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Mathematical Modeling Makes a Breakthrough for a New CRSD Medication
PhD Candidate Dae Wook Kim (Left) and Professor Jae Kyoung Kim (Right) - Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy - Mathematicians’ new modeling has identified major sources of interspecies and inter-individual variations in the clinical efficacy of a clock-modulating drug: photosensitivity and PER2 level. This enabled precision medicine for circadian disruption. A KAIST mathematics research team led by Professor Jae Kyoung Kim, in collaboration with Pfizer, applied a combination of mathematical modeling and simulation tools for circadian rhythms sleep disorders (CRSDs) to analyze the animal data generated by Pfizer. This study was reported in Molecular Systems Biology as the cover article on July 8. Pharmaceutical companies have conducted extensive studies on animals to determine the candidacy of this new medication. However, the results of animal testing do not always translate to the same effects in human trials. Furthermore, even between humans, efficacy differs across individuals depending on an individual’s genetic and environmental factors, which require different treatment strategies. To overcome these obstacles, KAIST mathematicians and their collaborators developed adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions. A circadian rhythm is a 24-hour cycle in the physiological processes of living creatures, including humans. A biological clock in the hypothalamic suprachiasmatic nucleus in the human brain sets the time for various human behaviors such as sleep. A disruption of the endogenous timekeeping system caused by changes in one’s life pattern leads to advanced or delayed sleep-wake cycle phase and a desynchronization between sleep-wake rhythms, resulting in CRSDs. To restore the normal timing of sleep, timing of the circadian clock could be adjusted pharmacologically. Pfizer identified PF-670462, which can adjust the timing of circadian clock by inhibiting the core clock kinase of the circadian clock (CK1d/e). However, the efficacy of PF-670462 significantly differs between nocturnal mice and diurnal monkeys, whose sleeping times are opposite. The research team discovered the source of such interspecies variations in drug response by performing thousands of virtual experiments using a mathematical model, which describes biochemical interactions among clock molecules and PF-670462. The result suggests that the effect of PF-670462 is reduced by light exposure in diurnal primates more than in nocturnal mice. This indicates that the strong counteracting effect of light must be considered in order to effectively regulate the circadian clock of diurnal humans using PF-670462. Furthermore, the team also found the source of inter-patients variations in drug efficacy using virtual patients whose circadian clocks were disrupted due to various mutations. The degree of perturbation in the endogenous level of the core clock molecule PER2 affects the efficacy. This explains why the clinical outcomes of clock-modulating drugs are highly variable and certain subtypes are unresponsive to treatment. Furthermore, this points out the limitations of current treatment strategies tailored to only the patient’s sleep and wake time but not to the molecular cause of sleep disorders. PhD candidate Dae Wook Kim, who is the first author, said that this motivates the team to develop an adaptive chronotherapy, which identifies a personalized optimal dosing time of day by tracking the sleep-wake up time of patients via a wearable device and allows for a precision medicine approach for CRSDs. Professor Jae Kyoung Kim said, "As a mathematician, I am excited to help enable the advancement of a new drug candidate, which can improve the lives of so many patients. I hope this result promotes more collaborations in this translational research.” This research was supported by a Pfizer grant to KAIST (G01160179), the Human Frontiers Science Program Organization (RGY0063/2017), and a National Research Foundation (NRF) of Korea Grant (NRF-2016 RICIB 3008468 and NRF-2017-Fostering Core Leaders of the Future Basic Science Program/ Global Ph.D. Fellowship Program). Figure 1. Interspecies and Inter-patients Variations in PF-670462 Efficacy Figure 2. Journal Cover Page Publication: Dae Wook Kim, Cheng Chang, Xian Chen, Angela C Doran, Francois Gaudreault, Travis Wager, George J DeMarco, and Jae Kyoung Kim. 2019. Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy. Molecular Systems Biology. EMBO Press, Heidelberg, Germany, Vol. 15, Issue No. 7, Article, 16 pages. https://doi.org/10.15252/msb.20198838 Profile: Prof. Jae Kyoung Kim, PhD jaekkim@kaist.ac.kr http://mathsci.kaist.ac.kr/~jaekkim Associate Professor Department of Mathematical Sciences Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Dae Wook Kim, PhD Candidate 0308kdo@kaist.ac.kr http://mathsci.kaist.ac.kr/~jaekkim PhD Candidate Department of Mathematical Sciences Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Dr. Cheng Chang, PhD cheng.chang@pfizer.com Associate Director of Clinical Pharmacology Clinical Pharmacology, Global Product Development Pfizer https://www.pfizer.com/ Groton 06340, USA (END)
