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Professor Jin Woo Kim Wins the 14th Macrogen Scientist Award
Professor Jin Woo Kim of the Department of Biological Sciences at KAIST received the 14th Macrogen Scientist Award at the 2017 KSMCB International Conference held in COEX on September 12, 2017. The award is given by the Korean Society for Molecular and Cellular Biology (KSMCB) and sponsored by Macrogen, a service provider of genome research. The award was established in 2004 to recognize biological scientists who have accomplished excellent performance in the field of basic life sciences. Professor Kim has achieved outstanding research performances on nerve development, such as identifying the cause of senile retinal degenerative disease and finding retinal nerve cells that distinguish light and darkness in dark conditions. Recently, he discovered intercellular communication, which controls the development of retinal neurons. His findings have contributed to addressing the principles of maintenance and regeneration of retinal neurons. Since joining KAIST, he has presented approximately 20 papers and published in numerous international journals including Cell Reports, Genes and Development, and EMBO Journal. Moreover, he delivered special lectures at international conferences, universities, and institutes around the world.
2017.09.14
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Professor Dae-Sik Im to Head the Science, Technology and Innovation Office at the Ministry of Science & ICT
(Professor Dae-Sik Im of the Department of Biological Sciences) Professor Dae-Sik Im of the Department of Biological Sciences, a renowned molecular cell biologist, was named to head the Science, Technology and Innovation Office in the Ministry of Science and ICT on August 31. He will be responsible for the oversight of national R&D projects as well as budget deliberation. Joining the KAIST faculty in 2002, he led the Creative Research Center of Cell Division and Differentiation at KAIST. Announcing the nomination of Professor Im, Cheong Wa Dae spokesman Park Soo-Hyun said, “Professor Im will be the best person to lead the innovation of the research infrastructure system for basic research studies. We believe that his expertise and leadership will make a significant impact in enhancing the nation’s science and technology competitiveness. This vice minister position in the Ministry of Science and ICT was newly created in an effort to enhance national science and technology initiatives by President Moon Jae-In. Professor Im said at the news conference, “I would like to make a sustainable, as well as credible, system ensuring the ingenuity of scientists in Korean labs. To this end, I will make every effort to enhance Korea’s innovative research environment in a way to maximize research achievements.”
2017.09.03
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Innovative Nanosensor for Disease Diagnosis
(Figure 1. Sensing Device) (Figure 2. Protein templating route) Breath pattern recognition is a futuristic diagnostic platform. Simple characterizing target gas concentrations of human exhaled breath will lead to diagnose of the disease as well as physical condition. A research group under Prof. Il-Doo Kim in the Department of Materials Science has developed diagnostic sensors using protein-encapsulated nanocatalysts, which can diagnose certain diseases by analyzing human exhaled breath. This technology enables early monitoring of various diseases through pattern recognition of biomarker gases related to diseases in human exhalation. The protein-templated catalyst synthesis route is very simple and versatile for producing not only a single component of catalytic nanoparticles, but also diverse heterogeneous intermetallic catalysts with sizes less than 3 nm. The research team has developed ever more sensitive and selective chemiresistive sensors that can potentially diagnose specific diseases by analyzing exhaled breath gases. The results of this study, which were contributed by Dr. Sang-Joon Kim and Dr. Seon-Jin Choi as first authors were selected as the cover-featured article in the July issue of 'Accounts of Chemical Research,' an international journal of the American Chemical Society. In human breath, diverse components are found including water vapor, hydrogen, acetone, toluene, ammonia, hydrogen sulfide, and carbon monoxide, which are more excessively exhaled from patients. Some of these components are closely related to diseases such as asthma, lung cancer, type 1 diabetes mellitus, and halitosis. Breath analysis for disease diagnosis started from capturing exhaled breaths in a Tedlar bag and subsequently the captured breath gases were injected into a miniaturized sensor system, similar to an alcohol detector. It is possible to analyze exhaled breath very rapidly with a simple analyzing process. The breath analysis can detect trace changes in exhaled breath components, which contribute to early diagnosis of diseases. However, technological advances are needed to accurately analyze gases in the breath, which occur at very low levels, from 1 ppb to 1 ppm. In particular, it has been a critical challenge for chemiresistive type chemical sensors to selectively detect specific biomarkers in thousands of interfering gases including humid vapor. Conventionally, noble metallic catalysts such as platinum and palladium have been functionalized onto metal oxide sensing layers. However, the gas sensitivity was not enough to detect ppb-levels of biomarker species in exhaled breath. To overcome the current limitations, the research team utilized nanoscale protein (apoferritin) in animals as sacrificial templates. The protein templates possess hollow nanocages at the core site and various alloy catalytic nanoparticles can be encapsulated inside the protein nanocages. The protein nanocages are advantageous because a nearly unlimited number of material compositions in the periodic table can be assembled for the synthesis of heterogeneous catalytic nanoparticles. In addition, intermetallic nanocatalysts with a controlled atomic ratio of two different elements can be achieved using the protein nanocages, which