Sang+Yup+Lee
-
Distinguished Professor Lee Receives 2018 George Washington Carver Award
(Distinguished Professor Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will become the 11th recipient of the George Washington Carver Award. The award ceremony will be held during the 2018 Biotechnology Innovation Organization (BIO) World Congress on Industrial Biotechnology from July 16 through 19 at the Pennsylvania Convention Center in Philadelphia.
The annual Carver award recognizes an individual who has made a significant contribution to building the bio-based economy by applying industrial biotechnology to create environmentally sustainable products. It serves as a lasting memorial to the original vision of George Washington Carver who, over a century ago, pioneered bio-based products, materials, and energy derived from renewable agricultural feedstock. Previous recipients include the founder and CEO of POET Jeff Broin, the CEO of DuPont Ellen Kullman, and Professor Gregory Stephanopoulos at MIT.
Professor Lee is a pioneering scholar of systems metabolic engineering, leveraging technology to develop microbial bioprocesses for the sustainable and environment-friendly production of chemicals, fuels, and materials from non-food renewable biomass. He also serves as the dean of the multi-and interdisciplinary research center hub, KAIST Institute.Through his work, Professor Lee has garnered countless achievements, including being one of only 13 people in the world elected as a foreign member of both the National Academy of Sciences USA and the National Academy of Engineering USA.
He has actively promoted the importance of industrial biotechnology through engagement with the public, policymakers, and decision makers around the world. He currently serves as the co-chairman of the Global Future Council on Biotechnology for the World Economic Forum and served as the Chairman of the Emerging Technologies Council and Biotechnology Council for the World Economic Forum.
Upon the award announcement, Dr. Brent Erickson, executive vice president of BIO’s Industrial & Environmental Section lauded Professor Lee’s achievement, saying “Dr. Lee has advanced the bio-based economy by developing innovative products and processes that are sustainable and environmentally friendly. In doing so, he has become a leader in advocating on the importance of industrial biotechnology. His contributions to the advancement of the industry are a continuation of the legacy left behind by George Washington Carver.”
Professor Lee thanked his research team who has worked together for the past few decades, adding, “Industrial biotechnology is becoming increasingly important to help achieve the UN’s Sustainable Development Goals. We should continue to work together to advance the field and establish a solid foundation for the sustainable future.”
The George Washington Carver Award is sponsored by the Iowa Biotechnology Association. Joe Hrdlicka, executive director of the Iowa Biotechnology Association, said, “Dr. Sang Yup Lee’s significant contributions to the advancement of industrial biotechnology make him the perfect recipient for the George Washington Carver Award. Having published more than 575 peer-reviewed papers, contributed to 82 books, and holding 636 patents, the culmination of Dr. Lee’s work has led to the establishment of sustainable systems for bio-based production of chemicals, fuels, and materials, thus reducing environmental impact and improving quality of life for all.”
2018.07.12 View 4827 -
P.V. Danckwerts Memorial Lecture Awards Distinguished Professor Lee
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering was selected as the awardee of the 2018 P.V. Danckwerts Memorial Lecture.
Professor Lee was named the recipient in recognition of his distinguished achievements developing innovative eco-friendly and sustainable chemical materials by applying metabolic engineering. The award is co-sponsored by the Chemical Engineering Science, the Institute of Chemical Engineers, the American Institute of Chemical Engineers, and the European Federation of Chemical Engineering.
The award ceremony and Professor Lee’s lecture will be held at the annual meeting of the American Institute of Chemical Engineers in October in Pittsburgh, PA in the US. He will give a lecture titled “Biotechnology to Help Achieve the UN’s Sustainable Development Goals.”
The P.V. Danckwerts Lecture was established in 1985 in honor of Professor Peter V. Danckwerts at the University of Cambridge who made significant contributions to the chemical engineering field. Professor Danckwerts served as executive editor of the Chemical Engineering Science and the president of the Institute of Chemical Engineers.