2019.07.09
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Two Alumni Win the Korea Best Scientist and Technologist Awards
Vice Chairman Ki-Nam Kim (Left) and Distinguished Professor Sukbok Chang (Right) <ⓒ Photo by MSIT and KOFST> Distinguished KAIST Professor Sukbok Chang from the Department of Chemistry and Vice Chairman Ki-Nam Kim of Samsung Electronics were selected as the winners of the “2019 Korea Best Scientist and Technologist Awards” by the Ministry of Science and ICT (MSIT) and the Korean Federation of Science and Technology Societies (KOFST). The awards, which were first handed out in 2003, are the highest honor bestowed to the two most outstanding scientists in Korea every year, and this year’s awardees are of greater significance as they are both KAIST alumni. Professor Chang was recognized for his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. His research group has also been actively involved in the development of highly selective catalytic systems allowing the controlled defunctionalization of bio-derived platform substrates under mild conditions, and opening a new avenue for the utilization of biomass-derived platform chemicals. The results of his study have been introduced worldwide through many prestigious journals including Science, Nature Chemistry, and Nature Catalysis, making him one of the world's top 1% researchers by the number of references made to his papers by his peers over four consecutive years from 2015 to 2018. Vice Chairman Kim, who received his M.E. degree from KAIST’s School of Electrical Engineering in 1983, has been credited with playing a leading role in the development of system semiconductors. The awards were conferred on July 4 at the opening ceremony of the 2019 Korea Science and Technology Annual Meeting. (END)
2019.07.09
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Deep Learning-Powered 'DeepEC' Helps Accurately Understand Enzyme Functions
(Figure: Overall scheme of DeepEC) A deep learning-powered computational framework, ‘DeepEC,’ will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions. A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner. DeepEC takes a protein sequence as an input and accurately predicts EC numbers as an output. Enzymes are proteins that catalyze biochemical reactions and EC numbers consisting of four level numbers (i.e., a.b.c.d) indicate biochemical reactions. Thus, the identification of EC numbers is critical for accurately understanding enzyme functions and metabolism. EC numbers are usually given to a protein sequence encoding an enzyme during a genome annotation procedure. Because of the importance of EC numbers, several EC number prediction tools have been developed, but they have room for further improvement with respect to computation time, precision, coverage, and the total size of the files needed for the EC number prediction. DeepEC uses three convolutional neural networks (CNNs) as a major engine for the prediction of EC numbers, and also implements homology analysis for EC numbers if the three CNNs do not produce reliable EC numbers for a given protein sequence. DeepEC was developed by using a gold standard dataset covering 1,388,606 protein sequences and 4,669 EC numbers. In particular, benchmarking studies of DeepEC and five other representative EC number prediction tools showed that DeepEC made the most precise and fastest predictions for EC numbers. DeepEC also required the smallest disk space for implementation, which makes it an ideal third-party software component. Furthermore, DeepEC was the most sensitive in detecting enzymatic function loss as a result of mutations in domains/binding site residue of protein sequences; in this comparative analysis, all the domains or binding site residue were substituted with L-alanine residue in order to remove the protein function, which is known as the L-alanine scanning method. This study was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 20, 2019, entitled “Deep learning enables high-quality and high-throughput prediction of enzyme commission numbers.” “DeepEC can be used as an independent tool and also as a third-party software component in combination with other computational platforms that examine metabolic reactions. DeepEC is freely available online,” said Professor Kim. Distinguished Professor Lee said, “With DeepEC, it has become possible to process ever-increasing volumes of protein sequence data more efficiently and more accurately.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation of Korea. This work was also funded by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean government, the Ministry of Science and ICT. Profile: -Professor Hyun Uk Kim (ehukim@kaist.ac.kr) https://sites.google.com/view/ehukim Department of Chemical and Biomolecular Engineering -Distinguished Professor Sang Yup Lee (leesy@kaist.ac.kr) Department of Chemical and Biomolecular Engineering http://mbel.kaist.ac.kr
