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KAIST Researchers Receive Awards at the 13th Asian Congress on Biotechnology
(From left: Seon Young Park, Dr. So Young Choi, and Yoojin Choi) Researchers in the laboratory of KAIST Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering swept awards at the 13th Asian Congress on Biotechnology held in Thailand last month. The conference awarded a total of eight prizes in the areas of best research and best poster presentation. This is an exceptional case in which members of one research team received almost half of the awards at an international conference. Dr. So Young Choi received the Best Research Award, while Ph.D. candidates Yoojin Choi and Seon Young Park each received the Best Poster Presentation Award at the conference held in Khon Kaen, Thailand from July 23 to 27. The Asian Congress on Biotechnology is an international conference in which scientists and industry experts in Asia and from around the world gather to present recent research findings in the field of biotechnology. At the conference, around 400 researchers in biotechnology from 25 countries, including Korea, gathered to present and discuss various research findings under the theme of “Bioinnovation and Bioeconomy.” Distinguished Professor Sang Yup Lee attended the conference to give the opening plenary lecture on the topic of ‘Systems Strategies in Biotechnology.’ Professor Lee announced, “I have attended international conferences with students for the last 20 years, but this is the first in which my team received three awards at an international conference that only honors a total of eight awards, three for Best Research and five for Best Presentation.” Dr. Choi presented research results on poly (lactate-co-glycolate) (PLGA) synthesis through a biological method using micro-organisms and received the Best Research Award. PLGA is a random copolymer of DL-lactic and glycolic acids and is a biopolymer widely used for biomedical applications. PLGA is biodegradable, biocompatible, and nontoxic, and thus has been approved by the US Food and Drug Administration (FDA) for its use in implants, drug delivery, and sutures. Dr. Choi’s research was deemed to be innovative for synthesizing PLGA from glucose and xylose in cells through metabolic engineering of E.Coli. Dr. Choi received her Ph.D. under the supervision of Distinguished Professor Lee this February and is currently conducting post-doc research. Ph.D. candidate Choi presented her research on the use of recombinant E.Coli for the biological synthesis of various nanoparticles and received the Best Poster Presentation award. Choi used recombinant E.Coli-expressing proteins and peptides that adsorb to heavy metals to biologically synthesize diverse metal nanoparticles such as single-nanoparticle including gold and silver, quantum dots, and magnetic nanoparticles for the first time. The synthesized nanoparticles can be used in the fields of bio-imaging, diagnosis, environment, and energy. Ph.D. candidate Park, who also received the Best Poster Presentation award, synthesized and increased production of astanxanthin, a strong antioxidant found in nature, in E.Coli using metabolic engineering. Astanxanthin is a carotenoid pigment found in salmon and shrimp that widely used in health products and cosmetics.
2017.08.01
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KAIST to Host the 2017 AI World Cup in November
KAIST, the birthplace of the Robot World Cup in 1996, now presents a new technology matchup, the AI World Cup this November, which will be held at KAIST. The event is being organized by the Machine Intelligence and Robotics Multi-Sponsored Research and Education Platform (MIR-MSREP) of KAIST. The online, simulated AI soccer game, based on rolling updates, will be a draw for avid online gamers and tech-savvy university students from around the nation. The tournament is comprised of three events: ▲A 5 on 5 AI soccer match to be played after self-learning using AI technology in an online simulation environment ▲Commentary in which online soccer videos are analyzed and commented on, and ▲Game reporters who will write articles on online soccer event results. The participants will undergo a month-long online practice period in October and compete in preliminary matches from November 1 through 24. The top teams that scored the highest accumulated points will compete in the finals on December 1. In the finals, each team’s AI technology implementation method will be evaluated to select the final winning team. To ensure a successful event, KAIST will host a briefing session for participants on July 28. Technological prowess and early exposure to AI accumulated at KAIST led to the launching of this tournament. Professor Jong-Hwan Kim, the chair of the Organizing Committee of the AI World Cup, hosted the first ever Robot World Cup back in 1996. His concept has now evolved into the emerging technology of AI and the members of the Organizing Committee encompass the professors from the various departments of electrical engineering, computing, industrial and systems engineering, aerospace engineering, civil and environmental engineering, and the graduate schools of Green Transportation, Cultural Technology, and Science and Technology Policy. In particular, ongoing convergence research initiatives incorporating AI into a wide arrays of disciplines such as bio, nano, and IT, played a crucial role for making this AI World Cup happen. Professor Kim said, “The winner of this year’s competition will be awarded a certificate and a small gift. In 2018, we aim to expand the event to an international scale by allowing international teams.” Any undergraduate or graduate student in Korea can apply to participate in the ‘AI World Cup 2017’. KAIST will host a public trial event during the ‘Open KAIST’ event period to be held November 2-3 to help participating students understand the event better. ‘Open KAIST’ allows the general public to personally visit and experience what goes on in engineering departments and laboratories on the KAIST main campus. It is hosted by the College of Engineering every two years and is the largest event hosted by KAIST. To participate in the ‘AI World Cup 2017,’ teams consisting of Korean undergraduates or graduate students can fill out application forms and submit them by September 30 on http://mir.kaist.ac.kr .
