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Scientist of November, Professor Hyung Jin Sung
Professor Hyung Jin Sung from the Department of Mechanical Engineering at KAIST received a ‘Science and Technology Award of the Month’ given by the Ministry of ICT and Science and the National Research Foundation of Korea for November 2017. He developed technology that can exquisitely control a micrometer-scaled liquid drop on a dime-sized lab-on-a-chip. With his work, he was recognized for reinforcing research capability on microfluidics. Lab-on-a-chip is an emerging experiment and diagnostic technology in the form of a bio-microchip that facilitates complex and various experiments with only a minimal sample size required. This technology draws a lot of attention not only from medical and pharmaceutical areas, but also the health and environmental field. The biggest problem was that technology for the temperature control of a fluid sample, which is one of the core technologies in microfluidics, has low accuracy. This limit had to be overcome in order to use the lab-on-a-chip more widely. Professor Sung developed an acoustic and thermal method which controls the temperature of a droplet quickly and meticulously by using sound and energy. This is a thermal method that uses heat generated during the absorption of an acoustic wave into viscoelastic substances. It facilitates a rapid heating rate and spatial-temporal temperature control, allowing heating in desired areas. In addition, Professor Sung applied his technology to polymerase chain reactions, which are used to amplify DNA. Through this experiment, he successfully shortened the reaction time from 1-2 hours to only three minutes, making this a groundbreaking achievement. Professor Sung said, “My research is significant for enhancing the applicability of microfluidics. I expect that it will lead to technological innovations in healthcare fields including biochemistry, medical checkups, and new medicine development.”
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.)
Semiconductor Patterning of Seven Nanometers Technology Using a Camera Flash
A research team led by Professor Sang Ouk Kim in the Department of Materials Science and Engineering at KAIST has developed semiconductor manufacturing technology using a camera flash. This technology can manufacture ultra-fine patterns over a large area by irradiating a single flash with a seven-nanometer patterning technique for semiconductors. It can facilitate the manufacturing of highly efficient, integrated semiconductor devices in the future. Technology for the Artificial Intelligence (AI), the Internet of Things (IoTs), and big data, which are the major keys for the fourth Industrial Revolution, require high-capacity, high-performance semiconductor devices. It is necessary to develop lithography technology to produce such next-generation, highly integrated semiconductor devices. Although related industries have been using conventional photolithography for small patterns, this technique has limitations for forming a pattern of sub-10 nm patterns. Molecular assembly patterning technology using polymers has been in the spotlight as the next generation technology to replace photolithography because it is inexpensive to produce and can easily form sub-10 nm patterns. However, since it generally takes a long time for heat treatment at high-temperature or toxic solvent vapor treatment, mass production is difficult and thus its commercialization has been limited. The research team introduced a camera flash that instantly emits strong light to solve the issues of polymer molecular assembly patterning. Using a flash can possibly achieve a semiconductor patterning of seven nanometers within 15 milliseconds (1 millisecond = 1/1,000 second), which can generate a temperature of several hundred degrees Celsius in several tens of milliseconds. The team has demonstrated that applying this technology to polymer molecular assembly allows a single flash of light to form molecular assembly patterns. The team also identified its compatibility with polymer flexible substrates, which are impossible to process at high temperatures. Through these findings, the technology can be applied to the fabrication of next-generation, flexible semiconductors. The researchers said the camera flash photo-thermal process will be introduced into molecular assembly technology and this highly-efficiency technology can accelerate the realization of molecular assembly semiconductor technology. Professor Kim, who led the research, said, “Despite its potential, molecular assembly semiconductor technology has remained a big challenge in improving process efficiency.” “This technology will be a breakthrough for the practical use of molecular assembly-based semiconductors.” The paper was published in the international journal, Advanced Materials on August 21 with first authors, researcher Hyeong Min Jin and PhD candidate Dae Yong Park. The research, sponsored by the Ministry of Science and ICT, was co-led Professor by Keon Jae Lee in the Department of Materials Science and Engineering at KAIST, and Professor Kwang Ho Kim in the School of Materials Science and Engineering at Pusan National University. (1. Formation of semiconductor patterns using a camera flash) (Schematic diagram of molecular assembly pattern using a camera flash) (Self-assembled patterns)
