Synthetic Biology

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Faculty

Platform Technology
Prof. Chueh Loo’s lab has the capabilities to design and construct biological genetic circuits (e.g. sensors, logic gates etc) for the engineering of microbes for useful applications. In addition it can be used for. high throughput characterization of standard genetic circuits and systems, computational modeling of genetic circuits for circuits optimization, and development of computer aided design tools for complex genetic circuit design. Our expertise lies in synthetic and system biology, microbial engineering, computer aided genetic circuit design, computational biology, and informatics.
Prof. Jiang Rongrong’s group is the first to use directed evolution methods to engineer global transcription factor CRP of E. coli to improve its performance under various stresses during bioprocessing. Her recent publication on strain transcriptional engineering during biofuel production (Biotech. Bioeng. 2012) has been selected for video abstract by Biotech & Bioeng, and highlighted by “Global Medical Discovery” as key scientific article. Her group is the first to use directed evolution methods to engineer global transcription factor CRP of E. coli to improve its performance under various stresses during bioprocessing.


Biosynthesis of high value added chemicals and biologics
Prof. Song Hao focuses on rational genetic engineering taken from Synthetic Biology, aiming at applications in Biosynthesis of chemicals (drugs, nutraceuticals), and renewable energy (focusing on microbial electrosynthesis, and bioelectricity).
James P. Tam is the Director of the Drug Discovery Laboratory at Nanyang Technological University, Singapore. He was the founding dean of the School of Biological Sciences, founding director of the double-degree program in Biomedical Science and Chinese Medicine, and the founding director of NTU Biological Research Center. His research focuses on synthetic methodology, drug design of metabolic-stable peptidyl biologics and intracellular delivery of peptides. He developed peptide dendrimers as synthetic vaccines. His current research also includes herbalomics in traditional medicines to discover novel peptides as potential therapeutics. He received his Ph.D. in Medicinal Chemistry from the University of Wisconsin, Madison, USA and held appointments as Associate Professor at The Rockefeller University, USA (1982-1991), Professor at Vanderbilt University, USA (1991-2004) and The Scripps Research Institute, USA (2004-2008). Professor Tam has published more than 330 papers in these areas of research. He received the Vincent du Vigneaud Award in 1986, the Rao Makineni Award by American Peptide Society in 2003, the Ralph F. Hirschmann Award by the American Chemical Society (ACS) in 2005, and the Merrifield Award by American Peptide Society in 2013 for his outstanding contributions to peptide and protein sciences. In addition to his scientific research, he has also been active in the peptide community. Besides serving on many editorial boards, he organized international peptide and protein symposia and was co-founder of the past ten International Chinese Peptide Symposia. He received the Cathay Award from the Chinese Peptide Society, China in 1996.

Prof Par Nordlund and Tobias Cornvik work on a high throughput protein production platform at the School of Biological Sciences at the Nanyang Technological University. The platform is using state of the art technologies and is arguably one of the leading platforms in the world when it comes to the number and breadth of the collaborators it has work with. To date the platform has collaborated with/served more than 50 research groups at NTU, A*STAR and NUS. More than 9000 different protein constructs have been clone and over 1800 protein batches have been delivered to the customers. The proteins have been used for a wide range of applications such as structural biology, enzymatic assays, drug development and antibody generation. The platform has an average throughput of screening 200 expression constructs/month and 50+ purifications/month, enough to serve additional projects e.g. synthetic biology and commercial entities. So far the platform has had a great impact of the biomedical research community in Singapore, enabling researchers to address a much wider range of targets/proteins as compared to if the researchers would have had to produce the proteins themselves, We strongly believe that the platform will have a similar impact for the synthetic biology community.

Prof. William Chen received his PhD training in yeast genetic engineering with the world authority in the field, Prof. Andre Goffeau. He has demonstrated research track record in microbial engineering. His group aims to metabolically engineer the yeast Saccharomyces cerevisiae for enhanced biofuel precursor production. To this end, S. cerevisiae was metabolically engineered for cytosol acetyl-CoA enhancement for fatty acid synthesis. By gene disruption strategy, idh1, 2 genes involved in citrate turnover in TCA cycle were deleted and the citrate production level was increased to 4- and 5- times in mutant yeast strains. They also aim to build a whole-cell catalyst to produce medium chain biofuels efficiently with S. cerevisiae as producer. To this end, his team has applied an enzymatic engineering approach to synthesize aldehydes as precursor of alkanes and alkenes, mainly with the chain length of nine carbons in S. cerevisiae. Lipoxygenase (LOX) and hydroperoxide lyase (HPL) from plants are known for converting long chain fatty acids into aldehydes. Two enzymes with high specificity were exogenous expressed and accomplish the key tasks in our enzymatic engineering approach. The whole-cell catalyst described here may well be a promising approach toward efficient production of medium chain biofuels precursor. In addition, they have reengineered the β-oxidation pathway of S. cerevisiae to accumulate more fatty acids with higher medium chain fatty acids (MCFAs) ratio with fatty acid-rich feedstock. Compared with wild type (WT) strain, total fatty acids of strains △pox1 [pox2+] and △pox1 [pox2+, crot+] significantly increased. The intracellular level of MCFAs of △pox1 [pox2+] and △pox1 [pox2+, crot+] increased to 2.26 and 1.87 fold compared to the WT strain. These results suggested that fatty acids with higher MCFAs ratio can be accumulated in yeast strains with modified β-oxidation pathway. His approach has great potential in transforming low value fatty acid-rich feedstock into high value fatty acid-derived products.

