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Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.) A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources. Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18. There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways. The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway. In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption. The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose. Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.” This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18
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Center for Industrial Future Strategy Takes Off at KAIST
(Professor Wonjoon Kim from the School of Business and Technology Management) Professors from KAIST and major international universities launched a mega-scale research center focusing on the Fourth Industrial Revolution, named the Center for Industrial Future Strategy (CIFS). This center is funded by the National Research Foundation Korea and will receive 2.25 billion KRW over four years. Directed by Professor Wonjoon Kim from the School of Business and Technology Management, the center is comprised of ten top-tier researchers and four research associates, including Professor Hawoon Jeong (KAIST), Professor Scott Stern (MIT), Professor Aaron Chatterji (Duke University), Dr. Yong Suk Lee (Stanford University) and Professor Hyejin Youn (Northwestern University). The center will conduct research on technical, social, and economic changes derived by a new paradigm of technological innovation. Moreover, they will study policies and strategies in relation to innovation in the corporate and government sectors to achieve economic growth in a sustainable manner. The center will also propose policies and strategies in a variety of economic and industrial settings to establish a sustainable and global innovation ecosystem. To carry out these studies successfully, CIFS will further expand the AIEA-NBER Conference with the Asia Innovation and Entrepreneurship Association (AIEA) and the National Bureau of Economic Research (NBER) in which numerous Nobel Laureates in Economics are affiliated. They will also comprise thematic research teams with co-founding universities to build stronger cooperation with one another. Besides the academic cooperation, the center will also build partnerships with international organizations, including the Asian Development Bank and the Inter-American Development Bank to carry out their missions at multilateral levels. Their research topics include changes to value chains in a new paradigm of technological innovation, labor market changes in the Fourth Industrial Revolution, sharing economies and social interests, big data, artificial intelligence & privacy policy, and innovation & ethical and institutional countermeasures to AI technology. Professor Kim said, “The new paradigm of technological innovation is evolving social, economic, and industrial structures, such as R&D, industry, technology, labor, finance, and institutions. The Center will contribute to proposing policies and strategies so that Korea, as well as the international community, can take appropriate measures to these big changes.”
2018.09.11
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Electron Heating in Weakly Ionized Collisional Plasmas
(from left: Professor Wonho Choe and Research Professor Sanghoo Park) A KAIST research team successfully identified the underlying principles behind electron heating, which is one of the most important phenomena in plasmas. As the electric heating determines wide range of physical and chemical properties of plasmas, this outcome will allow relevant industries to extend and effectively customize a range of plasma characteristics for their specific needs. Plasma, frequently called the fourth state of matter, can be mostly formed by artificially energizing gases in standard temperature (25°C) and pressure (1 atm) range. Among the many types of plasma, atmospheric-pressure plasmas have been gaining a great deal of attention due to their unique features and applicability in various scientific and industrial fields. Because plasma characteristics strongly depends on gas pressure in the sub-atmospheric to atmospheric pressure range, characterizing the plasma at different pressures is a prerequisite for understanding the fundamental principles of plasmas and for their industrial applications. In that sense, information on the spatio-temporal evolution in the electron density and temperature is very important because various physical and chemical reactions within a plasma arise from electrons. Hence, electron heating has been an interesting topic in the field of plasma. Because collisions between free electrons and neutral gases are frequent under atmospheric-pressure conditions, there are physical limits to measuring the electron density and temperature in plasmas using conventional diagnostic tools, thus the principles behind free electron heating could not be experimentally revealed. Moreover, lacking information on a key parameter of electron heating and its controlling methods is troublesome and limit improving the reactivity and applicability of such plasmas. To address these issues, Professor Wonho Choe and his team from the Department of Nuclear and Quantum Engineering employed neutral bremsstrahlung-based electron diagnostics