2017.07.14
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Structural Insights into the Modulation of Synaptic Adhesion by MDGA for Synaptogenesis
Synapses connected by various synaptic adhesion molecules are communication spaces between neurons for transmitting information. Among various synaptic adhesion molecules, neuroligins are arguably the most widely studied class of postsynaptic adhesion molecules, which mainly interact with presynaptic neurexins to induce excitatory or inhibitory synapse development. Recently, the membrane-associated mucin (MAM) domain-containing GPI anchor protein 1 (MDGA1) has been characterized as a key suppressor of Neuroligin-2/Neurexin-1β-mediated inhibitory synapse development, but how it acts remains a mystery. In a recent issue of Neuron, published on June 21, 2017, a research team led by Professor Ho Min Kim at the Graduate School of Medical Science and Engineering of KAIST reported the three-dimensional structure of MDGA1/Neuroligin-2 complex and mechanistic insights into how MDGAs negatively modulate synapse development governed by Neurexins/Neuroligins trans -synaptic adhesion complex. MDGA1 consists of six Ig-like domains, fibronectin type III repeat domain, and MAM domain . The crystal structure of MDGA1/Neuroligin-2 complex reveals that they form the 2:2 hetero-tetrameric complex and only the Ig1-Ig2 domains of MDGA1 are involved in interactions with Neuroligin-2. The structural comparison between the MDGA1/Neuroligin-2 and Neurexin-1β/Neuroligin-1 complexes intriguingly indicates that the Neuroligin-2 region binding to MDGA1 largely overlaps with that of Neurexin-1β, but the interaction interface of the MDGA1/Neuroligin-2 complex is much larger than that of the Neurexin-1β/Neuroligin-1 complex. This explains why Neuroligin-2 binds stronger to MDGA1 than Neurexin-1β, and how the favored MDGA1 binding to Neuroligin-2 sterically blocks the interaction between Neuroligin-2 and Neurexin-1β, which is critical for the suppression of inhibitory synapse development. “Although we found that MDGA Ig domains (Ig 1 and Ig 2) are sufficient to form a complex with NL2, other extracellular domains, including Ig 3–6, FN III, and MAM domains, may also contribute to stable cis-interactions between MDGA1 and Neuroligin-2 by providing conformational flexibility. Therefore, further structural analysis of full-length MDGA will be required,” Professor Kim said. Neuroligin-2 specifically promotes the development of inhibitory synapses, whereas neuroligin-1 promotes the development of excitatory synapses. Recently, not only MDGA1, but also MDGA2 have emerged as synaptic regulators for the development of excitatory or inhibitory synapses. In vitro biochemical analysis in this research clearly demonstrates that Neuroligin-1 and Neuroligin-2 bind to both MDGA1 and MDGA2 with comparable affinity. However, pull-down assays using detergent-solubilized mouse brain membrane fractions show the specific interaction of MDGA1 with Neuroligin-2, but not with Neuroligin-1. “This suggests that unidentified processes may dictate the selective association of MDGA1 with Neuroligin-2 in vivo , ” explained Professor Jaewon Ko at the Daegu Gyeongbuk Institute of Science and Technology (DGIST). A balance between excitatory and inhibitory synapses is crucial to healthy cognition and behavior. Mutations in neuroligins, neurexins, and MDGAs, which can disrupt the excitatory/inhibitory balance, are associated with neuropsychiatric diseases such as autism and schizophrenia. Jung A Kim at KAIST, first author in this study, said, “Our discovery from integrative investigations are an important first step both for a better understanding of Neuroligin/Neurexin synaptic adhesion pathways and MDGA-mediated regulation of synapse development as well as the development of potential new therapies for autism, schizophrenia, and epilepsy.”
