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Mussel-Inspired Defect Engineering Enhances the Mechanical Strength of Graphene Fibers
Researchers demonstrated the mussel-inspired reinforcement of graphene fibers for the improvement of different material properties. A research group under Professor Sang Ouk Kim applied polydopamine as an effective infiltrate binder to achieve high mechanical and electrical properties for graphene-based liquid crystalline fibers. This bio-inspired defect engineering is clearly distinguishable from previous attempts with insulating binders and proposes great potential for versatile applications of flexible and wearable devices as well as low-cost structural materials. The two-step defect engineering addresses the intrinsic limitation of graphene fibers arising from the folding and wrinkling of graphene layers during the fiber-spinning process. Bio-inspired graphene-based fiber holds great promise for a wide range of applications, including flexible electronics, multifunctional textiles, and wearable sensors. In 2009, the research group discovered graphene oxide liquid crystals in aqueous media while introducing an effective purification process to remove ionic impurities. Graphene fibers, typically wet-spun from aqueous graphene oxide liquid crystal dispersion, are expected to demonstrate superior thermal and electrical conductivities as well as outstanding mechanical performance. Nonetheless, owing to the inherent formation of defects and voids caused by bending and wrinkling the graphene oxide layer within graphene fibers, their mechanical strength and electrical/thermal conductivities are still far below the desired ideal values. Accordingly, finding an efficient method for constructing the densely packed graphene fibers with strong interlayer interaction is a principal challenge. Professor Kim's team focused on the adhesion properties of dopamine, a polymer developed with the inspiration of the natural mussel, to solve the problem. This functional polymer, which is studied in various fields, can increase the adhesion between the graphene layers and prevent structural defects. Professor Kim’s research group succeeded in fabricating high-strength graphene liquid crystalline fibers with controlled structural defects. They also fabricated fibers with improved electrical conductivity through the post-carbonization process of polydopamine. Based on the theory that dopamine with subsequent high temperature annealing has a similar structure with that of graphene, the team optimized dopamine polymerization conditions and solved the inherent defect control problems of existing graphene fibers. They also confirmed that the physical properties of dopamine are improved in terms of electrical conductivity due to the influence of nitrogen in dopamine molecules, without damaging the conductivity, which is the fundamental limit of conventional polymers. Professor Kim, who led the research, said, "Despite its technological potential, carbon fiber using graphene liquid crystals still has limits in terms of its structural limitations." This technology will be applied to composite fiber fabrication and various wearable textile-based application devices." This work, in which Dr. In-Ho Kim participated as first author was selected as a front cover paper of Advanced Materials on October 4. This research was supported by the National Creative Research Initiative (CRI) Center for Multi-Dimensional Directed Nanoscale Assembly and the Nanomaterial Technology Development Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT. Figure 1. Cross-section SEM image of pure graphene fiber (left) and that of graphene fiber after two-stage defect control using polydopamine (middle and right).
2018.10.23
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Dr. Sejeong Kim Recognized as Excellent Young Scientist
(Dr. Sejeong Kim) Dr. Sejeong Kim, a postdoctoral research associate in the School of Mathematical and Physical Sciences at the University of Technology Sydney was honored to receive the Excellence Award for a Young Scientist by the Korea Federation of Women’s Science & Technology Association (KOFWST). The award ceremony will be held on October 31 in Seoul. KOFWST recognizes ten promising young female scientists and engineers every year who show significant potential, passion, and remarkable achievement in their work. The awardees are selected among those who finished their degree within the previous five years. Dr. Kim earned her Ph.D. in physics at KAIST in 2014 and was selected as the winner in the field of physics in recognition of her outstanding research activities in photonics. Dr. Kim conducted various research activities in the field of photonics and was published in high impact journals including Nano Letters and Advanced materials. In July, she developed the first photonic cavity from van der Waals materials and published the study in Nature Communications titled “Photonic Crystal Cavities from Hexagonal Boron Nitride.” At UTS, she carries out research activities supervised by Professor Igor Aharonovich and has engaged in many science outreach activities.
2018.10.18
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Flexible Piezoelectric Acoustic Sensors for Speaker Recognition
A KAIST research team led by Professor Keon Jae Lee from the Department of Material Science and Engineering has developed a machine learning-based acoustic sensor for speaker recognition. Acoustic sensors were spotlighted as one of the most intuitive bilateral communication devices between humans and machines. However, conventional acoustic sensors use a condenser-type device for measuring capacitance between two conducting layers, resulting in low sensitivity, short recognition distance, and low speaker recognition rates. The team fabricated a flexible piezoelectric membrane by mimicking the basilar membrane in the human cochlear. Resonant frequencies vibrate corresponding regions of the trapezoidal piezoelectric membrane, which converts voice to electrical signal with a highly sensitive self-powered acoustic sensor. This multi-channel piezoelectric acoustic sensor exhibits sensitivity more than two times higher and allows for more abundant voice information compared to conventional acoustic sensors, which can detect minute sounds from farther distances. In addition, the acoustic sensor can achieve a 97.5% speaker recognition rate using a machine learning algorithm, reducing by 75% error rate than the reference microphone. AI speaker recognition is the next big thing for future individual customized services. However, conventional technology attempts to improve recognition rates by using software upgrades, resulting in limited speaker recognition rates. The team enhanced the speaker recognition system by replacing the existing hardware with an innovative flexible piezoelectric acoustic sensor. Further software improvement of the piezoelectric acoustic sensor will significantly increase the speaker and voice recognition rate in diverse environments. Professor Lee said, “Highly sensitive self-powered acoustic sensors for speaker recognition can be used for personalized voice services such as smart home appliances, AI secretaries, always-on IoT, biometric authentication, and FinTech.” These research “Basilar Membrane-Inspired Self-Powered Acoustic Sensor” and “Machine Learning-based Acoustic Sensor for Speaker Recognition” were published in the September 2018 issue of Nano Energy. Firgure 1: A flexible piezoelectric acoustic sensor mimicking the human cochlear. Figure 2: Speaker recognition with a machine learning algorithm.