is an innovative strategy for finding new types of catalysts. For example, highly efficient platinum-based catalysts can be synthesized, such as platinum-palladium (PtPd), platinum-nickel (PtNi), platinum-ruthenium (PtRu), and platinum-yttrium (PtY). The research team developed outstanding sensing layers consisting of metal oxide nanofibers functionalized by the heterogeneous catalysts with large and highly-porous surface areas, which are especially optimized for selective detection of specific biomarkers. The biomarker sensing performance was improved approximately 3~4-fold as compared to the conventional single component of platinum and palladium catalysts-loaded nanofiber sensors. In particular, 100-fold resistance transitions toward acetone (1 ppm) and hydrogen sulfide (1 ppm) were observed in exhaled breath sensors using the heterogeneous nanocatalysts, which is the best performance ever reported in literature. The research team developed a disease diagnosis platform that recognizes individual breathing patterns by using a multiple sensor array system with diverse sensing layers and heterogeneous catalysts, so that the people can easily identify health abnormalities. Using a 16-sensor array system, physical conditions can be continuously monitored by analyzing concentration changes of biomarkers in exhaled breath gases. Prof. Kim said, “New types of heterogeneous nanocatalysts were synthesized using protein templates with sizes around 2 nm and functionalized on various metal oxide nanofiber sensing layers. The established sensing libraries can detect biomarker species with high sensitivity and selectivity.” He added, “the new and innovative breath gas analysis platform will be very helpful for reducing medical expenditures and continuous monitoring of physical conditions” Patents related to this technology were licensed to two companies in March and June this year.
2017.07.19
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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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Observation of the Phase Transition of Liquid Crystal Defects
KAIST researchers observed the phase transition of topological defects formed by liquid crystal (LC) materials for the first time. The phase transition of topological defects, which was also the theme of the Nobel Prize for Physics in 2016, can be difficult to understand for a layperson but it needs to be studied to understand the mysteries of the universe or the underlying physics of skyrmions, which have intrinsic topological defects. If the galaxy is taken as an example in the universe, it is difficult to observe the topological defects because the system is too large to observe some changes over a limited period of time. In the case of defect structures formed by LC molecules, they are not only a suitable size to observe with an optical microscope, but also the time period in which the phase transition of a defect occurring can be directly observed over a few seconds, which can be extended to a few minutes. The defect structures formed by LC material have radial, circular, or spiral shapes centering on a singularity (defect core), like the singularity that was already introduced in the famous movie "Interstellar,” which is the center point of black hole. In general, LC materials are mainly used in liquid crystal displays (LCDs) and optical sensors because it is easy to control their specific orientation and they have fast response characteristics and huge anisotropic optical properties. It is advantageous in terms of the performance of LCDs that the defects of the LC materials are minimized. The research team led by Professor Dong Ki Yoon in the Graduate School of Nanoscience and Technology did not simply minimize such defects but actively tried to use the LC defects as building blocks to make micro- and nanostructures for the patterning applications. During these efforts, they found the way to directly study the phase transition of topological defects under in-situ conditions. Considering the LC material from the viewpoint of a device like a LCD, robustness is important. Therefore, the LC material is injected through the capillary phenomenon between a rigid two-glass plate and the orientation of the LCs can be followed by the surface anchoring condition of the glass substrate. However, in this conventional case, it is difficult to observe the phase transition of the LC defect due to this strong surface anchoring force induced by the solid substrate. In order to solve this problem, the research team designed a platform, in which the movement of the LC molecules was not restricted, by forming a thin film of LC material on water, which is like oil floating on water. For this, a droplet of LC material was dripped onto water and spread to form a thin film. The topological defects formed under this circumstance could show the thermal phase transition when the temperature was changed. In addition, this approach can trace back the morphology of the original defect structure from the sequential changes during the temperature changes, which can give hints to the study of the formation of topological defects in the cosmos or skyrmions. Prof. Yoon said, “The study of LC crystal defects itself has been extensively studied by physicists and mathematicians for about 100 years. However, this is the first time that we have observed the phase transition of LC defects directly.” He also added, "Korea is leading in the LCD industry, but our basic research on LCs is not at the world's research level." The first author of this study is Dr. Min-Jun Gimand supported by a grant from the National Research Foundation (NRF) and funded by the Korean Government (MSIP). The research result was published on May 30, 2017 in Nature Communications. Figure 1. The phase transition of the LC topological defect on cooling. Figure 2. Polarizing optical microscopy images of topological defects depending on the strength of the director field. (a,b,e) Convergent director field arrangements of LC molecules and corresponding schematic images; (c,d,f) Divergent director field arrangements of LC molecules and corresponding schematic images.