Professor Lee, currently the dean of KAIST Institutes, a multi-and interdisciplinary convergence research center, is taking the lead in biotechnology, especially in the field of metabolic engineering.
Professor Lee’s research team’s novel approaches have been gaining notable attention in the sustainable chemical engineering field and future health care innovations. His team recently presented research on drug-drug and drug-food interactions by using AI, a recombinant E.coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table, bio-degradable aromatic polymer’s enzyme production, and a molecular mechanism for PET degradation.
With this award, Professor Lee joined other prominent recipients including Dr. Neal Amundson at the University of Houston, the late Professor Octave Levenspiel at Oregon State University, and Professor Rutherford Aris at the University of Minnesota. Professor Lee is the second Asian recipient, following Dr. Mooson Kwauk at the Institute of Process Engineering of the Chinese Academy of Sciences who won the lecture award in 1989.
2018.06.18 View 3148 -
Recombinant E. Coli As a Biofactory for the Biosynthesis of Diverse Nanomaterials
(Distinguished Professor Lee and PhD candidate Choi)
A metabolic research group at KAIST and Chung-Ang University in Korea has developed a recombinant E. coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table. Among the elements, the team could biosynthesize 33 novel nanomaterials for the first time, advancing the forward design of nanomaterials through the biosynthesis of various single and multi-elements.
The study analyzed the nanomaterial biosynthesis conditions using a Pourbaix diagram to predict the producibility and crystallinity. Researchers studied a Pourbaix diagram to predict the stable chemical species of each element for nanomaterial biosynthesis at varying levels of reduction potential (Eh) and pH. Based on the Pourbaix diagram analyses, the initial pH of the reaction was changed from 6.5 to 7.5, resulting in the biosynthesis of various crystalline nanomaterials that were previously amorphous or not synthesized.
This strategy was extended to biosynthesize multi-element nanomaterials. Various single and multi-element nanomaterials biosynthesized in this research can potentially serve as new and novel nanomaterials for industrial applications such as catalysts, chemical sensors, biosensors, bioimaging, drug delivery, and cancer therapy.
A research group consisting of PhD candidate Yoojin Choi, Associate Professor Doh Chang Lee, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST and Associate Professor Tae Jung Park of the Department of Chemistry at Chung-Ang University reported the synthesis. This study, entitled “Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials,” was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on May 21.
A recent successful biosynthesis of nanomaterials under mild conditions without requiring physical and chemical treatments has triggered the exploration of the full biosynthesis capacity of a biological system for producing a diverse range of nanomaterials as well as for understanding biosynthesis mechanisms for crystalline versus amorphous nanomaterials.
There has been increased interest in synthesizing various nanomaterials that have not yet been synthesized for various applications including semiconducting materials, enhanced solar cells, biomedical materials, and many others. This research reports the construction of a recombinant E. coli strain that co-expresses metallothionein, a metal binding protein, and phytochelatin synthase that synthesizes the metal-binding peptide phytochelatin for the biosynthesis of various nanomaterials. Subsequently, an E. coli strain was engineered to produce a diverse range of nanomaterials, including those never biosynthesized before, by using 35 individual elements from the periodic table and also by combining multi-elements.
Distinguished Professor Lee said, “An environmentally-friendly and sustainable process is of much interest for producing nanomaterials by not only chemical and physical methods but biological synthesis. Moreover, there has been much attention paid to producing diverse and novel nanomaterials for new industrial applications. This is the first report to predict the biosynthesis of various nanomaterials, by far the largest number of various single- and multi-elements nanomaterials. The strategies used for nanomaterial biosynthesis in this research will be useful for further diversifying the portfolio of nanomaterials that can be manufactured.”
Figure: The biosynthesis of diverse nanomaterials using recombinant E. coli. This schematic diagram shows the overall conceptualization of the biosynthesis of various single and multi-element nanomaterials using recombinant E. coli under incubation with corresponding elemental precursors. The 35 elements that were tested to biosynthesize nanomaterials are shown in black circles on the periodic table.