Professor Jun Ho Oh's Total Solar Eclipse Featured in the APOD, NASA
(Professor Jun Ho Oh) A video of a total solar eclipse, filmed in Warm Springs, Oregon by Professor Jun Ho Oh of the Department of Mechanical Engineering, was selected as the Astronomy Picture of the Day (APOD). APOD, is a NASA website specializing in astronomy pictures. It features astronomical observations recorded by the Hubble Space Telescope or photos taken by astronomical observers from around the world. Professor Oh is now the second Korean and the first amateur photographer whose photo was selected as the APOD. According to the website, ‘the video frames were acquired with equipment specifically designed by Jun Ho Oh to track a close-up of the Sun’s periphery during the eclipse.’ Also, Digital Photography Review (dpreview.com) introduced observation points of the eclipse in his three-minute video, including solar prominences, corona, and Baily’s beads. Professor Oh, the creator of the bipedal walking humanoid robot named Hubo, has been chasing eclipse since his first trip to Turkey in 1999. “After numerous trials and failures over the last 18 years, I was finally able to capture every single breath-taking moment of the total eclipse,” said the professor. He’s already planning for the next total eclipse in Chile on July 2, 2019. Click the link to watch the video https://apod.nasa.gov/apod/ap170912.html (#1 Photo of solar eclipse) (#2 Photo of solar eclipse)
Professor Dae-Sik Im to Head the Science, Technology and Innovation Office at the Ministry of Science & ICT
(Professor Dae-Sik Im of the Department of Biological Sciences) Professor Dae-Sik Im of the Department of Biological Sciences, a renowned molecular cell biologist, was named to head the Science, Technology and Innovation Office in the Ministry of Science and ICT on August 31. He will be responsible for the oversight of national R&D projects as well as budget deliberation. Joining the KAIST faculty in 2002, he led the Creative Research Center of Cell Division and Differentiation at KAIST. Announcing the nomination of Professor Im, Cheong Wa Dae spokesman Park Soo-Hyun said, “Professor Im will be the best person to lead the innovation of the research infrastructure system for basic research studies. We believe that his expertise and leadership will make a significant impact in enhancing the nation’s science and technology competitiveness. This vice minister position in the Ministry of Science and ICT was newly created in an effort to enhance national science and technology initiatives by President Moon Jae-In. Professor Im said at the news conference, “I would like to make a sustainable, as well as credible, system ensuring the ingenuity of scientists in Korean labs. To this end, I will make every effort to enhance Korea’s innovative research environment in a way to maximize research achievements.”
Discovery of an Optimal Drug Combination: Overcoming Resistance to Targeted Drugs for Liver Cancer
A KAIST research team presented a novel method for improving medication treatment for liver cancer using Systems Biology, combining research from information technology and the life sciences. Professor Kwang-Hyun Cho in the Department of Bio and Brain Engineering at KAIST conducted the research in collaboration with Professor Jung-Hwan Yoon in the Department of Internal Medicine at Seoul National University Hospital. This research was published in Hepatology in September 2017 (available online from August 24, 2017). Liver cancer is the fifth and seventh most common cancer found in men and women throughout the world, which places it second in the cause of cancer deaths. In particular, Korea has 28.4 deaths from liver cancer per 100,000 persons, the highest death rate among OECD countries and twice that of Japan. Each year in Korea, 16,000 people get liver cancer on average, yet the five-year survival rate stands below 12%. According to the National Cancer Information Center, lung cancer (17,399) took the highest portion of cancer-related deaths, followed by liver cancer (11,311) based on last year data. Liver cancer is known to carry the highest social cost in comparison to other cancers and it causes the highest fatality in earlier age groups (40s-50s). In that sense, it is necessary to develop a new treatment that mitigates side effects yet elevates the survival rate. There are ways in which liver cancer can be cured, such as surgery, embolization, and medication treatments; however, the options become limited for curing progressive cancer, a stage in which surgical methods cannot be executed. Among anticancer medications, Sorafenib, a drug known for enhancing the survival rate of cancer patients, is a unique drug allowed for use as a targeted anticancer medication for progressive liver cancer patients. Its sales reached more than ten billion KRW annually in Korea, but its efficacy works on only about 20% of the treated patients. Also, acquired resistance to Sorafenib is emerging. Additionally, the action mechanism and resistance mechanism of Sorafenib is only vaguely identified.Although Sorafenib