2019.07.09
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KAIST-KU Joint Research Center Opens
The Joint Research Center partnering KAIST and Khalifa University has been completed and the opening of the KAIST center was held on July 5, 2019, following the opening at Khalifa in April. The joint research center will explore the most impactful technologies that will change people’s lives in the face of the new industrial environment brought about by the Fourth Industrial Revolution. The breakthroughs include smart transportation and smart healthcare such as wireless electric vehicles, unmanned vehicles, and wearable healthcare devices. The two institutions signed an MOU on the Joint Research Agreement on the Technology Development for the Fourth Industrial Revolution in 2018. This is the second phase of collaboration following the partnership agreement that was signed in 2010 between the two institutions, which aimed to provide the best science and technology education as well as develop nuclear energy in the UAE. The Khalifa University delegation, headed by Executive Vice President Arif Sultan Al Hammadi and Senior Vice President of Research and Development Steven Griffiths, flew in to attend the ceremony at KAIST. President Sung-Chul Shin, Vice President for Research Hyun Wook Park, Vice President for Planning and Budget Su-chan Chae, Associate Vice President of the International Office Man-Sung Yim joined and Co-Directors of the Joint Research Center Daniel Choi from Khalifa and Jong-Hyun Kim from KAIST also participated in the opening ceremony.
2019.07.06
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Three Professors Receive Han Sung Science Awards
Three KAIST professors swept the 2nd Han Sung Science Awards. Professor Bum-Ki Min from the Departments of Mechanical Engineering and Physics, Professor Sun-Kyu Han from the Department of Chemistry, and Professor Seung-Jae Lee from the Department of Biological Sciences won all three awards presented by the Han Sung Scholarship Foundation, which recognizes promising mid-career scientists in the fields of physics, chemistry, and biological sciences. The awards ceremony will take place on August 16 in Hwaseong. Professor Min was declared as the winner of the physics field in recognition of his outstanding research activities including searching for new application areas for metamaterials and investigating their unexplored functionalities. The metamaterials with a high index of refraction developed by Professor Min’s research team have caught the attention of scientists worldwide, as they can help develop high-resolution imaging systems and ultra-small, hyper-sensitive optical devices. The chemistry field winner, Professor Han, is the youngest awardee so far at 36 years of age. He is often described as one of the most promising next-generation Korean scientists in the field of the total synthesis of complex natural products. Given the fact that this field takes very long-term research, he is making unprecedented research achievements. He is focusing on convergent and flexible synthetic approaches that enable access to not only a single target but various natural products with structural and biosynthetic relevance as well as unnatural products with higher biological potency. Professor Lee was recognized for his contributions to the advancement of biological sciences, especially in aging research. Professor Lee’s team is taking a novel approach by further investigating complex interactions between genetic and environmental factors that affect aging, and identifying genes that mediate the effects. The team has been conducting large-scale gene discovery efforts by employing RNA sequencing analysis, RNAi screening, and chemical mutagenesis screening. They are striving to determine the functional significance of candidate genes obtained from these experiments and mechanistically characterize these genes. (END)
2019.07.03
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Micropatch Made of DNA
