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미래를 창조하는 포스텍 화학공학과

Synthetic Biology Toward Construction of Programmable Molecular and Ce…

일자
2017.2.14(화)
시간
16:30
연사
이정욱 박사
장소
환경공학동 111호
[Abstract]
Synthetic biology uses living cells as molecular foundries for the biosynthesis of drugs, therapeutic proteins, and other commodities. The key challenges in current synthetic biology are in the reliability, robustness, flexibility and security of new biological designs for practical applications. In this talk, cell-based efforts on genetic circuit development will be described to address these issues in the first place. Empirical design, mathematical modeling, and iterative construction and testing were used to build single-copy genetic circuits. Upon integration into the host genome, the circuit performance was improved with reduced metabolic load. Deterministic and stochastic models led us to focus on basal transcription to optimize circuit performance and helped to explain the resulting circuit robustness across a large range of component expression levels. The logic in the molecular circuit was then expanded to develop biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. These synthetic gene circuits efficiently killed Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism. In the second part, a portable platform that provides the means for on-site, on-demand manufacturing of therapeutics and biomolecules will be described. This flexible system is based on reaction pellets composed of freeze-dried, cell-free transcription and translation machinery, which can be easily hydrated and utilized for biosynthesis through the addition of DNA encoding the desired output. This approach was demonstrated with the manufacture and functional validation of antimicrobial peptides and vaccines, and present combinatorial methods for the production of antibody-conjugates and small molecules. Finally, the freeze-dried cell-free system was employed as a biological platform to perform molecular diagnostics. In combination with toehold switches, a femtomolar level of Zika virus from plasma of a viremic macaque was identified in a simple, and field-ready workflow. Overall, the given cell-based and cell-free biological platform that resolves important practical limitations facing many different applications demonstrate how synthetic biology can be used to develop future molecular and cellular devices for therapeutics and molecular diagnostic tools.