2017.06.02
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Study Identifies the Novel Molecular Signal for Triggering Septic Shock
Professor Seyun Kim’s team at the Department of Biological Sciences reported the mechanism by which cellular signaling transduction networks are precisely controlled in mediating innate immune responses, such as sepsis, by the enzyme IPMK (Inositol polyphosphate multikinase) which is essential for inositol biosynthesis metabolism. In collaboration with Professor Hyun Seong Roh at Seoul National University, the study’s first author, Eunha Kim, a Ph.D. candidate in Department of Biological Sciences, performed a series of cellular, biochemical, and physiological experiments searching for the new function of IPMK enzymes in macrophages. The research findings were published in Science Advances on April 21. Professor Kim’s team has been investigating various inositol metabolites and their biosynthesis metabolism for several years and has multilaterally identified the signaling actions of IPMK for controlling cellular growth and energy homeostasis. This research showed that the specific deletion of IPMK enzymes in macrophages could significantly reduce levels of inflammation and increase survival rates in mice when they were challenged by microbial septic shock and endotoxins. This suggests a role for IPMK enzymes in mediating innate inflammatory responses that are directly related to a host’s defense against pathogenic bacterial infection. The team further discovered that IPMK enzymes directly bind to TRAF6 proteins, a key player in immune signaling, thus protecting TRAF6 proteins from ubiquitination reactions that are involved in protein degradation. In addition, Kim and his colleagues successfully verified this IPMK-dependent immune control by employing short peptides which can specifically interfere with the binding between IPMK enzymes and TRAF6 proteins in macrophage cells. This research revealed a novel function of IPMK enzymes in the fine tuning of innate immune signaling networks, suggesting a new direction for developing therapeutics targeting serious medical conditions such as neuroinflammation, type 2 diabetes, as well as polymicrobial sepsis that are developed from uncontrolled host immune responses. This research was funded by the Ministry of Science, ICT and Future Planning. (Figure: Deletion of IPMK (inositol polyphosphate multikinase) in macrophages reduces the stability of TRAF6 protein which is the key to innate immune signaling, thereby blocking excessive inflammation in response to pathological bacterial infection.)
2017.05.11
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Professor Lee Recognized by the KMS as Best Paper Awardee
Professor Ji Oon Lee of the Department of Mathematical Sciences was selected as the 2017 Best Paper Awardee by the Korean Mathematical Society. The award will be presented during the KMS spring meeting on April 29. Dr. Lee is being honored for proving a necessary and sufficient condition for the Tracy-Wisdom law of Wigner matrices. In a paper titled ‘A Necessary and Sufficient Condition for Edge Universality of Wigner Matrices,’ he proposed a solution for one of the many unanswered problems in the field of random matrix theory that have existed for decades. The paper, co-authored with Professor Jun Yin at the University of Wisconsin – Madison, was published in the Duke Mathematical Journal in 2014. Professor Lee joined KAIST in 2010 after finishing his Ph.D. at Harvard University. He was named a ‘POSCI Science Fellow’ and received the ‘Young Scientist Award’ from the KMS in 2014.