2018.05.23 View 6989 -
Cross-Generation Collaborative Labs Open
KAIST opened two cross-generation collaborative labs last month. This novel approach will pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires.
This is one of the Vision 2031 innovation initiatives established to extend the spectrum of knowledge and research competitiveness. The selected labs will be funded for five years and the funding will be extended if necessary. KAIST will continue to select new labs every year.
A five-member selection committee including the Nobel Laureates Professor Klaus Von Klitzing at the Max-Planck Institute for Solid State Research and Dr. Kurt Wüthrich from ETH Zürich selected the first two labs with senior-junior pairs in March.
(Two renowned scholars' Cross-Generation Collaborative Labs which opened last month.
Distinguished Professor Lee's lab (above) andChair Professor Sung's lab)
Both labs are run by world-renowned scholars: the Systems Metabolic Engineering and Systems Healthcare Laboratory headed by Distinguished Professor Sang-Yup Lee in the Department of Chemical and Biomolecular Engineering and the Acousto-Microfluidics Research Center for Next-Generation Healthcare led by Chair Professor Hyung Jin Sung in the Department of Mechanical Engineering.
Distinguished Professor Lee will be teamed up with Professor Hyun Uk Kim, and their lab aims to mass produce new eco-friendly chemical materials as well as higher-value-added materials which will be used for medicine. The new platform technologies created in the lab are expected to provide information which will benefit human healthcare.
Meanwhile, the Acousto-Microfluidics Research Center for Next-Generation Healthcare will team up with Professors Hyoungsoo Kim and Yeunwoo Cho under Chair Professor Sung. The lab will conduct research on controlling fluids and objects exquisitely on a micro-nano scale by using high-frequency acoustic waves. The lab plans to develop a next-generation healthcare platform for customized diagnoses as well as disease treatment.
KAIST President Sung-Chul Shin, who introduced this novel idea in his research innovation initiative, said that he hopes the Cross-Generation Collaborative Labs will contribute to honoring senior scholars’ research legacies and passing knowledge down to junior researchers in order to further develop their academic achievements. He said, “I sincerely hope the labs will make numerous research breakthroughs in the very near future.”
2018.05.03 View 5013 -
Deep Learning Predicts Drug-Drug and Drug-Food Interactions
A Korean research team from KAIST developed a computational framework, DeepDDI, that accurately predicts and generates 86 types of drug-drug and drug-food interactions as outputs of human-readable sentences, which allows in-depth understanding of the drug-drug and drug-food interactions.
Drug interactions, including drug-drug interactions (DDIs) and drug-food constituent interactions (DFIs), can trigger unexpected pharmacological effects, including adverse drug events (ADEs), with causal mechanisms often unknown. However, current prediction methods do not provide sufficient details beyond the chance of DDI occurrence, or require detailed drug information often unavailable for DDI prediction.
To tackle this problem, Dr. Jae Yong Ryu, Assistant Professor Hyun Uk Kim and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at Korea Advanced Institute of Science and Technology (KAIST), developed a computational framework, named DeepDDI, that accurately predicts 86 DDI types for a given drug pair. The research results were published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 16, 2018, which is entitled “Deep learning improves prediction of drug-drug and drug-food interactions.”
DeepDDI takes structural information and names of two drugs in pair as inputs, and predicts relevant DDI types for the input drug pair. DeepDDI uses deep neural network to predict 86 DDI types with a mean accuracy of 92.4% using the DrugBank gold standard DDI dataset covering 192,284 DDIs contributed by 191,878 drug pairs. Very importantly, DDI types predicted by DeepDDI are generated in the form of human-readable sentences as outputs, which describe changes in pharmacological effects and/or the risk of ADEs as a result of the interaction between two drugs in pair. For example, DeepDDI output sentences describing potential interactions between oxycodone (opioid pain medication) and atazanavir (antiretroviral medication) were generated as follows: “The metabolism of Oxycodone can be decreased when combined with Atazanavir”; and “The risk or severity of adverse effects can be increased when Oxycodone is combined with Atazanavir”. By doing this, DeepDDI can provide more specific information on drug interactions beyond the occurrence chance of DDIs or ADEs typically reported to date.