2017.07.10
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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.
2017.07.07
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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.
2017.07.03
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Professor Poong Hyun Seong Selected as Fellow of the ANS
Professor Poong Hyun Seong of the Department of Nuclear and Quantum Engineering was selected as a fellow of the American Nuclear Society. The selection was announced at their annual meeting held in San Francisco on June 12, in recognition of Professor Seong's contributions to the field of nuclear instrumentation, control andhuman factors engineering. Founded in 1954, the American Nuclear Society selects scholars who have made outstanding achievements and contributions to the development of the nuclear engineering field each year. Professor Seong's researches in the field of nuclear instrumentation, control and human factors engineering have contributed to the safe operation of nuclear power plants, to the development of systems to maintain nuclear power plants safely in the event of emergency and to the enhancement of effective response capabilities of nuclear power plant operators. His researches significantly contributed to the safety improvement of nuclear power plants and have been recognized worldwide. Professor Seong said, "Korea has emerged as a nuclear powerhouse. I think not only my academic career but our national reputation in the field of nuclear research has been well recognized by our global peers.” Professor Seong has served as president of the Korean Nuclear Society, editor in chief of Nuclear Engineering and Technology, and as a commissioner of the Korean Nuclear Safety Commission. He is currently working as a commissioner of the Korean Atomic Energy Commission.
2017.06.29
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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.)
2017.06.29
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Top 10 Emerging Technologies of 2017
The World Economic Forum’s Expert Network and Global Future Councils in collaboration with Scientific American and its Board of Advisors announced the top 10 emerging technologies of 2017 on June 26 in Dalian, China where the 2017 Summer Davos Forum is being held. Each technology was chosen for its potential to improve lives, transform industries, and safeguard the planet. The KAIST delegation, headed by President Sung-Chul Shin, is participating in the forum’s diverse activities including IdeasLab and GULF (Global University Leaders Forum). KAIST is the only Korean representative participating in the IdeasLab. KAIST Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, director of KAIST Institute, has served as a committee member of the Global Agenda Council on Emerging Technologies since 2012 and Global Future Council on the Fourth Industrial Revolution. He also chairs the Global Future Council on Biotechnologies. Professor Lee said, “Very diverse technological breakthroughs were proposed for the final list of candidates. We made the final selections through very in-depth discussion with experts in each field. We focused on the technologies which have a level of maturity that will enable them to be adopted widely within three to five years." The top 10 emerging technologies are (courtesy from https:// www.weforum.org/agenda/2017/06/these-are-the-top-10-emerging-technologies-of-2017): 2017 10대 기술. 1. Liquid biopsies Liquid biopsies mark a step forward in the fight against cancer. First, they are an alternative where traditional tissue-based biopsies are not possible. Second, they provide a full spectrum of information compared to tissue samples, which only reflect the information available in the sample. Lastly, by homing in on circulating-tumor DNA (ctDNA), genetic material that routinely finds its way from cancer cells into the bloodstream, disease progression or resistance to treatment can be spotted much faster than otherwise relying on symptoms or imaging. 2. Harvesting clean water from air The ability to extract clean water from air is not new, however existing techniques require high moisture levels and a lot of electricity. This is changing. A team from MIT and University of California, Berkeley has successfully tested a process using porous crystals that convert the water using no energy at all. 3. Deep learning for visual tasks Computers are beginning to recognize images better than humans. Thanks to deep learning, an emerging field of artificial intelligence, computer-vision technologies are increasingly being used in applications as diverse as driving autonomous vehicles, medical diagnostics, damage assessment for insurance claims, and monitoring water levels and crop yield. 4. Liquid fuels from sunshine Can we mimic the humble leaf to create artificial photosynthesis to generate and store energy? The prospects are looking increasingly positive. The answer lies in using sunlight-activated catalysts to split water molecules into water and hydrogen, and then using the same hydrogen to convert CO2 into hydrocarbons. 5. The Human Cell Atlas An international collaboration aimed at deciphering the human body, called the Human Cell Atlas, was launched in October 2016. The project aims to identify every cell type in every tissue; learn exactly which genes, proteins, and other molecules are active in each type, and the processes which control that activity. 