Researchers reported the fabrication of microstructure arrays of DNA materials using topographic control. This method provides a platform for forming multiscale hierarchical orientations of soft and biomaterials using a process of simple shearing and controlled evaporation on a patterned substrate. This approach enables the potential of patterning applications using DNA or other anisotropic biomaterials. DNA is one of the most abundant biomaterials found in all living organisms in nature. It has unique characteristics of fine feature size and liquid crystalline phase, enabling to create various kinds of microstructure DNA arrays. Based on these characteristics, DNA has been used as a building block for “origami” and textile art at the nanometer scale. A KAIST research team led by Professors Dong Ki Yoon and Hyungsoo Kim fabricated a DNA-based micropatch using the “coffee ring effect” and its multi-angle control technology, which was published online in Nature Communications on June 7. The research team used cheap DNA material extracted from salmon to realize the micropatch structure with well-aligned knit or ice cream cone shapes. When the DNA material in an aqueous solution is rubbed between two solid substrates while water is evaporating, DNA chains are unidirectionally aligned to make a thin film such as in LCD display devices. The DNA chains can make more complex microstructures such as knit or a texture with ice cream cone shapes when the same procedure is carried out in topographical patterns like microposts (Figure 1). This can be applied to make metamaterials by mixing with functionalized gold nanorods to show plasmonic color. Plasmon resonance is a phenomenon in which electrons vibrate uniformly on the surface of a substrate made of metal, reacting only to light that matches a specific energy to enhance the clarity and expression of colors. For this, the most important factor is the orientation in which the gold nanorods align. That is, when the rods are aligned side by side in one direction, the optical and electrical characteristics are maximized. The research team focused on this point and made the DNA micropatch as a frame to orient the gold nanorods in a unique shape and fabricated a plasmonic color film (Figure 2). Professor Yoon said this study is meaningful in that it deals with the evaporation phenomenon, which has not been studied much in the field of polymers and biopolymers in terms of basic science. He explained, “This will also help maximize the efficiency of polymeric materials that can be orientated in coating, 2D, and 3D printing applications. Furthermore, DNA that exists infinitely in nature can be expected to have industrial application value as a new material since it can easily form complexes with other materials as described in this study.” (Figure 1. The DNA micropatch using topographic control. (a) The experimental scheme. (b) Enlarged image of (e). (c-e) Different micropatches made of DNA using different shearing directions.) (Figure 2. The knit-like structures made of DNA-gold nanorod complex. (a,b) Optical and polarized optical microscopy images. (c-f) Plasmonic colors reflected from aligned DNA-gold nanorod complex depending on the sample rotation.)
2019.07.01
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Professor Lee Elected as a Council Member of ION
< Professor Jiyun Lee > Professor Jiyun Lee from the Department of Aerospace Engineering became the first professor of Korean university to be selected as a council member of the Institute of Navigation (ION), serving specifically as a technical representative. ION is a world-leading organization established in 1945 and dedicated to advancing Positioning, Navigation and Timing (PNT) technologies. ION’s international membership is drawn not only from professionals in the fields of navigation, engineering, astronomy, education, and general aviation and the airline industry, but also from various supporting institutions, corporations, and government agencies. Professor Lee has been actively engaged in the Institute’s academic and community activities as a technical advisor for the Satellite Division in the Asia-Pacific region, a chair of the International Technical Meeting, as well as a section chair of the Global Navigation Satellite System (GNSS+) Conference. She has also published 34 papers in numerous ION journals and conference proceedings over the past 10 years while serving as an associate editor of the ION Navigation Journal. From these activities, Professor Lee was recognized for her academic achievements and committed leadership, which led her to be appointed as the first professor from a Korean university to participate on the Council. She will serve her term over the next two years, and conduct day-to-day operations for the Institute mainly related to developing new programs and strategies for the advancement of PNT technologies and discovering new distinguished members.