only extends the survival rate of terminal cancer patients less than three months on average, it is widely being used because drugs developed by global pharmaceutical companies failed to outperform its effectiveness. Professor Cho’s research team analyzed the expression changes of genes in cell lines in response to Sorafenib in order to identify the effect and the resistance mechanism of Sorafenib. As a result, the team discovered the resistance mechanism of Sorafenib using Systems Biology analysis. By combining computer simulations and biological experiments, it was revealed that protein disulfide isomerase (PDI) plays a crucial role in the resistance mechanism of Sorafenib and that its efficacy can be improved significantly by blocking PDI. The research team used mice in the experiment and discovered the synergic effect of PDI inhibition with Sorafenib for reducing liver cancer cells, known as hepatocellular carcinoma. Also, more PDIs are shown in tissue from patients who possess a resistance to Sorafenib. From these findings, the team could identify the possibility of its clinical applications. The team also confirmed these findings from clinical data through a retrospective cohort study. “Molecules that play an important role in cell lines are mostly put under complex regulation. For this reason, the existing biological research has a fundamental limitations for discovering its underlying principles,” Professor Cho said. “This research is a representative case of overcoming this limitation of traditional life science research by using a Systems Biology approach, combining IT and life science. It suggests the possibility of developing a new method that overcomes drug resistance with a network analysis of the targeted drug action mechanism of cancer.” The research was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT. (Figure 1. Simulation results from cellular experiments using hepatocellular carcinoma) (Figure 2. Network analysis and computer simulation by using the endoplasmic reticulum (ER) stress network) (Figure 3. ER stress network model)
Global ITTP Graduates 12 Public Officials from 11 Countries
The 18th Global Information and Telecommunication Technology Program (ITTP) graduated 12 public officials from 11 countries in a commencement ceremony held on August 23. Distinguished guests, faculty, and family of graduates including President Sung-Chul Shin, the Chair of the School of Business and Technology Youngsun Kown, and the Director of Global ITTP Jaejung Rho attended the commencement. Ghana Ambassador Joseph Agoe, Mrs. Lyudmila Fen, the spouse of Uzbekistan Ambassador Vitali Fen, and other dignitaries came to congratulate the 12 master’s students on their successful graduation. The Global ITTP was launched in 2006 and offers customized master’s and doctoral degree programs to elite public officials from diverse countries on information and communication technology. This program plays a vital role for transferring Korea’s advanced ICT to countries whose industries are in the budding stages. Since 2006, the program has produced 181 alumni (48 PhDs and 133 masters) from 60 countries. In his congratulatory message during the ceremony, President Shin congratulated the graduates on the long journey they had been through while completing their courses and welcomed the newest addition of KAIST 12 alumni. “Back in the 1960s, Korea was one of the poorest countries in the world. Korea’s GDP stood at less than 100 US dollars. Through it all, Korean companies are now taking the lead in the global high-tech market, emerging as movers and shakers. I believe that ‘VIP’ changed it all; in other words, visionary leaders, innovative ideas, and passionate people all combined to make the difference in Korea,” said President Shin. He also shared a new formula for success in the wake of the new industrial environment of the Fourth Industrial Revolution with the graduates who will soon begin a new ambitious professional journey in their countries. “I think Innovation, Collaboration, and Speed will be the key words to make a difference in every sector of each and every country in this dynamic new era. When making a national development strategies, please keep in mind ‘ICS’ for the development of your country as well as the world’s sustainable development.” Finally, he said, “As a KAIST alumnus, always be sincere wherever you work and whatever you do during your service. I advise you to become a leader who is doing one’s best at all times.” ☞ Link to the 18th commencement address
Cooperative Tumor Cell Membrane-Targeted Phototherapy