DeepDDI was first used to predict DDI types of 2,329,561 drug pairs from all possible combinations of 2,159 approved drugs, from which DDI types of 487,632 drug pairs were newly predicted. Also, DeepDDI can be used to suggest which drug or food to avoid during medication in order to minimize the chance of adverse drug events or optimize the drug efficacy. To this end, DeepDDI was used to suggest potential causal mechanisms for the reported ADEs of 9,284 drug pairs, and also predict alternative drug candidates for 62,707 drug pairs having negative health effects to keep only the beneficial effects. Furthermore, DeepDDI was applied to 3,288,157 drug-food constituent pairs (2,159 approved drugs and 1,523 well-characterized food constituents) to predict DFIs. The effects of 256 food constituents on pharmacological effects of interacting drugs and bioactivities of 149 food constituents were also finally predicted. All these prediction results can be useful if an individual is taking medications for a specific (chronic) disease such as hypertension or diabetes mellitus type 2.
Distinguished Professor Sang Yup Lee said, “We have developed a platform technology DeepDDI that will allow precision medicine in the era of Fourth Industrial Revolution. DeepDDI can serve to provide important information on drug prescription and dietary suggestions while taking certain drugs to maximize health benefits and ultimately help maintain a healthy life in this aging society.”
Figure 1. Overall scheme of Deep DDDI and prediction of food constituents that reduce the in vivo concentration of approved drugs
2018.04.18 View 6881 -
Structural Insight into the Molecular Mechanism of PET Degradation
A KAIST metabolic engineering research team has newly suggested a molecular mechanism showing superior degradability of poly ethylene terephthalate (PET).
This is the first report to simultaneously determine the 3D crystal structure of Ideonella sakaiensis PETase and develop the new variant with enhanced PET degradation.
Recently, diverse research projects are working to address the non-degradability of materials. A poly ethylene terephthalate (PET)-degrading bacterium called Ideonella sakaiensis was recently identified for the possible degradation and recycling of PET by Japanese team in Science journal (Yoshida et al., 2016). However, the detailed molecular mechanism of PET degradation has not been yet identified.
The team under Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and the team under Professor Kyung-Jin Kim of the Department of Biotechnology at Kyungpook National University conducted this research. The findings were published in Nature Communications on January 26.
This research predicts a special molecular mechanism based on the docking simulation between PETase and a PET alternative mimic substrate. Furthermore, they succeeded in constructing the variant for IsPETase with enhanced PET-degrading activity using structural-based protein engineering.
It is expected that the new approaches taken in this research can be background for further study of other enzymes capable of degrading not only PET but other plastics as well.
PET is very important source in our daily lives. However, PET after use causes tremendous contamination issues to our environment due to its non-biodegradability, which has been a major advantage of PET. Conventionally, PET is disposed of in landfills, using incineration, and sometimes recycling using chemical methods, which induces additional environmental pollution. Therefore, a new development for highly-efficient PET degrading enzymes is essential to degrade PET using bio-based eco-friendly methods.
Recently, a new bacterial species, Ideonella sakaiensis, which can use PET as a carbon source, was isolated. The PETase of I. sakaiensis (IsPETase) can degrade PET with relatively higher success than other PET-degrading enzymes. However, the detailed enzyme mechanism has not been elucidated, hindering further studies.
The research teams investigated how the substrate binds to the enzyme and which differences in enzyme structure result in significantly higher PET degrading activity compared with other cutinases and esterases, which make IsPETase highly attractive for industrial applications toward PET waste recycling.
