開幕典禮及大會特別演講(一)

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P-3
Synthetic Biology for Biomedicine
Timothy Lu, MD, PhD
Assistant Professor
Massachusetts Institute of Technology

Synthetic biology is an emerging discipline for engineering biological systems with novel functionalities. This field promises to revolutionize our ability to diagnose and treat human diseases, to make and manipulate chemicals, and to enhance our understanding of natural biological systems. Synthetic biology is driven by significant advancements in our ability to sequence and synthesize DNA, two technologies that have been improving at rates which are comparable to or exceed the rate of semiconductor technology advancements.
Similar to other engineering disciplines, a foundational set of technologies are needed to enhance the reliability and speed at which biological systems can be designed. These include approaches for building libraries of well-characterized and orthogonal devices, assembling these devices into high-order systems, characterizing synthetic circuits in high throughput, and integrating experimental knowledge into predictive computational design tools. We recently described several novel platforms to enhance the engineering of synthetic circuits in living cells and have applied these technologies to design cells which can compute information. We have developed synthetic transcriptional regulation platforms that enable scalable tuning of transcriptional activity, specificity, and cooperativity within synthetic circuits and at endogenous genes in eukaryotic cells1,2. We also created a novel digital computational paradigm that enables integrated cellular decision-making, logic, and memory in living cells using libraries of orthogonal recombinase proteins3. We described an innovative strategy for implementing analog computation in living cells that enables wide-dynamic-range biosensing and the calculation of complex mathematical functions with a parsimonious set of devices4. We envision that these platforms for biological computing will enable more complex and powerful systems to be achieved inside of living cells.

Synthetic biologists have focused on several major application areas for biotechnology, diagnostic, and biomedical applications. Cells can be engineered into customized factories for chemicals, including biofuels, natural products, and specialty chemical products. Probiotic bacteria endowed with synthetic circuits could be used to detect and treat conditions of the gut. Recently, we have designed bacteriophages, which are viruses that infect bacteria, to act as rapid, sensitive, and specific detectors of microbial pathogens5. Furthermore, we have established several strategies for engineering bacteriophages to enhance the destruction of bacterial biofilms and resensitize antibiotic-resistant bacteria to antimicrobial therapy6,7. In summary, the impact of synthetic biology on biomedicine is just starting to be made and is sure to increase in the coming years. With its strengths in medicine, technology, and chemistry, Taiwan could be well-positioned to advance the foundations and applications of synthetic biology and to realize the potential economic and health benefits of this new technology.

1. Khalil, A., Lu, T.K., Bashor, C., Ramirez, C., Pyenson, N., Joung, J.K. & Collins, J.J. A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions. Cell 150, 647-658 (2012)
2. Farzadfard, F., Perli, S.D. & Lu, T.K. Tunable and Multi-Functional Eukaryotic Transcription Factors Based on CRISPR/Cas. ACS Synthetic Biology (2013)
3. Siuti, P., Yazbek, J. & Lu, T.K. Synthetic circuits integrating logic and memory in living cells. Nat Biotechnol (2013)
4. Daniel, R., Rubens, J.R., Sarpeshkar, R. & Lu, T.K. Synthetic analog computation in living cells. Nature 497, 619-623 (2013)
5. Lu, T.K., Bowers, J. & Koeris, M.S. Advancing bacteriophage-based microbial diagnostics with synthetic biology. Trends Biotechnol (2013)
6. Lu, T.K. & Collins, J.J. Engineered bacteriophage targeting gene networks as adjuvants for antibiotic therapy. Proceedings of the National Academy of Sciences of the United States of America 106, 4629-4634 (2009).2649960
7. Lu, T.K. & Collins, J.J. Dispersing biofilms with engineered enzymatic bacteriophage. Proceedings of the National Academy of Sciences of the United States of America 104, 11197-11202 (2007).1899193