6. Precision farming The Fourth Industrial Revolution is providing farmers with a new set of tools to boost crop yield and quality while reducing water and chemical use. Sensors, robots, GPS, mapping tools, and data-analytics software are all being used to customize the care that plants need. 7. Affordable catalysts for green vehicles Progress is being made on a promising zero-emission technology, the hydrogen-fed fuel cell. Progress to date has been stymied by the high price of catalysts which contain platinum. However, much progress has been made in reducing reliance on this rare and expensive metal, and the latest developments involve catalysts that include no platinum, or in some cases no metal at all. 8. Genomic vaccines Vaccines based on genes are superior to more conventional ones in a number of ways. They are faster to manufacture, which is crucial during violent outbreaks. Compared to manufacturing proteins in cell cultures or eggs, producing genetic material should also be simpler and less expensive. 9. Sustainable design of communities Applying green construction to multiple buildings at once has the potential to revolutionize the amount of energy and water we consume. Sending locally-generated solar power to a smart microgrid could reduce electricity consumption by half and reduce carbon emissions to zero if a project currently under development at the University of California at Berkeley goes according to plan. 10. Quantum computing Quantum computers’ almost limitless potential has only ever been matched by the difficulty and cost of their construction. This explains why today the small ones that have been built have not yet managed to exceed the power of supercomputers. But progress is being made and in 2016 the technology firm IBM provided public access to the first quantum computer in the cloud.
2017.06.28
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KAIST to Participate in the Summer Davos Forum
KAIST will participate in the 2017 Summer Davos Forum in Dalian, China from June 27 to 29. The Summer Davos Forum with the official title “Annual Meeting of New Champions” is an annual international meeting co-hosted by China and the World Economic Forum (WEF) to address global issues which has been held since 2007. Focusing on this year’s theme ‘Achieving Inclusive Growth in the Fourth Industrial Revolution,’ science and technology experts from 90 different countries will participate in various sessions to present on and discuss pending global innovative issues. KAIST is to be the only Korean university to run ‘IdeasLab,’ in which researchers will introduce current research trends and discuss ideas with global leaders. This is the sixth year for KAIST to run IdeasLab. This year’s IdeasLab has the theme ‘Materials of the Future,’ and will include presentations and discussions on materials developed at KAIST which could lead the Fourth Industrial Revolution. President Sung-Chul Shin, the chairman of the session, will first introduce the current status of KAIST and IdeasLab, followed by a presentation of cutting-edge integrated research findings by KAIST professors. President Shin will also participate in various sessions organized by the Global University Leaders Forum (GULF) as discussion leader. President Shin is the only Korean member of GULF, a community comprised of the presidents of the world’s top 27 universities. Other members include the presidents of the University of Oxford and the University of Cambridge in the U.K., MIT, Harvard, Stanford, and Columbia Universities in the US, and the University of Tokyo in Japan. Further, President Shin will participate in a strategy session for inclusive growth in the era of the Fourth Industrial Revolution and a meeting with the WEF directors. The Dean of KAIST Institutes, Distinguished Professor Sang Yup Lee from the Chemical and Biomolecular Engineering Department, who has been invited to the Davos Forum and Summer Davos Forum for the last 15 years, is to present in the ‘Future of Life: Medicine’ session to introduce advancements in traditional medicine through systems biology such as his research on microbiomes (gut microbes). Professor Lee, as the chair of the Global Future Council on Biotechnology at the WEF, and committee member of the Annual Meeting of the Global Future Councils on the Fourth Industrial Revolution, is to participate in various bio-sessions and the Fourth Industrial Revolution banquet session to lead the discussions. President Shin said, “KAIST has been sharing global research findings with global leaders through IdeasLab at the Davos Forum for the past six years and it has always been well received.” He continued, “The forum will be the place for in-depth discussion on the technological changes that accompany the Fourth Industrial Revolution and human-centered development plan, as well as introducing innovative research and integrated research findings from KAIST.” This year’s speakers include Li Keqiang, the current Premier of the State Council of China; Guo Ping, the rotating C.E.O. of Huawei; and Ya-Qin Zhang, the President of Baidu, a company leading technological innovation in various fields such as robotics and autonomous vehicles. Two thousand distinguished guests in politics, administration, finance, and academia from 90 countries are to participate in the meeting.