in order to accurately examine the electron density and temperature in target plasmas. In addition, a novel imaging diagnostics for two dimensional distribution of electron information was developed. Using the diagnostic technique they developed, the team measured the nanosecond-resolved electron temperature in weakly ionized collisional plasmas, and they succeeded in revealing the spatiotemporal distribution and the fundamental principle involved in the electron heating process. The team successfully revealed the fundamental principle of the electron heating process under atmospheric to sub-atmospheric pressure (0.25-1atm) conditions through conducting the experiment on the spatiotemporal evolution of electron temperature. Their findings of the underlying research data on free electrons in weakly ionized collisional plasmas will contribute to enhancing the field of plasma science and their commercial applications. Professor Choe said, “The results of this study provide a clear picture of electron heating in weakly ionized plasmas under conditions where collisions between free electrons and neutral particles are frequent. We hope this study will be informative and helpful in utilizing and commercializing atmospheric-pressure plasma sources in the near future.” Articles related to this research, led by Research Professor Sanghoo Park, were published in Scientific Reports on May 14 and July 5. Figure 1. Nanosecond-resolved visualization of the electron heating structure. Spatiotemporal evolution of 514.5-nm continuum radiation,Te, Ar I emission Figure 2. Nanosecond-resolved visualization of electron heating. Spatiotemporal evolution of neutral bremsstrahlung at 514.5 nm
2018.09.10
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There Won't Be a Singularity: Professor Jerry Kaplan
(Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST) “People are so concerned about super intelligence, but the singularity will not happen,” said Professor Jerry Kaplan at Stanford University, an AI guru and Silicon Valley entrepreneur during a lecture at KAIST. He visited KAIST to give a lecture on Artificial Intelligence: Think Again on September 6. Professor Kaplan said that some people argue that Korea’s AI research is behind the US and China but he doesn’t agree with that. “Korea is the most digitally connected one and has the world’s best engineers in the field. Korean companies are building products the consumers really like at reasonable prices. Those are attracting global consumers,” he added. Instead of investing loads of money on AI research, he suggested three tasks for Korea taking a better position in the field of AI: Collecting and saving lots of data; training engineers, not the research talents in AI; and investing in AI infrastructure and relieving regulations by the government. Referring to AI hype, Professor Kaplan argued that machines are intelligent, but they do not think in the way humans can, and assured the audience that the singularity some futurists predict will not be coming. He said, “Machine learning is a tool extracting useful information, but it does not mean they are so smart that they are taking over the world.” (Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST) But what has made us believing AI myths? He first began pointing out how AI has been mythicized by three major drivers. Those are the entertainment industry, the popular media, and the AI community all wanting to attract more public attention and prestige. The abovementioned drivers are falsely making robots more human and are adding human characteristics. Instead of being captivated by those AI myths and thinking about how to save the world from robots, he strongly argued, “We need to develop standards for the unintended side effects from AI.” To provide machines socially and ethically mingling with the human world, he believed principles should be set as follows: Define the Safe Operating Envelope (SOE), “safe modes” when out of bounds, study human behavior programmatically, certification and licensing standards, limitations on machine “agency,” and basic computational ethics such as when it is okay to break the law. Professor Kaplan gave a positive view of AI for humans. “The future will be bright, thanks to AI. They do difficult work and help us and that will drive wealth and quality of life. The rich might get richer, but the benefits will spread throughout the people. It is time to think of innovative ways for using AI for building better world,” he concluded.
2018.09.10
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NEREC Summer Program Keeps Fellows Thinking, Engaged in Nuclear Nonproliferation