Based on the 3D structure and related biochemical studies, they successfully predicted the reasons for extraordinary PET degrading activity of IsPETase and suggested other enzymes that can degrade PET with a newly-classified phylogenetic tree. The team proposed that 4 MHET moieties are the most properly matched substrates due to a cleft on structure even with the 10-20-mers for PET. This is meaningful in that it is the first docking simulation between PETase and PET, not its monomer.
Furthermore, they succeeded in developing a new variant with much higher PET-degrading activity using a crystal structure of this variant to show that the changed structure is better to accommodate PET substrates than wild type PETase, which will lead to developing further superior enzymes and constructing platforms for microbial plastic recycling.
Professor Lee said, “Environmental pollution from plastics remains one of the greatest challenges worldwide with the increasing consumption of plastics. We successfully constructed a new superior PET-degrading variant with the determination of a crystal structure of PETase and its degrading molecular mechanism. This novel technology will help further studies to engineer more superior enzymes with high efficiency in degrading. This will be the subject of our team’s ongoing research projects to address the global environmental pollution problem for next generation.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation of Korea. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930)
(Figure: Structural insight into the molecular mechanism of poly(ethylene terephthalate) degradation and the phylogenetic tree of possible PET degrading enzymes. This schematic diagram shows the overall conceptualization for structural insight into the molecular mechanism of poly (ethylene terephthalate) degradation and the phylogenetic tree of possible PET degrading enzymes.)
2018.01.31 View 5827 -
One-Step Production of Aromatic Polyesters by E. coli Strains
KAIST systems metabolic engineers defined a novel strategy for microbial aromatic polyesters production fused with synthetic biology from renewable biomass. The team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering produced aromatic polyesters from Escherichia coli (E. coli) strains by applying microbial fermentation, employing direct microbial fermentation from renewable feedstock carbohydrates.
This is the first report to determine a platform strain of engineered E. coli capable of producing environmentally friendly aromatic polyesters. This engineered E. coli strain, if desired, has the potential to be used as a platform strain capable of producing various high-valued aromatic polyesters from renewable biomass. This research was published in Nature Communications on January 8.
Conventionally, aromatic polyesters boast solid strength and heat stability so that there has been a great deal of interest in fermentative production of aromatic polyesters from renewable non-food biomass, but without success.
However, aromatic polyesters are only made by feeding the cells with corresponding aromatic monomers as substrates, and have not been produced by direct fermentation from renewable feedstock carbohydrates such as glucose.
To address this issue, the team prescribed the detailed procedure for aromatic polyester production through identifying CoA-transferase that activates phenylalkanoates into their corresponding CoA derivatives. In this process, researchers employed metabolic engineering of E. coli to produce phenylalkanoates from glucose based on genome-scale metabolic flux analysis. In particular, the KAIST team made a modulation of gene expression to produce various aromatic polyesters having different monomer fractions.
The research team successfully produced aromatic polyesters, a non-natural polymer using the strategy that combines systems metabolic engineering and synthetic biology. They succeeded in biosynthesis of various kinds of aromatic polyesters through the system, thus proving the technical excellence of the environmentally friendly biosynthetic system of this research. Furthermore, his team also proved the potential of expanding the range of aromatic polyesters from renewable resources, which is expected to play an important role in the bio-plastic industry.
Professor Lee said, “An eco-friendly and sustainable chemical industry is the key global agenda every nation faces. We are making a research focus to a biochemical industry free from petroleum dependence, and conducting diverse research activities to address the issue. This novel technology we are presenting will serve as an opportunity to advance the biochemical industry moving forward.”
This work was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) and also by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation of Korea.
Figure: Biosynthesis of aromatic polyesters by metabolically engineered E. coli.This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced aromatic polyesters from glucose.
2018.01.09 View 4754 -
Distinguished Professor Sang Yup Lee Named NAI Fellow
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering was named to the National Academy of Inventors in the US. He is the first Korean scholar ever elected as a NAI fellow.
