[Lab Intro - KOR]

Programmable Designer Microorganisms by Systems and Synthetic Biology Approaches

- Elucidation of complex regulatory networks and reconstruction of meta-structure of microorganisms

- Building synthetic cell factories for the production of chemicals, fuels, pharmaceuticals, and therapeutics

- Building synthetic cells for environmental bio-remediation

- Building synthetic cells for biomedical applications

The ultimate research goals in SNU are 1) understanding the biological systems better by elucidating complex regulatory networks with high-throughput methods, 2) expanding design methods by development of biophysical models and molecular toolboxes for efficient genome/genetic engineering, and 3) designing optimal artificial cells based on this information so that cells can dynamically respond to environmental and/or intracellular metabolite changes by various sensors in a programmable manner for biochemical and biomedical applications. In order to achieve these goals, iterative rounds of systems/synthetic biology and evolutionary approaches would be needed. First, using systems biology approaches, complex biological regulatory networks need to be elucidated in order for us to efficiently identify engineering targets. Second, several key molecular tools for synthetic biology should also be developed for efficient engineering and/or design of biological systems. With these tools, biological systems should be engineered to 1) efficiently utilize renewable biomasses and 2) specifically sense various environmental changes to produce target products. Then, the engineered systems can be further evolved to meet the required 1) ranges of sensing and actuating capacities and 2) productivity and yield of target products. We can also profile what’s going on inside the cell with genome-scale analysis and re- utilize the information for further enhancement.

Meta-structure Reconstruction

Knowing what we are dealing with is the most important strategy to successfully engineer our targets. Although it had been several decades to study E. coli, there are still plenty of unknown regulatory mechanisms, networks, and interaction between them beyond the genomic sequence. Owing to the development of innovative high-throughput technologies, we can now have potentials to fully reconstruct meta-structure of bacterial regulatory networks beyond E. coli. We use the cutting-edge high-throughput genome-scale experimental methods such as ChIP-exo, RNA-seq, TSS-seq, and Ribo-seq to build a comprehensive regulatory network of bacterial genome. Comprehensive understanding of the meta-structure of bacteria will continue to enable applications in metabolic engineering, microbial engineering for energy, materials, and human health.

Synthetic Molecular Tools

Building a synthetic metabolic pathway requires molecular tools to design DNA sequence to achieve a specific expression level (static control) and a dynamic response of expression (dynamic control). We develop various molecular tools that can control multiple layers of regulation such as transcription, translation, and post-translation processes. Furthermore, we examine various approaches that can generate phenotypic diversity to evolve the engineered system to meet the expected performance.

Programming Cells

With various molecular tools, we program cells to solve issues in energy, environment, biomedical applications. For example, we design and construct de novo metabolic pathways to produce chemicals and fuels from renewable biomasses. Iteration of evolutionary approaches and genome-scale comprehensive analysis of the system would generate an economically feasible bioprocess. We also integrate multiple environmental signals and implement synthetic control over biological processes for various types of environmental and biomedical applications.