Nuclear technology is more than just technology. It is the fruit of the most advanced science and technology. It also requires high standards of policymaking and global cooperation for benefiting the technology. As part of the fifth annual Nuclear Nonproliferation Education and Research Center (NEREC) Summer Fellows Program at KAIST, 24 students from 15 countries participated in six-week intensive education and training program. NEREC is the only university-based center dedicated to nuclear nonproliferation education and research established in 2014. The program, which provides multidisciplinary lectures and seminars on nuclear technology and policy as well as international relations, was designed to nurture global nuclear technology experts well equipped in three areas: in-depth knowledge of technology, applicability gained from sound policy building, and negotiating for international cooperation. It now has grown into the most popular summer program at KAIST. During the program from July 6 to August 18, participants were able to engage in enriching and stimulating learning experiences in tandem with policies and technology for the utilization and provision of peaceful and safe nuclear technology. Participating fellows also had to conduct a group research project on a given topic. This year, they explored nuclear nonproliferation issues in relation to nuclear exports and brainstormed some recommendations for current policy. They presented their outcomes at the 2018 NEREC Conference on Nuclear Nonproliferation. After intensive lecture sessions and group research work, the fellows went off to key policy think-tanks, nuclear research institutes, and research power facilities in Korea, Japan, and China. “NEREC emphasizes nuclear nonproliferation issues related to civilian nuclear power and the associated nuclear fuel cycle development from the point of technology users. I am very glad that the number of participants are increasing year by year,” said the Director of NEREC Man-Sung Yim, a professor in the Department of Nuclear and Quantum Engineering. Participants’ majors vary from nuclear engineering to international relations to economics. The fellows divided into two groups of graduate and undergraduate courses. They expressed their deep satisfactory in the multidisciplinary lectures by scholars from KAIST, Seoul National University, and Korea National Defense University. Many participants reported that they learned a lot, not only about policy and international relations but on the research they are conducting and what the key issues will be in dealing for producing meaningful research work. Moad Aldbissi from the KTH Royal Institute of Technology is one of the students who shared the same view. He said, “Coming from a technical background in nuclear engineering, I managed to learn a lot about nuclear policy and international relations. The importance of integrating the technical and political fields became even clearer.” Most students concurred that they recognized how important it was to make international collaboration in this powerful field for each country through this program. “As an engineering student, I just approached this program like an empty glass in policy areas. While working with colleagues during the program, I came to understand how important it is to make cooperation in these fields for the better result of national development and international relations,” said Thanataon Pornphatdetaudom from the Tokyo Institute of Technology. To Director Yim, this program is becoming well positioned to educate nuclear policy experts in a number of countries of strategic importance. He believes the continuous supply of these experts will contribute to promoting global nuclear nonproliferation and the peaceful use of nuclear energy while the use of nuclear technology continues.
2018.09.04
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Adding Smart to Science Museum
KAIST and the National Science Museum (NSM) created an Exhibition Research Center for Smart Science to launch exhibitions that integrate emerging technologies in the Fourth Industrial Revolution, including augmented reality (AR), virtual reality (VR), Internet of Things (IoTs), and artificial intelligence (AI). There has been a great demand for a novel technology for better, user-oriented exhibition services. The NSM continuously faces the problem of not having enough professional guides. Additionally, there have been constant complaints about its current mobile application for exhibitions not being very effective. To tackle these problems, the new center was founded, involving 11 institutes and universities. Sponsored by the National Research Foundation, it will oversee 15 projects in three areas: exhibition-based technology, exhibition operational technology, and exhibition content. The group first aims to provide a location-based exhibition guide system service, which allows it to incorporate various technological services, such as AR/VR to visitors. An indoor locating system named KAILOS, which was developed by KAIST, will be applied to this service. They will also launch a mobile application service that provides audio-based exhibition guides. To further cater to visitors’ needs, the group plans to apply a user-centered ecosystem, a living lab concept to create pleasant environment for visitors. “Every year, hundred thousands of young people visit the National Science Museum. I believe that the exhibition guide system has to be innovative, using cutting-edge IT technology in order to help them cherish their dreams and inspirations through science,” Jeong Heoi Bae, President of Exhibition and Research Bureau of NSM, emphasized. Professor Dong Soo Han from the School of Computing, who took the position of research head of the group, said, “We will systematically develop exhibition technology and contents for the science museum to create a platform for smart science museums. It will be the first time to provide an exhibition guide system that integrates AR/VR with an indoor location system.” The center will first apply the new system to the NSM and then expand it to 167 science museums and other regional museums.
