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BIOBOARD - FEATURE
Synthetic Biology in Singapore
Dong-Yup Lee and Kai Yu

*Corresponding author: Tel: +65 6516 6907; fax: +65 6779 1936.
Email address: cheld@nus.edu.sg

Introduction

Have you ever imaged that artificial living cells or organisms can be created just like the way you build toy castle using your Lego bricks? Although this sounds very much like a crazy idea from some science fiction movie that will not happen in the near future, this ambitious goal is what synthetic biology desires to achieve and enormous efforts are being put into this field to reshape the world we live in. So what exactly is synthetic biology? This is quite a tricky and arguable question, because the field of synthetic biology is still evolving rapidly so that no widely accepted definition exists. Some scientists insist that synthetic biology is focused solely on the development and standardization of "BioBricks"[1], called genetic circuits, based on modularity and specificity principles, thereby identifying and characterizing synthetic parts in cells. Others like to build and (re-)design more sophisticated systems by assembling the parts, i.e., genetic circuits within various topics including protein design and metabolic engineering[2]. Broadly speaking, synthetic biology is the application of engineering principles to biological science in order to conquer the highly complex behavior of living systems and harness them for the various applications (Figure 1). One of the key components in synthetic biology is to identify "parts" using genetic information, based on which new biological "devices" and "systems" can be designed and constructed[3], analogous to the way electrical and chemical engineers build circuits and chemical plants using logic gates and operation units, respectively[4,5]. However, its scope is steadily broadening and if the technology is brought to fruition, synthetic biology is expected to open up new and efficient production channels for the chemical and pharmaceutical industry to solve a number of major global challenges in various fields such as healthcare, safety, energy and environment. Hence, synthetic biology has been touted as the potential disruptive technology and has garnered a lot of attention by the global scientific community in the recent years; it is showing its increasing significance to the global economy and society. Recently, BCC Research reported that the global market size of synthetic biology will grow from US$1.1 billion in 2010 to US$10.8 billion in 2016[6].

In Singapore, biomedical research is well-supported with huge government investments and has a good track record of achievements. Several government initiated research institutes are already established, equipped with relevant research facilitates and high caliber scientists and engineers. In addition, many international biotech and biopharmaceutical giants are willing to open their new manufacturing facilities and R&D centers in Singapore, building on the pre-established research capabilities. All these factors are boosting the development of synthetic biology in a technology-focused and highly interdisciplinary milieu.

Singapore Research Institutes

The National University of Singapore (NUS) recently launched the Synthetic Biology Research Consortium[7] to consolidate NUS's existing synthetic biology efforts, bringing together an interdisciplinary team of biologists, engineers and scientists to work on synthetic biology. The Consortium is aligned with three major Faculties within NUS (Yong Loo Lin School of Medicine, Faculty of Engineering, and Faculty of Science) to present a synergistic environment for research excellence in Synthetic Biology, and it is engaged in developing tools and techniques for designing and constructing biological systems to produce various high value-added chemicals, biopharmaceuticals and nutrichemicals cost-effectively through the fermentation of renewable feedstocks. As a proof of concept, the group currently focuses on engineering the isoprenoid pathway in yeast cells and aims to produce high-value added terpenoid derivatives for therapeutic applications.

The Nanyang Technological University (NTU) also has potential experts in relevant areas such as metabolic engineering and structural biology, and shows strong interest in synthetic biology for applications such as biochemicals production, biosensors and food. They announced the NTU Centre for Synthetic Biology[8], which consists of various faculties from the School of Chemical and Biomedical Engineering (SCBE), School of Biological Sciences (SBS) and School of Materials Science and Engineering (MSE). The center is also trying to establish international collaborative links with Imperial College London and University of Illinois at Urbana Champaign in the related areas.