2019.06.27
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Anti-drone Technology for Anti-Terrorism Applications
(from top right clockwise: Professor Yongdae Kim, PhD Candidates Yujin Kwon, Juhwan Noh, Hocheol Shin, and Dohyun Kim) KAIST researchers have developed anti-drone technology that can hijack other drones by spoofing its location using fake GPS signals. This technology can safely guide a drone to a desired location without any sudden change in direction in emergency situations, and thus respond effectively to dangerous drones such as those intending to carry out acts of terrorism. Advancements in the drone industry have led to the wider use of drones in our daily lives in areas of reconnaissance, searching and rescuing, disaster prevention and response, and delivery services. At the same time, there has also been a growing concern about privacy, safety, and security issues regarding drones, especially those arising from intrusion into private property and secure facilities. Therefore, the anti-drone industry is rapidly expanding to detect and respond to this possible drone invasion. The current anti-drone systems used in airports and other key locations utilize electronic jamming signals, high-power lasers, or nets to neutralize drones. For example, drones trespassing on airports are often countered with simple jamming signals that can prevent the drones from moving and changing position, but this may result in a prolonged delay in flight departures and arrivals at the airports. Drones used for terrorist attacks – armed with explosives or weapons – must also be neutralized a safe distance from the public and vital infrastructure to minimize any damage. Due to this need for a new anti-drone technology to counter these threats, a KAIST research team led by Professor Yongdae Kim from the School of Electrical Engineering has developed technology that securely thwarts drones by tricking them with fake GPS signals. Fake GPS signals have been used in previous studies to cause confusion inside the drone regarding its location, making the drone drift from its position or path. However, such attack tactics cannot be applied in GPS safety mode. GPS safety mode is an emergency mode that ensures drone safety when the signal is cut or location accuracy is low due to a fake GPS signals. This mode differs between models and manufacturers. Professor Kim’s team analyzed the GPS safety mode of different drone models made from major drone manufacturers such as DJI and Parrot, made classification systems, and designed a drone abduction technique that covers almost all the types of drone GPS safety modes, and is universally applicable to any drone that uses GPS regardless of model or manufacturer. The research team applied their new technique to four different drones and have proven that the drones can be safely hijacked and guided to the direction of intentional abduction within a small margin of error. Professor Kim said, “Conventional consumer drones equipped with GPS safety mode seem to be safe from fake GPS signals, however, most of these drones are able to be detoured since they detect GPS errors in a rudimentary manner.” He continued, “This technology can contribute particularly to reducing damage to airports and the airline industry caused by illegal drone flights.” The research team is planning to commercialize the developed technology by applying it to existing anti-drone solutions through technology transfer.” This research, featured in the ACM Transactions on Privacy and Security (TOPS) on April 9, was supported by the Defense Acquisition Program Administration (DAPA) and the Agency for Defense Development (ADD). Image 1. Experimental environment in which a fake GPS signal was produced from a PC and injected into the drone signal using directional antennae Publication: Juhwan Noh, Yujin Kwon, Yunmok Son, Hocheol Shin, Dohyun Kim, Jaeyeong Choi, and Yongdae Kim. 2019. Tractor Beam: Safe-hijacking of Consumer Drones with Adaptive GPS Spoofing. ACM Transactions on Privacy and Security. New York, NY, USA, Vol. 22, No. 2, Article 12, 26 pages. https://doi.org/10.1145/3309735 Profile: Prof. Yongdae Kim, MS, PhD yongdaek@kaist.ac.kr https://www.syssec.kr/ Professor School of Electrical Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea Profile: Juhwan Noh, PhD Candidate juhwan@kaist.ac.kr PhD Candidate System Security (SysSec) Lab School of Electrical Engineering Korea Advanced Institute of Science and Technology (KAIST) http://kaist.ac.kr Daejeon 34141, Korea (END)
2019.06.25
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Novel Via-Hole-Less Multilevel Metal Interconnection Methods
Forming reliable multi-level metal interconnections is a key technology for integrating devices into organic integrated circuits (ICs). The conventional approach, called “via-hole,” locally removes the insulator and utilizes metal interconnects through the holes. Due to the high sensitivity of organic materials to chemical solvents, heat, and photo-radiation used in conventional “via-hole” methods, alternative printing methods or laser drilling methods have been developed. However, finding a reliable and practical metal interconnection for organic ICs is still challenging. The research team of KAIST Professor Sung Gap Im and Postech Professor Kim Jae-Joon reported a new interconnection method that does not require via-hole formation, “via-hole-less metal interconnection,” in Nature Communications on June 3. Metal electrodes in different layers can be isolated from each other by patterned dielectric layers, where they then can be interconnected to others in the open area where the dielectric layer is not present. See the images below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below. Professor Kim explained, “Our proposed via-hole-less interconnect method using a selectively patterned dielectric overcomes the limitations of the previous time-consuming, one-by-one via-hole formation process and provides reliable methods for creating metal interconnects in organic ICs. We expect the via-hole-less scheme to bring advances to organic IC technology.”