2017.04.27
View 7675
Seeking a New Economic and Industrial Paradigm
The School of Humanities & Social Science will offer the open lecture course titled ‘Seeking a New Economic and Industrial Paradigm’ from May11 to June 7. This is part of a quarterly lecture series run by the school and open to the public. The open lecture is designed to provide opportunities for the public to identify future challenges and opportunities for Korea’s economy and industry. Experts in macroeconomics, finance, and global collaboration will provide glimpses of new directions for each sector as well as megatrends of emerging technologies on the heels of the 4th Industrial Revolution. Jin Hyuk Yoo from the Bank of Korea will speak on the ‘Outlook and Challenges of the Korean Economy.’ He will identify the current economic situation and explain how to build on sustainable long-term economic growth in the opening course. Won-Bin Lee of the Korea Institute for Industrial Economics & Trade will present on the ‘New Industrial Policy in the Era of the Fourth Industrial Revolution.’ His lecture will focus on fostering the local industry and creating its own ecosystem for furthering regional industries. Dong-Hoon Lee of Donga ST will speak on the implications that the Fourth Industrial Revolution will bring about in the medical industry. Won-Suk Choi of FnPricing will introduce the FN business model, presenting the risks and benefits of fintech in his lecture ‘Finance: Human and Technology.’ Jae-Hong Choi of the Institute of International Development Cooperation at Korea University will give a talk titled ‘Toward the World through Global Cooperation.’ He will present on the history of Korea’s global cooperation initiatives and the role of KOICA, introducing its emerging economic and industrial cooperation model. Professor Jeounghoon Kim, who is responsible for the public lecture program, said, “Korea now faces very diverse social economic and industrial challenges and we seem to be lost while searching for a solution. The public will have an opportunity to understand the current economic situation and its industrial implications.” For registration and more info, please visit http://hss.kaist.ac.kr.
2017.04.26
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Scholarship in Memory of Professor Shin Endowed by His Family
Professor Joong-Hoon Shin of the Graduate School of Nanoscience and Technology was touted as a genius young scientist who would take the lead in nanoscience technology. After earning degrees from Harvard and the Caltech, he was appointed at KAIST at age 27. He was the youngest professor ever appointed in Korea. Professor Shin’s outstanding research in the field of semiconductor nano-optics led him to be named as the ‘Scientist of the Year’ for three consecutive years from 2004 by the most prestigious scientist and technology organizations including the Korean Academy Science and Technology, the National Research Foundation of Korea, and the Korean government. However, a fatal car accident last September on the way home from a seminar in Gangwon Province took his life and a promising scholar’s research was left unfinished. He was 47 years old. Mrs. Young-Eun Hong, the widow of the late Professor Shin, made a 100 million KRW gift to KAIST to establish the ‘Joong-Hoon Shin Scholarship’ on April 7. The scholarship will provide financial assistance to outstanding students of physics and nanoscience. At the donation ceremony attended by President Sung-Chul Shin, Professor Shin’s colleagues and students, and family members, Mrs. Hong said, “My family would like to help young students achieve their dreams on behalf of my husband. I hope students will remember my husband’s passion and dedication toward his studies for a long time. He was a very hard worker.” Working at KAIST, Professor Shin made significant achievements in field of semiconductor nano-optics, specializing in silicon photonics and silicon nanocrystal structures. In particular, his research team gained attention reproducing the structure of ‘Morpho butterfly’ wings, which produce the same colors from various angles, using external light as a light source without extra power. Their research led to the creation of original technology dubbed the biomimetics reflective display and was published in Nature in 2012. Professor Shin’s legacy still endures. In February, a research team under Professor Shin-Hyun Kim of the Department of Chemical and Biomolecular Engineering includingthe late Professor Shin’s doctoral student Seung Yeol Lee, posthumously dedicated their research published on Advanced Materials to Professor Shin. ( click ) KAIST President Sung-Chul Shin, who is also a physicist, said “His passing is a great loss to the whole scientific and technology community, at home and abroad. But Joong-Hoon Shin scholarship will enable the growth and ensure the strength of nanoscience and its education at KAIST. We will uphold Professor Shin’s legacy by doing our best to make KAIST a world-leading university which can create global value.” Mrs. Hong said she will continue her husband’s academic legacy at his alma maters, Harvard and the Caltech, where he earned his BS in physics and his Ph.D. in applied physics respectively. She said she will start fundraising to establish the Joong-Hoon Shin Scholarship at Harvard and Caltech from July. (Mrs. Hong poses with President Sung-Chul Shin after donating 100 million KRW for establishing 'Joong-Hoon Shin Scholarship' in memory of her husband on April 7.)