Prof Liang’s lab mainly focuses on the secondary metabolic pathways that produce polyketide-derived natural products with interesting biological activities. In the last several years, they have grown into a lab with considerable expertise and knowledge in heterologous cloning, expression of microbial enzymes and mechanistic investigation of polyketide synthetic pathways. The bacterial and fungal expression systems established in the lab allow us to investigate biosynthetic pathways encoded by various microorganisms. These capabilities also equipped them well for synthetic biology-related research projects such as the engineering of microbes for the production of commercially valuable chemicals.
Prof. Thiru Thanabalu is well established in research in yeast. His lab focuses on genetic engineering S. cerevisiae to use Xylose as a carbon Source. Hemicellulose is one of the major components of renewable biomass, comprising up to 35% of plant material and Xylose is one of the major sugars present after the conversion of hemicelluloses to monosaccharides. S. cerevisiae is a non-pathogenic unicellular eukaryote with a well characterized genome. This unicellular organism has been used extensively to decipher the molecular mechanism of cell cycle and other cellular processes common to all the eukaryotes including humans. S. cerevisiae can be cultivated easily in laboratory and can be easily scale up in industrial fermentation. One of the short comings of this yeast is its inability to use five carbon sugars such as xylose which comprise as much as 30% of wood waste. The inability of this organism to utilize Xylose is probably due to its inability to transport Xylose through the six carbon transporters and also the inability of the xylose metabolic pathways in this yeast. Thus we are currently carrying out genetic engineering of this organism with Xylose transporters and xylose metabolic enzymes from other organisms. We are also currently generating mutants of S. cerevisiae by exposing the cells to UV and screening for mutants which can utilize xylose as a carbon source. We will use the xylose utilizing S. cerevisiae to generate bioethanol and alkanes.

Prof Mary Chan is interested in biocatalysis and biotransformations, particularly of polyamminosaccharides with defined amination, stereochemistries that are useful for antimicrobial compounds


Biomimetic Systems
Dr. Miserez’s research is centered on revealing the molecular, physico-chemical, and structural principles from unique biological materials, and on translating these designs into novel biomimetic synthesis strategies. His research group is strongly cross-disciplinary, with molecular biologists, chemists, biophysicists, and materials scientists combining their expertise towards bioinspired engineering from various angles, including protein biochemistry, extra-cellular tissue transcriptomics, polymer chemistry, biomimetic peptide design, biophysics, and nanomechanics. His research provides significant potential as a way to develop the next-generation of “green materials”, which is considered vital in our global sustainability efforts. Recent high profile publications include the comprehensive structure/property relationships of dactyl clubs from stomatopods (mantis shrimps), which are ultra-mineralized, impact-resistant biological “hammers” with remarkable resistance against damage (Science, vol. 336, pp. 1275- 1280, 2012). His lab also recently pioneered the integrative usage of Next Gen RNA sequencing in the context of biomaterials as a way to rapidly design novel biomimetic materials (Nature Biotechnology, vol. 31, pp. 908-15, 2013). His research on biomimetic materials has been featured in numerous popular media, including in “National Geographic”, “BBC International”, “Associated Press”, or “The New York Times”, among others. He has given numerous invited talks, including at the “Gordon Research Conferences” (GRC) and his work has been featured on the cover of various journals, including in Advanced Materials, Advanced Functional Materials, Journal of Biological Chemistry, Chemical Society Review, and Nature Biotechnology.

Prof Eileen Fong’s is interested in genetically engineering microbes found naturally in activated sludge, to increase their capacity for phosphate uptake. It is hoped that such genetically modified microbes will lead to higher efficiency and reduced costs of EPBR operations. They have successfully developed genetic methods for increasing phosphate uptake in magnetotactic bacteria (publication under review), and are currently modifying selective bacteria populations in activated sludge to increase their phosphate uptake abilities to improve the efficiency of EPBR in tropical climates.
Dr Meng How Tan has expertise in systems biology and genomics and aims to engineer genetically encoded biosensors in both microbes and mammalian cells. He is interested in understanding how the ubiquitous bacterium Caulobacter crescentus uses two-component systems and riboswitches to survive in a wide range of environmental conditions, including water contaminated with heavy metals. He is also interested in understanding how extremophiles can thrive in hostile environments like high temperatures or low pH. The goal is to utilize this knowledge to construct synthetic devices for environmental sensing and bioremediation applications. He is also interested in building sensors and other synthetic genetic circuits in mammalian cells for intelligent biopharmaceutical manufacturing, drug testing, and controlled stem cell differentiation applications.
Prof. Sierin Lim’s group combines genetic engineering and synthetic biology approaches to synthesize intracellular biological compartments and artificial pumps on the microbial membranes. Potential application of this system will be for bioremediation, water purification and toxin reduction.