The NAI is a non-profit member organization with over 4,000 individual inventors and fellows spanning more than 250 institutions worldwide. It is comprised of universities as well as governmental and non-profit research institutes. The academy was founded in 2010 to recognize and encourage inventors with patents from the US Patent and Trademark Office. So far, 575 fellows from 229 institutions have been elected.
The academy said Professor Lee has been recognized for fellowship induction as he has demonstrated a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development, and the welfare of society.
Distinguished Professor Lee, a pioneering researcher and scholar in the field of systems metabolic engineering, was ranked in the top 1% of highly cited researchers (HCR) this year. Over the past 11 years, he published more than 130,000 articles in prestigious journals around the world. He has been cited more than 34,000 times since he started working at KAIST in 1994.
He is also the first Korean ever elected to both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US, becoming the one of 13 foreign scholars in the world holding two prestigious institutions’ fellowships.
Dr. Lee is currently the dean of KAIST Institutes, the world-leading institute for multi and interdisciplinary research. He is also serving as co-chair of the Global Council on Biotechnology and is a member of the Global Future Council on the Fourth Industrial Revolution at the World Economic Forum.
2017.12.13 View 4121 -
In Jin Cho Earned the Best Poster Prize at ME Summit 2017
In Jin Cho, a Ph.D. student in the Department of Chemical and Biomolecular Engineering at KAIST received the best poster prize at the International Metabolic Engineering Summit 2017 held on October 24 in Beijing, China.
The International Metabolic Engineering Summit is a global conference where scientists and corporate researchers in the field of metabolic engineering present their latest research outcomes and build networks.
At this year’s summit, about 500 researchers from around the world participated in active academic exchanges, including giving keynote speeches and presenting posters.
During the poster session, the summit selects one person for the KeAi-synthetic and Systems Biotechnology Poster Award, two for Microbial Cell Factories Poster Awards, and three for Biotechnology Journal Poster Awards among the posters presented by graduate students, post-doctoral fellows and researchers. Cho received the KeAi-synthetic and Systems Biotechnology Poster Award. Her winning poster is on the biotransformation of p-xylene to terephthalic acid using engineered Escherichia coli.
Terephthalic acid is generally produced by p-xylene oxidation; however, this process requires a high temperature and pressure as well as a toxic catalyst during the reaction process.
Cho and Ziwei Luo, a Ph.D. student at KAIST, co-conducted the research and developed a successful biological conversion process. Compared to the existing chemical process, it does not require a high temperature and pressure; and it is environmentally friendly with a relatively high conversion rate of approximately 97%.
Cho’s advisor, Distinguished Professor Sang Yup Lee said, “Further research on glucose-derived terephthalic acid will enable us to produce biomass-based eco-friendly terephthalic acid through engineered Escherichia coli.”
2017.10.31 View 4270 -
Distinguished Professor Lee Named International Fellow of the CAS
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST was awarded the title of distinguished professor and international fellow from the Chinese Academy of Sciences (CAS), and honorary professor from its affiliated organization the Tianjin Institute of Industrial Biotechnology (TIB).
The CAS recognized Distinguished Professor Lee for his significant contributions to biotechnology. He has made significant pioneering academic achievements in the area of systems metabolic engineering, which produces useful chemicals from microorganisms. Not only did he develop the first and best source technology in that field, but also came out with processes for the production of biofuel and environmentally-friendly chemicals.”
As a global leader in systems metabolic engineering, Distinguished Professor Lee has also been appointed as an honorary professor at Jiangnan University in Wuxi, China.
Distinguished Professor Lee was listed in the ‘Top 20 Translational Researchers of 2014’ selected by the renowned international journal Nature Biotechnology. Moreover, he was the first Asian recipient of the James E. Bailey Award in 2016 and Marvin J. Johnson Award in 2012, which are given to scholars in the field of biotechnology.