2019.06.18
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Professor Yim Decorated with the Chongjo Order of Merit
Professor Yong-Taek Yim from the Department of Mechanical Engineering was awarded the highest order of merit, the “Chongjo Keunjong Medal,” bestowed to public officials by the government in celebration of Invention Day on May 27. Professor Yim was recognized for his innovative achievements to increase royalty income by introducing an IP-based management system at the Korean Institute of Machinery & Materials. He served as the president of KIMM for three years from 2014. His idea led to new approaches to help explore diverse revenue creating sources such as dividend earnings and share sales, apart from simply relying on technology transfer fees. His efforts to disseminate the in-house R&D results also led to the foundation of six tech-based startups and spinoffs, which generated 11.2 billion KRW in sales. He also helped set up three spinoffs abroad. Professor Yim said, “I pushed employee invention as a new value creator at KIMM. I thank each and every researcher and staff member at KIMM who worked so hard to create such an innovative IP-based R&D environment.”
2019.05.28
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5 Biomarkers for Overcoming Colorectal Cancer Drug Resistance Identified
< Professor Kwang-Hyun Cho's Team > KAIST researchers have identified five biomarkers that will help them address resistance to cancer-targeting therapeutics. This new treatment strategy will bring us one step closer to precision medicine for patients who showed resistance. Colorectal cancer is one of the most common types of cancer worldwide. The number of patients has surpassed 1 million, and its five-year survival rate significantly drops to about 20 percent when metastasized. In Korea, the surge of colorectal cancer has been the highest in the last 10 years due to increasing Westernized dietary patterns and obesity. It is expected that the number and mortality rates of colorectal cancer patients will increase sharply as the nation is rapidly facing an increase in its aging population. Recently, anticancer agents targeting only specific molecules of colon cancer cells have been developed. Unlike conventional anticancer medications, these selectively treat only specific target factors, so they can significantly reduce some of the side-effects of anticancer therapy while enhancing drug efficacy. Cetuximab is the most well-known FDA approved anticancer medication. It is a biomarker that predicts drug reactivity and utilizes the presence of the ‘KRAS’ gene mutation. Cetuximab is prescribed to patients who don’t carry the KRAS gene mutation. However, even in patients without the KRAS gene mutation, the response rate of Cetuximab is only about fifty percent, and there is also resistance to drugs after targeted chemotherapy. Compared with conventional chemotherapy alone, the life expectancy only lasts five months on average. In research featured in the FEBS Journal as the cover paper for the April 7 edition, the KAIST research team led by Professor Kwang-Hyun Cho at the Department of Bio and Brain Engineering presented five additional biomarkers that could increase Cetuximab responsiveness using systems biology approach that combines genomic data analysis, mathematical modeling, and cell experiments. The experimental inhibition of newly discovered biomarkers DUSP4, ETV5, GNB5, NT5E, and PHLDA1 in colorectal cancer cells has been shown to overcome Cetuximab resistance in KRAS-normal genes. The research team confirmed that when suppressing GNB5, one of the new biomarkers, it was shown to overcome resistance to Cetuximab regardless of having a mutation in the KRAS gene. Professor Cho said, “There has not been an example of colorectal cancer treatment involving regulation of the GNB5 gene.” He continued, “Identifying the principle of drug resistance in cancer cells through systems biology and discovering new biomarkers that could be a new molecular target to overcome drug resistance suggest real potential to actualize precision medicine.” This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (2017R1A2A1A17069642 and 2015M3A9A7067220). Image 1. The cover of FEBS Journal for April 2019
2019.05.27
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Engineered Microbial Production of Grape Flavoring
(Image 1: Engineered bacteria that produce grape flavoring.) Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts. Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway. The authors tuned the bacterial metabolic pathway by optimizing the levels of AAMT1, the key enzyme in the process. To maximize production of MANT, the authors tested six strategies, including increasing the supply of a precursor compound and enhancing the availability of a co-substrate. The most productive strategy proved to be a two-phase extractive culture, in which MANT was extracted into a solvent. This strategy produced MANT on the scale of 4.47 to 5.74 grams per liter, a significant amount, considering that engineered microbes produce most natural products at a scale of milligrams or micrograms per liter. According to the authors, the results suggest that MANT and other related molecules produced through industrial processes can be produced at scale by engineered microbes in a manner that would allow them to be marketed as natural one, instead of artificial one. This study, featured at the Proceeding of the National Academy of Sciences of the USA on May 13, was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT. (Image 2. Overview of the strategies applied for the microbial production of grape flavoring.)
2019.05.15
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