2017.06.21
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KATT Tops at Appropriate Technology Competition
The KAIST Appropriate Technology Team (KATT) consisting of KAIST international students received gold and bronze awards at ‘the 9th Creative Design Competition for the Other 90%’. This year’s competition was hosted by the Ministry of Science, ICT and Future Planning at Seoul National University’s Global Convention Plaza on May 26. Undergraduate and graduate students nationwide formed 65 teams to participate in the competition. The aim of the competition is to discover appropriate technology and sustainable design items to enhance quality of life for those with no or little access to science technology and its products around the world. This year’s competition categorized the designs into IT; water and energy; agriculture, hygiene, safety, and housing; and education. The teams were evaluated on their presentations and prototypes. KATT produced alarm warning bracelets for people in developing countries and smart hybrid dryers for agricultural products. The alarm warning bracelets were designed for those living in tsunami risk zones; they use wireless communication technology to receive and transmit warning signals and can be produced for less than $4. The smart hybrid dryers featured solar energy generation, aimed to help those with low income in subtropical, low-altitude regions with unstable climates, since there are currently no drying methods for agricultural products without direct exposure to sunlight. Therefore, the hybrid dryers allowed drying regardless of the weather, and thus increased the storage and distribution efficiency of agricultural products. Ashar Alam from India who participated in developing the alarm warning bracelet said, “Through the appropriate technology club, I recognized problems in India that also affect neighboring countries such as Indonesia and Bangladesh. I wanted to actively use the science and technology knowledge I have accumulated in KAIST for the less fortunate.” He continued, “It was meaningful to develop the product using the respective talents of students from various countries with the spirit of developing appropriate technology.” (Photo caption: Alarm warning bracelet team received the gold award)
2017.06.12
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Mutations Unveiled that Predispose Lung Cancer Cells to Refractory Histologic Transformation
Cancer pedigree analysis reveals the mutations in RB1 and TP53 genes play a key role in treatment-resistant, cancer cell-type transformation during EGFR inhibitor therapy for lung cancers. Research led by Korean medical scientists has discovered that a specific type of drug resistance mechanism to EGFR inhibitor therapy in lung cancer is predisposed by mutations in two canonical cancer-related genes: RB1 and TP53. Published in Journal of Clinical Oncology on May 12, the study also found those mutations can be detectable in patients' tumors at the point of clinical diagnosis. Therefore, it can be used as strong markers in clinic for predicting poor outcome for the targeted treatment for lung adenocarcinoma. Lung adenocarcinoma is the most common type of lung cancer, and about 15% of patients in Western countries and 50% of patients in Asian countries have mutations in the EGFR gene, which is critical for the development of lung cancer. Patients with lung adenocarcinoma harboring the EGFR mutation show favorable responses to EGFR inhibitors such as erlotinib (Tarceva) or gefitinib (Iressa), but ultimately relapse with drug-resistant tumors. Since the initial report in 2006, it has been known that in about 5~15% of patients, the lung adenocarcinoma cells undergo a mysterious transformation into a very different cancer cell type called “small cell lung cancer,” a much more aggressive lung cancer subtype, common in cigarette smokers. To find out the genetic basis of this process, the researchers compared the genome sequences of multiple cancer tissues acquired during the treatment courses of patients whose tumors underwent small-cell transformation. They reconstructed the cancer cell pedigree by comparing mutations between cancer