2018.09.04
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Potential Drug to Cure Ciliopathies
(from left: Professor Joon Kim and PhD candidate Yong Joon Kim) Ciliopathies are rare disorders involving functional and structural abnormalities of cilia. Although they are rare, they may reach 1 in 1,000 births. Unfortunately, there are no small-molecule drugs for treating ciliary defects. A KAIST research team conducted successful research that introduces a potential treatment that will be a foundation for developing drugs to treat the disease as well as a platform for developing small-molecule drugs for similar genetic disorders. It was found that mutations in genes required for the formation or function of primary cilia cause ciliopathies and they result in cerebellar disorders, kidney dysfunction, and retinal degeneration. Primary cilia are cell organelles playing a crucial role in the human body. They participate in intercellular signal transduction during embryonic development and allow retinal photoreceptor cells to function. Currently, there are no approved drugs available for treating most ciliopathies. In fact, this is the case for most of the rare genetic disorders involving functional abnormalities through genetic mutation, and gene therapy is usually the only treatment available. To tackle this issue, a team led by Professor Joon Kim from the Graduate School of Medical Science and Engineering and Ho Jeong Kwon from Yonsei University constructed a cell that mimics a gene-mutated CEP290, one of the main causes of ciliopathies, through genome editing. They then used cell-based compound library screening to obtain a natural small-molecule compound capable of relieving defects in ciliogenesis, the production of cilia. The CEP290 protein forms a complex with a ciliopathy protein called NPHP5 to support the function of the ciliary transition zone. In cases where the CEP290 protein is not formed due to a genetic mutation, NPHP5 will not function normally. Here, the compound was confirmed to partially restore the function of the complex by normalizing the function of NPHP5. The team also identified that the compound is capable of retarding retinal degeneration by injecting the compound into animal models. As a result, they discovered a lead compound for developing medication to treat ciliopathy patients involving retinal degeneration. Hence, the findings imply that chemical compounds that target other proteins interacting with the disease protein can mitigate shortages of a disease protein in recessive genetic disorders. PhD candidate Yong Joon Kim stated, “This study shows how genetic disorders caused by genetic mutation can be treated with small-molecule drugs.” Professor Kim said, “Since the efficacy of the candidate drug has been verified through animal testing, a follow-up study will also be conducted to demonstrate the effect on humans.” This research was published in the Journal of Clinical Investigation on July 23. Figure 1. Identification of compounds that rescue ciliogenesis defects caused by CEP290 knockout Figure 2. Eupatilin injection ameliorates M-opsin trafficking and electrophysiological response of cone photoreceptors in rd16 mice
2018.08.30
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The MSE/CBE Int'l Workshop Explores Big Ideas in Emerging Materials
(KAIST President Sung-Chul Shin with scholars participated in the workshop) The MSE/CBE International Workshop brought together editors from key academic journals in multidisciplinary materials science and scholars from leading universities at KAIST on Aug. 7. The workshop hosted ten distinguished speakers in the fields of nanostructures for next-generation emerging applications, chemical and bio-engineering, and materials innovation for functional applications. They explored opportunities and challenges for reinventing novel materials that will solve complex problems. (From left: Professor Buriak, Professor Swager and Professor Il-Doo Kim) Speakers included: Chief Editor of Nature Materials Vincent Dusastre; Editor-in- Chief of ACS NANO and professor at UCLA Paul S. Weiss; Jillian M. Buriak, Editor-in-Chief of Chemistry of Materials; Associate Editor of Macromolecules and professor at MIT Timothy M. Swager; Coordinating Editor of Acta Materialia and Head of the Department of Materials Science and Engineering at MIT Christopher A. Schuh; Editor-in-Chief of Biotechnology Journal and Metabolic Engineering and Distinguished Professor at KAIST Sang-Yup Lee; Associate Editor of Energy Storage Materials and professor at KAIST Sang Ouk Kim; Professor Jeffrey C. Grossman at MIT; Professor Zhenan Bao at Stanford University; and Professor Hyuck Mo Lee, head of the Department of Materials Science and Engineering at KAIST. Interdisciplinary materials research holds the key to building technological competitiveness in many industrial sectors extending from energy, environment, and health care to medicine and beyond. It has also been the bedrock of KAIST’s scholarship and research innovation. More than 200 faculty members in the field of materials science produce about 800 SCI papers every year. The two departments of materials science and chemical biomolecular engineering are leading KAIST’s global reputation, as they were both ranked 13th and 14th in the QS World University Ranking by Subject this year. (Professor Il-Doo Kim fromt he Department of Materials Science Engineering) Professor Il-Doo Kim from the Department of Materials Science Engineering has been the chair of this workshop from 2016. In hosting the second one this year, he said that he hopes this year’s workshop will inspire many materials scientists to have big ideas and work to make those big ideas get noticed in order to have a real impact. (KAIST President Sung-Chul Shin) President Sung-Chul Shin, who is a physicist specializing in materials physics, expressed his keen interest in the workshop, saying innovative materials made of unthinkable and noble combinations will be the key factor in determining the competitiveness of new technology and new industries. He lauded international collaborations for making new materials and the scholarly passion to evaluate the materials’ characteristics that made this significant progress possible. Dr. Vincent Dusastre, chief editor of Nature Materials, presented recent trends in materials for energy. He described how the rational design and improvement of materials’ properties can lead to energy alternatives which will compete with existing technologies. He pointed out that given the dramatic fundamental and practical breakthroughs that are taking place in the realization of solar cells with high energy-conversion efficiency, the improvement of batteries for electric vehicles and the grid is also a major challenge. He stressed, “Key advances in sustainable approaches beyond Li-ion batteries and control of redox processes are also greatly needed.” Meanwhile, ACS NANO Editor-in-Chief Paul S. Weiss spoke on the importance of heterogeneity in the structure and function of molecules and nanoscale assemblies. He stressed that such extensiveness of multi-interdisciplinary research will accelerate a greater impact as indicated when the fields of neuroscience and microbiome converged with nanoscience and nanotechnology. Editor-in-Chief of Chemistry of Materials Professor Jillian M. Buriak from the University of Alberta described how predictive models and machine learning can replace time consuming empirical device production and screening. By understanding and pinpointing the frustrating bottlenecks in the design of stable and efficient organic photovoltaics, much faster throughput can be obtained to enable a more direct pathway to stability, efficiency, and finally commercialization.