A KAIST research team led by Professor Ji-Ho Park in the Bio and Brain Engineering Department at KAIST developed a technology for the effective treatment of cancer by delivering synthetic receptors throughout tumor tissue. The study, led by Ph.D. candidate Heegon Kim, was published online in Nature Communications on June 19. Cancer targeted therapy generally refers to therapy targeting specific molecules that are involved in the growth and generation of cancer. The targeted delivery of therapeutics using targeting agents such as antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumors have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. To solve this problem, the team constructed a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumor cell membrane-selective localization of synthetic receptors to amplify the subsequent targeting of therapeutics. Here, synthetic and biological nanocomponents refer to liposomes and extracellular vesicles, respectively. The synthetic receptors are first delivered selectively to tumor cell membranes in the perivascular region using liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the synthetic receptors are transferred to neighboring cells and further spread throughout the tumor tissues where the molecular targets are limited. Hitchhiking extracellular vesicles for delivery of synthetic receptors was possible since extracellular vesicles, such as exosomes, mediate intercellular communications by transferring various biological components such as lipids, cytosolic proteins, and RNA through a membrane fusion process. They also play a supportive role in promoting tumor progression in that tumor-derived extracellular vesicles deliver oncogenic signals to normal host cells. The team showed that this tumor cell membrane-targeted delivery of synthetic receptors led to a uniform distribution of synthetic receptors throughout a tumor and subsequently led to enhanced phototherapeutic efficacy of the targeted photosensitizer. Professor Park said, “The cooperative tumor targeting system is expected to be applied in treating various diseases that are hard to target.” The research was funded by the Basic Science Research Program through the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, and the National R&D Program for Cancer Control funded by the Ministry for Health and Welfare. (Ph.D. candidates Hee Gon Kim (left) and Chanhee Oh) Figure 1. A schematic of a cooperative tumor targeting system via delivery of synthetic receptors. Figure 2. A confocal microscopic image of a tumor section after cooperative targeting by synthetic receptor delivery. Green and magenta represent vessels and therapeutic agents inside a tumor respectively.
KAIST Professors Sweep the Best Science and Technology Award
(Distinguished Professors Sang Yup Lee (left) and Kyu-Young Whang) Distinguished Professors Sang Yup Lee from the Department of Chemical and Biomolecular Engineering and Kyu-Young Whang of the College of Computing were selected as the winners of the "2017 Korea Best Science and Technology Award" by the Ministry of Science, ICT and Future Planning (MSIP) and the Korea Federation of Science and Technology Societies. The award, which was established in 2003, is the highest honor bestowed to the two most outstanding scientists in Korea annually. This is the first time that KAIST faculty members have swept the award since its founding. Distinguished Professor Lee is renowned for his pioneering studies of system metabolic engineering, which produces useful chemicals by utilizing microorganisms. Professor Lee has developed a number of globally-recognized original technologies such as gasoline production using micro-organisms, a bio-butanol production process, microbes for producing nylon and plastic raw materials, and making native-like spider silk produced in metabolically engineering bacterium which is stronger than steel but finer than human hair. System metabolism engineering was also selected as one of the top 10 promising technologies in the world in 2016 by the World Economic Forum. Selected as one of the world’s top 20 applied bioscientists in 2014 by Nature Biotechnology, he has many ‘first’ titles in his academic and research careers. He was the first Asian to win the James Bailey Award (2016) and Marvin Johnson Award (2012), the first Korean elected to both the US National Academy of Science (NAS) and the National Academy of Engineering (NAE) this year. He is the dean of KAIST institutes, a multi and interdisciplinary research institute at KAIST. He serves as co-chair of the Global Council on Biotechnology and as a member of the Global Future Council on the Fourth Industrial Revolution at the World Economic Forum. Distinguished Professor Whang, the first recipient in the field of computer science in this award, has been recognized for his lifetime achievement and contributions to the development of the software industry and the spreading of information culture. He has taken a pioneering role in presenting novel theories and innovative technologies in the field of database systems such as probabilistic aggregation, multidimensional indexing, query, and database and information retrieval. The Odysseus database management system Professor Hwang developed has been applied in many diverse fields of industry, while promoting the domestic software industry and its technical independence. Professor Hwang is a fellow at the American Computer Society (ACM) and life fellow at IEEE. Professor Whang received the ACM SIGMOD Contributions Award in 2014 for his work promoting database research worldwide, the PAKDD Distinguished Contributions Award in 2014, and the DASFAA Outstanding Contributions Award in 2011 for his contributions to database and data mining research in the Asia-Pacific region. He is also the recipient of the prestigious Korea (presidential) Engineering Award in 2012.