tissues, and identified that RB1 and TP53 genes are completely inactivated by mutations already in their lung adenocarcinoma tissues. "We tried to compare the somatic mutational profile of pre-EGFR inhibitor treatment lung adenocarcinomas and post-treatment small cell carcinomas and to reconstruct the pedigrees of the cancer evolution in each patient. Strikingly, both copies of RB1 and TP53 genes were already inactivated at the stage of lung adenocarcinomas in all sequenced cases," said Dr. Jake June-Koo Lee, the first author from KAIST. They further pursued the clinical implications of RB1 and TP53 inactivation by investigating 75 EGFR-mutated lung adenocarcinoma tissues from patients who received EGFR inhibitor therapy, including patients with small-cell transformation. In this analysis, the lung adenocarcinomas with a complete inactivation of both RB1 and TP53 genes tended to have a 43-times greater risk of transformation into small cell lung cancer during their EGFR inhibitor treatment courses. Dr. Young Seok Ju, the co-last author from KAIST, explained, "This study shows the power of entire genome analyses to better understand the mechanisms underlying mysterious phenomenon encountered in clinic. Upon accurate bioinformatics, we are finding cancer-specific somatic mutations from the whole-genomes of patients’ cancer cells. These mutations allow us to track the evolution of cancer cells throughout the extraordinary clinical course of a special set of lung cancers." The complete inactivation of both RB1 and TP53 tumor suppressor genes is found in a minor (<10%) subset of lung adenocarcinoma. This study suggests that the clinical course against targeted therapy is endogenously different for the cancers in the subgroup, and specific drug-resistance mechanisms are predisposed by the two genetic mutations. Indeed, RB1 and TP53 double inactivation is a genetic hallmark of primary small cell lung cancer, observed in nearly all cases. "We are actively investigating patient tumor tissues to develop optimal surveillance plans and treatment options for patients with lung adenocarcinomas more prone to small-cell transformation," said Dr. Tae Min Kim, the co-last author from Seoul National University Hospital. The researchers are implementing their findings into lung cancer clinics by screening the RB1 and TP53 mutational status in lung adenocarcinoma patients receiving EGFR inhibitor treatment, and following their treatment courses to develop a treatment strategy for those patients. This research (doi.org/10.1200/JCO.2016.71.9096) was funded by the National Research Foundation of Korea (NRF-2013H1A2A1032691 to J.-K.L., NRF-2014R1A2A2A05003665 to Y.T.K.); Korea Institute of Science and Technology Information (K-16-L03-C02-S02 to J.L.); and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, which was funded by the Ministry of Health and Welfare (HI14C1234 to T.M.K., HI16C2387 to Y.S.J.) Figure. Phylogeny analysis of serially-acquired tumors A. Phylogeny trees of sequenced cases (LC1−LC4) are reconstructed from the WGS data. Conceptual illustrations are depicted with grey color. Circles indicate major clones of the tumors. The length of each branch is proportional to the number of mutations that occurred in the branch. Mutations of cancer-related genes in each branch are indicated with arrows. The time points of relevant treatments are summarized below the trees. B. Mutations of RB1 and TP53 in two early LADCs (LC1b and LC4a) are visualized using Integrative Genomics Viewer (left panel). Allele-specific copy number analysis shows loss of heterozygosity of chromosomes 13 and 17 in both early LADCs and EGFR TKI-resistant SCLCs (right panel). C. Clonal evolution of LC1 is described with clinical history and tumor volumes. The horizontal axis represents the time from the diagnosis (0), and the vertical axis indicates the volume of tumors calculated from the computed tomography images. Abbreviations: LADC, lung adenocarcinoma; SCLC, small cell lung cancer
2017.06.07
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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.
2017.06.05
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