2018.08.13
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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
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Mechanism Leading to Cortical Malformation from Brain-Only Mutations Identified
Focal malformations of cortical development (FMCDs) are a heterogeneous group of brain cortical abnormalities. These conditions are the most common causes of medically refractory epilepsy in children and are highly associated with intellectual disability, developmental delay, and autism-spectrum disorders. Despite a broad spectrum of cortical abnormalities in FMCDs, the defective migration of neuronal cells is considered a key pathological hallmark. A research team led by Professor Jeong Ho Lee in the Graduate School of Medical Science and Engineering at KAIST has recently investigated the molecular mechanism of defective neuronal migration in FMCDs. Their research results were published online in Neuron on June 21, 2018. The research team previously demonstrated that brain-only mutations in the mechanistic target of rapamycin (MTOR) gene causes focal cortical dysplasia, one major form of FMCDs leading to intractable epilepsy in children. However, the molecular mechanisms by which brain-only mutations in MTOR lead to cortical dyslamination and defective neuronal migration in FMCDs remain unclear. To study the molecular mechanism of brain cortical dyslamination, the research team utilized patients’ brain tissues and modeled the MTOR mutation-carrying cell and animal models recapitulating the pathogenesis and symptoms of FMCD patients. By performing comprehensive molecular genetic experiments, they found that the formation of primary cilia, one of cellular organelles, was disrupted in MTOR mutation-carrying neurons and demonstrated that this ciliary disruption was a cause of cortical dyslamination in FMCDs. MTOR mutations prevented degradation of the OFD1 protein, one of the negative regulators of ciliary formation. As a result, the OFD1 protein was abnormally accumulated in MTOR mutation-carrying neurons, causing focal cortical dyslamination. By suppressing the expression of the OFD1 protein, the research team was able to rescue the defective formation of primary cilia, leading to the restoration of cortical dyslamination and defective neuronal migration considerably. Based on these results, the research team is carrying out further research to develop novel therapeutics for patients with FMCDs caused by brain-only mutations. This work was supported by grants from the Suh Kyungbae Foundation and Citizens United for Research in Epilepsy. The research paper is titled “Brain Somatic Mutations in MTOR Disrupt Neuronal Ciliogenesis, Leading to Focal Cortical Dyslamination.” (Digital Object Identifier #: 10.1016/j.neuron.2018.05.039) Picture 1: The disrupted formation of primary cilia in brain tissues of FMCD mouse models and patients with FMCDs caused by brain somatic mutations in MTOR. Picture 2: The rescue of defective ciliary formation in FMCD mouse models leading to the restoration of cortical dyslamination and defective neuronal migration.