2017 World Friends ICT KAIST Sets Off to Ethiopia, Tanzania
KAIST launched the ‘2017 World Friends ICT KAIST’ on 21 June at a ceremony held at the Faculty Club. The event was attended by 40 student volunteers and faculty members including President Sung-Chul Shin and student volunteers. The ‘2017 World Friends ICT KAIST’ is an oversees volunteer program aimed at providing ICT education for students from developing countries and for cultural exchange. The program was organized by the KAIST Leadership Center and sponsored by the National Information Agency (NIA) since 2015. President Sung-Chul Shin delivered words of encouragement to start the opening ceremony, followed by an oath-taking by the volunteer group, safety training, and a commemorative photoshoot. This year’s World Friends ICT volunteer group consisted of 32 students and 2 staff members to lead and to support the team. The group was divided into eight teams including APP-frica, KAI-Tigers, and WITH (4 members per team) to volunteer in Addis Ababa Institute of Technology (AAIT) and Adama Science and Technology University in Ethiopia (ASTU), as well as Nelson Mandela African Institute of Science and Technology (NM-AIST) in Tanzania. The teams will educate local students on ICT and promote cultural exchanges. The volunteer period is from July 7 to August 5, lasting about a month. KAIST conducted primary document examinations and interviews from April 27 to May 18 on volunteer candidates who registered to take part, and selected 32 student volunteers. A total of 68 students registered to volunteer, resulting in a 1:2.1 competition rate. The volunteering program was customized to the local needs of Ethiopia and Tanzania and thus consisted of ICT education, cultural exchanges, volunteering at farms on the weekends, and science experiments. The area with the most focus by the volunteer team is ICT education, which accounts for 70% of the total volunteer activities. The aim is to educate Ethiopian students at AAIT and ASTU on Windows, MS Office, Adobe Photoshop, and using smartphones. In Tanzania, the team is to volunteer with students of NM-AIST to provide ICT application education such as water tank control using appropriate technology and Arduino to local high school students. The team is also planning to promote cultural exchanges by preparing K-Pop dancing, traditional Korean games such as Korean shuttlecock game (jegichagi) and Korean wrestling (ssireum), traditional cooking such as bibimbab and half-moon-shaped rice cake (songpyeon), and teaching the Korean language, as well as preparing cultural performances with local university students. On the weekends, the team will visit local farms to volunteer, and local elementary schools and orphanages to conduct science experiments for children, as well as physical education and art activities. (Photo caption: Volunteers poses with faculty and staff members including President Sung-Chul Shin at a ceremony on June 21.)
Bio-based p-Xylene Oxidation into Terephthalic Acid by Engineered E.coli
KAIST researchers have established an efficient biocatalytic system to produce terephthalic acid (TPA) from p-xylene (pX). It will allow this industrially important bulk chemical to be made available in a more environmentally-friendly manner. The research team developed metabolically engineered Escherichia coli (E.coli) to biologically transform pX into TPA, a chemical necessary in the manufacturing of polyethylene terephthalate (PET). This biocatalysis system represents a greener and more efficient alternative to the traditional chemical methods for TPA production. This research, headed by Distinguished Professor Sang Yup Lee, was published in Nature Communications on May 31. The research team utilized a metabolic engineering and synthetic biology approach to develop a recombinant microorganism that can oxidize pX into TPA using microbial fermentation. TPA is a globally important chemical commodity for manufacturing PET. It can be applied to manufacture plastic bottles, clothing fibers, films, and many other products. Currently, TPA is produced from pX oxidation through an industrially well-known chemical process (with a typical TPA yield of over 95 mol%), which shows, however, such drawbacks as intensive energy requirements at high temperatures and pressure, usage of heavy metal catalysts, and the unavoidable byproduct formation of 4-carboxybenzaldehyde. The research team designed and constructed a synthetic metabolic pathway by incorporating the upper xylene degradation pathway of Pseudomonas putida F1 and the lower p-toluene sulfonate pathway of Comamonas testosteroni T-2, which successfully produced TPA from pX in small-scale cultures, with the formation of p-toluate (pTA) as the major byproduct. The team further optimized the pathway gene expression levels by using a synthetic biology toolkit, which gave the final engineered E. coli strain showing increased TPA production and the complete elimination of the byproduct. Using this best-performing strain, the team designed an elegant two-phase (aqueous/organic) fermentation system for TPA production on a larger scale, where pX was supplied in the organic phase. Through a number of optimization steps, the team ultimately achieved production of 13.3 g TPA from 8.8 g pX, which represented an extraordinary yield of 97 mol%. The team has developed a microbial biotechnology application which is reportedly the first successful example of the bio-based production of TPA from pX by the microbial fermentation of engineered E. coli. This bio-based TPA technology presents several advantages such as ambient reaction temperature and pressure, no use of heavy metals or other toxic chemicals, the removable of byproduct formation, and it is 100% environmentally compatible. Professor Lee said, “We presented promising biotechnology for producing large amounts of the commodity chemical TPA, which is used for PET manufacturing, through metabolically engineered gut bacterium. Our research is meaningful in that it demonstrates the feasibility of the biotechnological production of bulk chemicals, and if reproducible when up-scaled, it will represent a breakthrough in hydrocarbon bioconversions.” Ph.D. candidate Zi Wei Luo is the first author of this research (DOI:10.1038/ncomms15689).The research was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) of the Ministry of Science, ICT & Future Planning through the National Research Foundation of Korea. Figure: Biotransformation of pX into TPA by engineered E. coli. This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced TPA from pX. The engineered E. coli was developed through reconstituting a synthetic metabolic pathway for pX conversion to TPA and optimized for increased TPA yield and byproduct elimination. Two-phase partitioning fermentation system was developed for demonstrating the feasibility of large-scale production of TPA from pX using the engineered E. coli strains, where pX was supplied in the organic phase and TPA was produced in the aqueous phase.