As the flagship of Singapore's research organizations, Agency for Science, Technology and Research (A*STAR) runs a Biomass-To-Chemicals Program, to build relevant capabilities to target the derivation of specific, high value chemicals (e.g. acrylic acid, adipic acid, butadiene, lactic acid) from biorenewable feedstocks such as lignocellulose. The broad range of expertise in several institutes of Biomedical Research Council (BMRC) can also contribute towards synthetic biology research in a variety of areas including the synthesis of biomimetic compounds and materials, pharmaceuticals, consumer products and bio-fuels, using tools such as chemical biology, materials chemistry, DNA technologies, engineered genetics, molecular devices, and bioinformatics. For example, Bioprocessing Technology Institute (BTI) directed by Professor Kong Peng Lam, is currently developing a "Mammalian Systems and Synthetic Biotechnology" platform for biologics application.

Limited Industry Activity

Industry activity in synthetic biology in Singapore is presently limited.Notably, Life Technologies (now part of Thermo Fisher Scientific) operates a research and development center for BIO-CAD, its proprietary software that simulates synthetic biology experiments. Singapore is continuing to attract targeted industry investments in synthetic biology as well as company activities in platform technologies development and biological design and downstream vertical applications.

Research Projects

There are some synthetic biology-themed research projects going on in Singapore. The key research focuses are metabolic and pathway engineering for the production of value-added chemicals, biomaterials, pharmaceuticals, which are too complicated, expensive or impossible by conventional chemical or engineering processes. In this regard, our group[9] aims to establish a holistic and integrative framework where three major research components including systems biology, bioinformatics and synthetic biology are incorporated. In the past years, we have been developing customizable synthetic biology platforms towards designing artificial genetic components and recombinant fusion proteins[10] as well as reconstructing and designing metabolic pathways in microbial/plant/mammalian hosts by using in silico genome-scale modeling and bioinformatics analysis to produce high value-added biochemical compounds at the industrial level[11]. More recently, our group has developed a computational codon optimization tool for efficient expression of synthetic genes in these hosts[12, 13]. Another interesting example is the application of synthetic biology to develop engineered microbes for sensing and killing a targeted human pathogen[14], as illustrated by Professor Matthew Chang in NUS. His lab has expertise in assembling genetic circuits to design microbial systems that perform programmable functions for diverse applications such as infection treatment, functional probiotic development, and biochemical production. Of course, many other Singapore-based groups are working in synthetic biology and even more groups are joining this exciting field.

Limited Funding Sources

Despite such achievements, the current main issue faced is limited funding sources to support the progress of synthetic biology activities on this island. Potential funding sources include National Medical Research Council and National Environment Agency, in addition to A*STAR. Singapore Economic Development Board (EDB) is also developing and validating strategy plans which will ultimately be used to promote industrial development in the fields of synthetic biology. Apart from that, several local and international symposiums have been organized in Singapore, such as the International Symposium on Synthetic Biology (18-19 Oct 2010), the NRF-EDB Synthetic Biology Workshop (6 Dec 2013, organized by NUS) and, more recently, the UK-Singapore workshop on Synthetic Biology (18-19 Feb 2014, jointly organized by UK Science and Innovation Network, NUS and NTU).

Conclusion

Therefore, Singapore is endeavoring to establish synthetic biology as a nation-wide research program that is aligned with industry development efforts. The key industries advancing synthetic biology will also establish economic stalwarts in Singapore: biomedical sciences, consumer business, natural resources, nutrition, biologics and clean technologies. It is foreseeable that more achievements will be obtained in this field and more businesses or even new industries will be created out of the commercialization of relevant research findings, which is likely to have profound implications for the future of the Singapore’s economy. In conclusion, Singapore will play an important role in leading synthetic biology research in Asia, and as a commercialization launch pad for businesses looking to exploit their technologies in this region.

About the Authors

Dr. Dong-Yup Lee is an assistant professor in the Department of Chemical and Biomolecular Engineering at the National University of Singapore and leads the Bioinformatics group at the Bioprocessing Technology Institute, A*STAR. His research interests include Systems Biology/Biotechnology/Bioinformatics, Synthetic and Engineering Biology, and Drug and Disease Modelling.

 

Dr. Kai Yu obtained his PhD from Zhejiang University in China in the year of 2013. Following his doctoral work in the area of protein engineering, he then pursued his research interests in protein synthetic biology while doing his post-doctoral work in the Systems Biology and Bioinformatics Group led by Dr. Dong-Yup Lee.

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