2017.04.10
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Professor Won Do Heo Receives 'Scientist of the Month Award'
Professor Won Do Heo of the Department of Biological Sciences was selected as the “Scientist of the Month” for April 2017 by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea. Professor Heo was recognized for his suggestion of a new biological research method developing various optogenetics technology which controls cell function by using light. He developed the technology using lasers or LED light, without the need for surgery or drug administration, to identify the cause of diseases related to calcium ions such as Alzheimer’s disease and cancer. The general technique used in optogenetics, that control cells in the body with light, is the simple activation and deactivation of neurons. Professor Heo developed a calcium ion channel activation technique (OptoSTIM1) to activate calcium ions in the body using light. He also succeeded in increasing calcium concentrations with light to enhance the memory capacity of mice two-fold. Using this technology, the desired amount and residing time of calcium ion influx can be controlled by changing light intensity and exposure periods, enabling the function of a single cell or various cells in animal tissue to be controlled remotely. The experimental results showed that calcium ion influx can be activated in cells that are affected by calcium ions, such as normal cells, cancer cells, and human embryonic stem cells. By controlling calcium concentrations with light, it is possible to control biological phenomena, such as cellular growth, neurotransmitter transmission, muscle contraction, and hormone control. Professor Heo said, “Until now, it was standard to use optogenetics to activate neurons using channelrhodopsin. The development of this new optogenetic technique using calcium ion channel activation can be applied to various biological studies, as well as become an essential research technique in neurobiology. The “Scientist of the Month Award” is given every month to one researcher who made significant contributions to the advancement of science and technology with their outstanding research achievement. The awardee will receive prize money of ten million won.
2017.04.07
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Improving Silver Nanowires for FTCEs with Flash Light Interactions
Flexible transparent conducting electrodes (FTCEs) are an essential element of flexible optoelectronics for next-generation wearable displays, augmented reality (AR), and the Internet of Things (IoTs). Silver nanowires (Ag NWs) have received a great deal of attention as future FTCEs due to their great flexibility, material stability, and large-scale productivity. Despite these advantages, Ag NWs have drawbacks such as high wire-to-wire contact resistance and poor adhesion to substrates, resulting in severe power consumption and the delamination of FTCEs. A research team led by Professor Keon Jae Lee of the Materials Science and Engineering Department at KAIST and Dr. Hong-Jin Park from BSP Inc., has developed high-performance Ag NWs (sheet resistance ~ 5 Ω/sq, transmittance 90 % at λ = 550 nm) with strong adhesion on plastic (interfacial energy of 30.7 J∙m-2) using flash light-material interactions. The broad ultraviolet (UV) spectrum of a flash light enables the localized heating at the junctions of nanowires (NWs), which results in the fast and complete welding of Ag NWs. Consequently, the Ag NWs demonstrate six times higher conductivity than that of the pristine NWs. In addition, the near-infrared (NIR) of the flash lamp melted the interface between the Ag NWs and a polyethylene terephthalate (PET) substrate, dramatically enhancing the adhesion force of the Ag NWs to the PET by 310 %. Professor Lee said, “Light interaction with nanomaterials is an important field for future flexible electronics since it can overcome thermal limit of plastics, and we are currently expanding our research into light-inorganic interactions.” Meanwhile, BSP Inc., a laser manufacturing company and a collaborator of this work, has launched new flash lamp equipment for flexible applications based on the Professor Lee’s research. The results of this work entitled “Flash-Induced Self-Limited Plasmonic Welding of Ag NW Network for Transparent Flexible Energy Harvester (DOI: 10.1002/adma.201603473)” were published in the February 2, 2017 issue of Advanced Materials as the cover article. Professor Lee also contributed an invited review in the same journal of the April 3, 2017 online issue, “Laser-Material Interactions for Flexible Applications (DOI:10.1002/adma.201606586),” overviewing the recent advances in light interactions with flexible nanomaterials. References [1] Advanced Materials, February 2, 2017, Flash-Induced Self-Limited Plasmonic Welding of Ag NW network for Transparent Flexible Energy Harvester http://onlinelibrary.wiley.com/doi/10.1002/adma.201603473/epdf [2] Advanced Materials, April 3, 2017, Laser-Material Interactions for Flexible Applications http://onlinelibrary.wiley.com/doi/10.1002/adma.201606586/abstract For further inquiries on research: keonlee@kaist.ac.kr (Keon Jae Lee), hjpark@bsptech.co.kr (Hong-Jin Park) Picture 1: Artistic Rendtition of Light Interaction with Nanomaterials (This image shows flash-induced plasmonic interactions with nanowires to improve silver nanowires (Ag NWs).) Picture 2: Ag NW/PET Film (This picture shows the Ag NWs on a polyethylene terephthalate (PET) film after the flash-induced plasmonic thermal process.)