He is also one of 13 global scientists who are foreign members of the renowned academic societies the National Academy of Engineering and the National Academy of Sciences in the US. Furthermore, he received the ‘2017 Korea Best Scientist Award’ from the president of Korea in July. Finally, his founding field, systems metabolic engineering, was chosen as one of the ‘Top 10 Emerging Technologies of 2016’ by the World Economic Forum.
The Chinese Academy of Sciences, established in November 1949, is an academic organization that carries out research on basic sciences and natural sciences in China. It defined its science and technology system to include the fields of basic sciences, natural sciences, and high technology. While having a base in Beijing, its branch academies are located in 12 main cities along with 117 affiliates and 100 national key labs.
2017.10.26 View 5198 -
Development of a Highly-Accurate Computational Model of Human Metabolism
A research team from KAIST developed a computational framework that enables the reconstruction of a comprehensive computational model of human metabolism, which allows for an accurate prediction of personal metabolic features (or phenotypes).
Understanding personal metabolic phenotypes allows us to design effective therapeutic strategies for various chronic and infectious diseases. A human computational model called the genome-scale metabolic model (GEM) contains information on thousands of metabolic genes and their corresponding reactions and metabolites, and has played an important role in predicting metabolic phenotypes. Although several versions of human GEMs have been released, they had room for further development, especially as to incorporating biological information coming from a human genetics mechanism called “alternative splicing.” Alternative splicing is a genetic mechanism that allows a gene to give rise to multiple reactions, and is strongly associated with pathology.
To tackle this problem, Jae Yong Ryu (a Ph.D. student), Dr. Hyun Uk Kim (Research Fellow), and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at KAIST, developed a computational framework that systematically generates metabolic reactions, and adds them to the human GEM. The resulting human GEM was demonstrated to accurately predict metabolic phenotypes under varied environmental conditions. The research results were published online in Proceedings of the National Academy of Sciences (PNAS) on October 24, 2017, under the title “Framework and resource for more than 11,000 gene-transcript-protein-reaction associations in human metabolism.”
The research team first updated the biological contents of a previous version of the human GEM. The updated biological contents include metabolic genes and their corresponding metabolites and reactions. In particular, metabolic reactions catalyzed by already-known protein isoforms were additionally incorporated into the human GEM; protein isoforms are multiple variants of proteins generated from individual genes through the alternative splicing process. Each protein isoform is often responsible for the operation of a metabolic reaction. Although multiple protein isoforms generated from one gene can play different functions by having different sets of protein domains and/or subcellular localizations, such information was not properly considered in previous versions of human GEMs.
Upon the initial update of the human GEM, named Recon 2M.1, the research team subsequently implemented a computational framework that systematically generates information on Gene-Transcript-Protein-Reaction Associations (GeTPRA) in order to identify protein isoforms that were previously not identified. This framework was developed in this study. As a result of the implementation of the framework for GeTPRA, more than 11,000 GeTPRA were automatically predicted, and thoroughly validated. Additional metabolic reactions were then added to Recon 2M.1 based on the predicted GeTPRA for the previously uncharacterized protein isoforms; Recon 2M.1 was renamed Recon 2M.2 from this upgrade.
Finally, Recon 2M.2 was integrated with 446 sets of personal biological data (RNA-Seq data) in order to build patient-specific cancer models. These patient-specific cancer models were used to predict cancer metabolism activities and anticancer targets.
The development of a new version of human GEMs along with the computational framework for GeTPRA is expected to boost studies in fundamental human genetics and medicine. Model files of the human GEMs Recon 2M.1 and 2M.2, a full list of the GeTPRA and the source code for the computational framework to predict the GeTPRA are all available as part of the publication of this study.
Distinguished Professor Lee said, “The predicted GeTPRA from the computational framework is expected to serve as a guideline for future experiments on human genetics and biochemistry, whereas the resulting Recon 2M.2 can be used to predict drug targets for various human diseases.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.
