Microbial Pathogenesis Program
Computational and Systems Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-935-5026

  • 314-935-7211

  • 1180

  • One Brookings Dr. Brauer Hall Rm. 3046

  • tsmoon@WUSTL.EDU

  • https://eece.wustl.edu/faculty/Pages/faculty.aspx?bio=58

  • Synthetic Biology; Systems Biology; Metabolic Engineering; Protein Engineering; Genetic Circuits

  • Building the Future with Synthetic Biology

Research Abstract:

Mission
Since the advent of genetic engineering in the 1970s, engineered cells have been used to produce recombinant proteins and chemicals. Recently, interest in cellular engineering for chemical production has been intensified with the depletion of non-renewable resources. The past decade has witnessed the potential of synthetic biology, an emerging field where engineering principles are applied to biology in order to create programmable cells for real-world applications. However, engineering biology is quite different from other engineering disciplines, and many challenges remain to make living systems conform to engineering principles. First, unlike electronic or mechanical parts, genetic parts tend to change. Cells work for themselves and disfavor exploitation against their survival. Thus, recombinant DNA is often mutated if no selective pressure exists to maintain its function. Second, orthogonality is difficult to implement in biology. Orthogonality means that system components can be varied independently without affecting the performance of the other components. It is the prerequisite for dividing a system into small parts and developing them independently. In non-biological systems, there are many simple strategies to ensure orthogonality. For example, a series of chemical reactions can be confined to separate reactors to prevent side reactions. In contrast, various reactions and interactions occur in a bacterial cell. Thus, there is a high chance of cross-talks even when a single recombinant gene is introduced.

The key to solving such problems is to implement synthetic control over biological processes such as evolution, gene expression, and chemical reactions. My research interests are focused on developing and controlling microbes that are able to process multiple input signals and to produce desirable outputs. Specifically, I aim to create synthetic gene circuits in order to control metabolic pathways and improve productivity of biomass-based chemicals and drugs. Combining 1) my expertise in the design and construction of orthogonal metabolic pathways and genetic circuits and 2) my experience in the biotechnology industry, I will help transform synthetic biology from a “toy” building practice into an application-oriented engineering activity.

Long Term Vision
Many applications require cells to integrate multiple environmental signals and to implement synthetic control over biological processes. Genetic circuits enable cells to perform computational operations, interfacing biosensors and actuators. Despite advances in the rational construction of genetic circuits, practical applications of genetic circuits have yet to be realized. Cells equipped with an internal cell state controller may respond quickly to fluctuation of pH and O2/acetate/redox levels in a heterogeneous large bioreactor, leading to less stress and more production. Autonomously navigating cells can be created to detect and destroy toxic chemicals, pathogens, and tumor cells. Engineering cells in a lab scale is entirely different from creating microbial cell factories and environmental janitors that face various changing signals. For such real-world applications, systems must be robust and resistant to mutations for an extended use. In addition, orthogonal genetic parts are needed to build complex circuits. My long term goal is constructing programmable cells that are able to process multiple input signals and to produce desirable outputs to solve energy, environment, and health problems. It is time to create useful biological systems rather than toy systems.

Selected Publications:

1. A Hoynes-O’Connor and TS Moon. Development of design rules for reliable antisense RNA behavior in E. coli. ACS Synth. Biol. Accepted. DOI: 10.1021/acssynbio.6b00036 (2016)

2. YJ Lee, A Hoynes-O`Connor, MC Leong and TS Moon. Programmable control of bacterial gene expression with the combined CRISPR and antisense RNA system. Nucleic Acids Res. 44, 2462–2473 (2016)

3. A Yoneda, WR Henson, NK Goldner, KJ Park, KJ Forsberg, SJ Kim, MW Pesesky, M Foston, G Dantas and TS Moon. Comparative transcriptomics elucidates adaptive phenol tolerance and utilization in lipid-accumulating Rhodococcus opacus PD630. Nucleic Acids Res. 44, 2240–2254 (2016)

4. CM Immethun, KM Ng, DM DeLorenzo, B Waldron-Feinstein, YC Lee and TS Moon+. Oxygen-Responsive Genetic Circuits Constructed in Synechocystis sp. PCC 6803. Biotechnol. Bioeng. 113, 433-442 (2016)

5. T Shopera, WR Henson, A Ng, YJ Lee, K Ng and TS Moon. Robust, tunable genetic memory from protein sequestration combined with positive feedback. Nucleic Acids Res. 43, 9086-9094 (2015)

6. A Hoynes-O’Connor, K Hinman, L Kirchner and TS Moon. De novo design of heat-repressible RNA thermosensors in E. coli. Nucleic Acids Res. 43, 6166–6179 (2015)

7. A Hoynes-O’Connor and TS Moon. Programmable genetic circuits for pathway engineering. Curr. Opin. Biotechnol. 36, 115-121. Invited Review (2015)

8. TS Moon, C Lou, A Tamsir, BC Stanton and CA Voigt. Genetic Programs Constructed from Layered Logic Gates in Single Cells. Nature 491, 249-253 (2012)

9. TS Moon, EJ Clarke, ES Groban, A Tamsir, RM Clark, M Eames, T Kortemme and CA Voigt. Construction of a Genetic Multiplexer to Toggle between Chemosensory Pathways in Escherichia coli. J. Mol. Biol. 406, 215-227 (2011)

10. JE Dueber, GC Wu, GR Malmirchegini, TS Moon, CJ Petzold, AV Ullal, KJ Prather and JD Keasling. Synthetic Protein Scaffolds Provide Modular Control over Metabolic Flux. Nat. Biotechnol. 27, 753-759 (2009)

Last Updated: 8/25/2016 12:03:40 PM

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