2017.04.05
View 9571
First Mutations in Human Life Discovered
The earliest mutations of human life have been observed by research team led by the Wellcome Trust Sanger Institute and their collaborators. Analyzing genomes from adult cells, the scientists could look back in time to reveal how each embryo developed. Research team of the Sanger Institute including Professor Young Seok Ju of the Graduate School of Medical Science and Engineering at KAIST published an article of “Somatic Mutations Reveal Asymmetric Cellular Dynamics in the Early Human Embryo” in Nature on March 22. The study shows that from the two-cell stage of the human embryo, one of these cells becomes more dominant than the other and leads to a higher proportion of the adult body. A longstanding question for researchers has been what happens in the very early human development as this has proved impossible to study directly. Now, researchers have analyzed the whole genome sequences of blood samples (collected from 279 individuals with breast cancer) and discovered 163 mutations that occurred very early in the embryonic development of those people. Once identified, the researchers used mutations from the first, second and third divisions of the fertilized egg to calculate which proportion of adult cells resulted from each of the first two cells in the embryo. They found that these first two cells contribute differently to the whole body. One cell gives rise to about 70 percent of the adult body tissues, whereas the other cell has a more minor contribution, leading to about 30percent of the tissues. This skewed contribution continues for some cells in the second and third generation too. Originally pinpointed in normal blood cells from cancer patients, the researchers then looked for these mutations in cancer samples that had been surgically removed from the patients during treatment. Unlike normal tissues composed of multiple somatic cell clones, a cancer develops from one mutant cell. Therefore, each proposed embryonic mutation should either be present in all of the cancer cells in a tumor, or none of them. This proved to be the case, and by using these cancer samples, the researchers were able to validate that the mutations had originated during early development. Dr. Young Seok Ju, first author from the Wellcome Trust Sanger Institute and KAIST, said: "This is the first time that anyone has seen where mutations arise in the very early human development. It is like finding a needle in a haystack. There are just a handful of these mutations, compared with millions of inherited genetic variations, and finding them allowed us to track what happened during embryogenesis." Dr. Inigo Martincorena, from the Sanger Institute, said: "Having identified the mutations, we were able to use statistical analysis to better understand cell dynamics during embryo development. We determined the relative contribution of the first embryonic cells to the adult blood cell pool and found one dominant cell - that led to 70 percent of the blood cells - and one minor cell. We also sequenced normal lymph and breast cells, and the results suggested that the dominant cell also contributes to these other tissues at a similar level. This opens an unprecedented window into the earliest stages of human development." During this study, the researchers were also able to measure the rate of mutation in early human development for the first time, up to three generations of cell division. Previous researchers had estimated one mutation per cell division, but this study measured three mutations for each cell doubling, in every daughter cell. Mutations during the development of the embryo occur by two processes - known as mutational signatures 1 and 5. These mutations are fairly randomly distributed through the genome, and the vast majority of them will not affect the developing embryo. However, a mutation that occurs in an important gene can lead to disease such as developmental disorders. Professor Sir Mike Stratton, lead author on the paper and Director of the Sanger Institute, said: "This is a significant step forward in widening the range of biological insights that can be extracted using genome sequences and mutations. Essentially, the mutations are archaeological traces of embryonic development left in our adult tissues, so if we can find and interpret them, we can understand human embryology better. This is just one early insight into human development, with hopefully many more to come in the future." (Figure 1. Detection of somatic mutations acquired in early human embryogenesis ) (Figure 2. Unequal contributions of early embryonic cells to adult somatic tissues )
2017.03.23
View 7217
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