(Figure 1:A scheme of Recon 2M.1 development and its use in reconstructing personal genome-scale metabolic models (GEMs). (A) A concept of alternative splicing of human genes and its use in Gene-Transcript-Protein-Reaction Associations (GeTPRA) of Recon 2M.1. (B) A procedure of systematic refinement of the Recon 2Q. Recon 2Q is one of the previously released human GEMs. Biochemically inconsistent reactions include unbalanced, artificial, blocked, and/or redundant reactions. Iterative manual curation was conducted while validating the Recon 2M.1. (C) Reconstruction of cancer patient-specific GEMs using Recon 2M.1 for further simulation studies. In this study, personal biological data (RNA-Seq data) were obtained from The Cancer Genome Atlas (TCGA; https://cancergenome.nih.gov/ ) across the ten cancer types.
(Figure 2: Computational framework for the systematic generation of Gene-Transcript-Protein-Reaction Associations (GeTPRA; red box in the flowchart). Peptide sequences of metabolic genes defined in Recon 2M.1 were retrieved from a database called Ensembl. EC numbers and subcellular localizations of all the protein isoforms of metabolic genes in Recon 2M.1 were predicted using software programs EFICAz2.5 and Wolf PSort, respectively. Information on the newly predicted GeTPRA was systematically incorporated into the Recon 2M.1, thereby resulting in Recon 2M.2.)
2017.10.25 View 5717 -
KAIST-WEF Roundtable on Inclusive Growth and Job Creation
The World Economic Forum (WEF) will join KAIST in an effort to address sweeping global problems in the wake of the Fourth Industrial Revolution. The two will co-host a roundtable on ‘Shaping Korea’s Priorities for Inclusive Growth and Job Creation in the Fourth Industrial Revolution’ on October 13 at Lotte Hotel in Seoul.
The roundtable will bring together leaders from government, industry, universities, and non-profit civic organizations to have an in-depth discussion on a thought-provoking agenda of inclusive growth and job creation which scientific and technological changes will bring about. The event will provide a platform to explore practical collaboration and innovative strategies for better job creation and innovation ecosystems.
The two will also sign an MOU for collaboration between the Fourth Industrial Revolution Information Center (FIRIC) of KAIST and the WEF Center for the Fourth Industrial Revolution (C4IR).
President Sung-Chul Shin of KAIST and the Head of the WEF Center for the Fourth Industrial Revolution, Murat Sonmez, will lead the panel discussion titled ‘Inclusive Growth and the Fourth Industrial Revolution’ which will be attended by leaders from government, industry, and non-profit civic organizations.
At the breakout sessions, the topics will be “Future Jobs” and the “Creation of Innovation Ecosystems”. Additionally, a discussion on the “SME 4.0 Initiative”, which is a program pushed forward by KAIST in collaboration with local governments, will talk about job creation through innovation in small and medium-sized enterprises (SMEs). The WEF will introduce their two-year activities and research on the Fourth Industrial Revolution, which have great potential and a high possibility of successfully undergoing the revolution, to Korea.
Since WEF Executive Chairman Klaus Schwab brought up the topic of the Fourth Industrial Revolution, the WEF has been leading agenda topics and discussions on high-profile matters, including ‘technology-driven but human-centered inclusive growth’ in predicting the future of jobs.
The WEF is a nonprofit organization committed to addressing the world’s weightiest problems. It is best known for its annual meetings in Davos, Switzerland, which attracts leaders from around the world. KAIST has been participating in this summit since 2009. President Shin will also attend the upcoming Davos summit next January. Distinguished Professor Sang Yup Lee who heads the KAIST Institute and the FIRIC is the co-chair of the Global Council on Biotechnology and a member of the Global Future Council on the Fourth Industrial Revolution at the WEF.
Moreover, President Shin and Mr. Sonmez will explain the background of the roundtable and share the results of the sessions at a joint news conference.
2017.09.28 View 5529