2018.07.02
View 7982
Taming AI: Engineering, Ethics, and Policy
(Professor Lee, Professor Koene, Professor Walsh, and Professor Ema (from left)) Can AI-powered robotics could be adequate companions for humans? Will the good faith of users and developers work for helping AI-powered robots become the new tribe of the digital future? AI’s efficiency is creating new socio-economic opportunities in the global market. Despite the opportunities, challenges still remain. It is said that efficiency-enforcing algorithms through deep learning will take an eventual toll on human dignity and safety, bringing out the disastrous fiascos featured in the Terminator movies. A research group at the Korean Flagship AI Project for Emotional Digital Companionship at KAIST Institute for AI (KI4AI) and the Fourth Industrial Intelligence Center at KAIST Institute co-hosted a seminar, “Taming AI: Engineering, Ethics, and Policy” last week to discuss ways to better employ AI technologies in ways that upholds human values. The KI4AI has been conducting this flagship project from the end of 2016 with the support of the Ministry of Science and ICT. The seminar brought together three speakers from Australia, Japan, and the UK to better fathom the implications of the new technology emergence from the ethical perspectives of engineering and discuss policymaking for the responsible usage of technology. Professor Toby Walsh, an anti-autonomous weapon activist from New South Wales University in Australia continued to argue the possible risk that AI poses to malfunction. He said that an independent ethics committee or group usually monitors academic institutions’ research activities in order to avoid any possible mishaps. However, he said there is no independent group or committee monitoring the nature of corporations’ engagement of such technologies, while its possible threats against humanity are alleged to be growing. He mentioned that Google’s and Amazon’s information collecting also pose a potent threat. He said that ethical standards similar to academic research integrity should be established to avoid the possible restricting of the dignity of humans and mass destruction. He hoped that KAIST and Google would play a leading role in establishing an international norm toward this compelling issue. Professor Arisa Ema from the University of Tokyo provided very compelling arguments for thinking about the duplicity of technology and how technology should serve the public interest without any bias against gender, race, and social stratum. She pointed out the information dominated by several Western corporations like Google. She said that such algorithms for deep learning of data provided by several Western corporations will create very biased information, only applicable to limited races and classes. Meanwhile, Professor Ansgar Koene from the University of Nottingham presented the IEEE’s global initiative on the ethics of autonomous and intelligence systems. He shared the cases of industry standards and ethically-aligned designs made by the IEEE Standards Association. He said more than 250 global cross-disciplinary thought leaders from around the world joined to develop ethical guidelines called Ethically Aligned Design (EAD) V2. EAD V2 includes methodologies to guide ethical research and design, embedding values into autonomous intelligence systems among others. For the next step beyond EAD V2, the association is now working for IEEE P70xx Standards Projects, detailing more technical approaches. Professor Soo Young Lee at KAIST argued that the eventual goal of complete AI is to have human-like emotions, calling it a new paradigm for the relationship between humans and AI-robots. According to Professor Lee, AI-powered robots will serve as a good companion for humans. “Especially in aging societies affecting the globe, this will be a very viable and practical option,” he said. He pointed out, “Kids learn from parents’ morality and social behavior. Users should have AI-robots learn morality as well. Their relationships should be based on good faith and trust, no longer that of master and slave. He said that liability issues for any mishap will need to be discussed further, but basically each user and developer should have their own responsibility when dealing with these issues.
2018.06.26
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Distinguished Professor Koh Donates His Ho-Am Prize Money
(From left: Distinguished Professor Gou Young Koh and KAIST President Sung-Chul Shin) Distinguished Professor Gou Young Koh from the Graduate School of Medical Science and Engineering donated one hundred million KRW to KAIST that he received for winning the Ho-Am Prize. Professor Koh, who is widely renowned for angiogenesis, was appointed as the 2018 laureate of the 28th Ho-Am Prize for demonstrating the effective reduction of tumor progression and metastasis via tumor vessel normalization. He made the donation to the Graduate School of Medical Science and Engineering, where he conducted his research. “As a basic medical scientist, it is my great honor to receive this prize for the recognition of my research outcome. I will give impetus to research for continuous development,” Professor Koh said. Professor Koh also received the 5th Asan Award in Medicine in 2012 and the 7th Kyung-Ahm Award in 2011. He was also the awardee of the 17th Wunsch Medical Award. He has donated cash prizes to the school every time he is awarded. KAIST President Sung-Chul Shin said, “I would like to express my gratitude to the professor for his generous donation to the school. It will be a great help fostering outstanding medical scientists. Professor Koh received his MD-PhD from the Medical School of Chonbuk National University. After finishing his post-doctoral program at Cornell University and Indiana State University, he was appointed as a professor at Chonbuk National University and POSTECH. Currently, he holds the position of distinguished professor at KAIST and director of the IBS Center for Vascular Research.
2018.06.20
View 5070
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