Observation of the Phase Transition of Liquid Crystal Defects
KAIST researchers observed the phase transition of topological defects formed by liquid crystal (LC) materials for the first time. The phase transition of topological defects, which was also the theme of the Nobel Prize for Physics in 2016, can be difficult to understand for a layperson but it needs to be studied to understand the mysteries of the universe or the underlying physics of skyrmions, which have intrinsic topological defects. If the galaxy is taken as an example in the universe, it is difficult to observe the topological defects because the system is too large to observe some changes over a limited period of time. In the case of defect structures formed by LC molecules, they are not only a suitable size to observe with an optical microscope, but also the time period in which the phase transition of a defect occurring can be directly observed over a few seconds, which can be extended to a few minutes. The defect structures formed by LC material have radial, circular, or spiral shapes centering on a singularity (defect core), like the singularity that was already introduced in the famous movie "Interstellar,” which is the center point of black hole. In general, LC materials are mainly used in liquid crystal displays (LCDs) and optical sensors because it is easy to control their specific orientation and they have fast response characteristics and huge anisotropic optical properties. It is advantageous in terms of the performance of LCDs that the defects of the LC materials are minimized. The research team led by Professor Dong Ki Yoon in the Graduate School of Nanoscience and Technology did not simply minimize such defects but actively tried to use the LC defects as building blocks to make micro- and nanostructures for the patterning applications. During these efforts, they found the way to directly study the phase transition of topological defects under in-situ conditions. Considering the LC material from the viewpoint of a device like a LCD, robustness is important. Therefore, the LC material is injected through the capillary phenomenon between a rigid two-glass plate and the orientation of the LCs can be followed by the surface anchoring condition of the glass substrate. However, in this conventional case, it is difficult to observe the phase transition of the LC defect due to this strong surface anchoring force induced by the solid substrate. In order to solve this problem, the research team designed a platform, in which the movement of the LC molecules was not restricted, by forming a thin film of LC material on water, which is like oil floating on water. For this, a droplet of LC material was dripped onto water and spread to form a thin film. The topological defects formed under this circumstance could show the thermal phase transition when the temperature was changed. In addition, this approach can trace back the morphology of the original defect structure from the sequential changes during the temperature changes, which can give hints to the study of the formation of topological defects in the cosmos or skyrmions. Prof. Yoon said, “The study of LC crystal defects itself has been extensively studied by physicists and mathematicians for about 100 years. However, this is the first time that we have observed the phase transition of LC defects directly.” He also added, "Korea is leading in the LCD industry, but our basic research on LCs is not at the world's research level." The first author of this study is Dr. Min-Jun Gimand supported by a grant from the National Research Foundation (NRF) and funded by the Korean Government (MSIP). The research result was published on May 30, 2017 in Nature Communications. Figure 1. The phase transition of the LC topological defect on cooling. Figure 2. Polarizing optical microscopy images of topological defects depending on the strength of the director field. (a,b,e) Convergent director field arrangements of LC molecules and corresponding schematic images; (c,d,f) Divergent director field arrangements of LC molecules and corresponding schematic images.
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