2018.10.04
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The 1st Korea Toray Science and Technology Awardee, Prof. Sukbok Chang
(Distinguished Professor Sukbok Chang from the Department of Chemistry) The Korea Toray Science Foundation (KTSF) awarded the first Korea Toray Science Technology Award in basic science to Distinguished Professor Sukbok Chang from the Department of Chemistry on September 19. KTSF was established in January 2018, and its award goes to researchers who have significantly contributed to the development of chemistry and materials research with funds to support research projects. Distinguished Professor Chang has devoted himself in organocatalysis research; in particular, his work on catalysts for effective lactam formation, which was an intricate problem, received great attention. The award ceremony will take place in The Federation of Korean Industries Hall on October 31. KTFS board members, judges, and the CEO of Toray Industries Akihiro Nikkaku will attend the ceremony. Also, Dr. Ryoji Noyori, the Nobel Laureate in Chemistry, will give a talk on the role of chemistry and creative challenges as a researcher.
2018.10.04
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Spray Coated Tactile Sensor on a 3-D Surface for Robotic Skin
Robots will be able to conduct a wide variety of tasks as well as humans if they can be given tactile sensing capabilities. A KAIST research team has reported a stretchable pressure insensitive strain sensor by using an all solution-based process. The solution-based process is easily scalable to accommodate for large areas and can be coated as a thin-film on 3-dimensional irregularly shaped objects via spray coating. These conditions make their processing technique unique and highly suitable for robotic electronic skin or wearable electronic applications. The making of electronic skin to mimic the tactile sensing properties of human skin is an active area of research for various applications such as wearable electronics, robotics, and prosthetics. One of the major challenges in electronic skin research is differentiating various external stimuli, particularly between strain and pressure. Another issue is uniformly depositing electrical skin on 3-dimensional irregularly shaped objects. To overcome these issues, the research team led by Professor Steve Park from the Department of Materials Science and Engineering and Professor Jung Kim from the Department of Mechanical Engineering developed electronic skin that can be uniformly coated on 3-dimensional surfaces and distinguish mechanical stimuli. The new electronic skin can also distinguish mechanical stimuli analogous to human skin. The structure of the electronic skin was designed to respond differently under applied pressure and strain. Under applied strain, conducting pathways undergo significant conformational changes, considerably changing the resistance. On the other hand, under applied pressure, negligible conformational change in the conducting pathway occurs; e-skin is therefore non-responsive to pressure. The research team is currently working on strain insensitive pressure sensors to use with the developed strain sensors. The research team also spatially mapped the local strain without the use of patterned electrode arrays utilizing electrical impedance tomography (EIT). By using EIT, it is possible to minimize the number of electrodes, increase durability, and enable facile fabrication onto 3-dimensional surfaces. Professor Park said, “Our electronic skin can be mass produced at a low cost and can easily be coated onto complex 3-dimensional surfaces. It is a key technology that can bring us closer to the commercialization of electronic skin for various applications in the near future.” The result of this work entitled “Pressure Insensitive Strain Sensor with Facile Solution-based Process for Tactile Sensing Applications” was published in the August issue of ACS Nano as a cover article. (Figure: Detecting mechanical stimuli using electrical impedance tomography.)
2018.09.21
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Understanding Epilepsy in Pediatric Tumors; New Therapeutic Target of Intractable Epilepsy Identified
Pediatric brain tumors are characterized by frequent complications due to intractable epilepsy compared to adult brain tumors. However, the genetic cause of refractory epilepsy in pediatric brain tumors has not been elucidated yet, and it is difficult to treat patients because the tumors do not respond to existing antiepileptic drugs and debilitate children’s development. A research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors. Their research results were published online in Nature Medicine on September 17. The research team studied patients’ tissue diagnosed with ganglioglioma (GG), one of the main causes of tumor-associated intractable epilepsy, and found that the BRAF V600E somatic mutation is involved in the development of neural stem cells by using deep DNA sequencing. This mutation was carried out in an animal model to reproduce the pathology of GG and to observe seizures to establish an animal model for the treatment of epileptic seizures caused by pediatric brain tumors. Using immunohistochemical and transcriptome analysis, they realized that the BRAF V600E mutation that arose in early progenitor cells during embryonic brain formation led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to a high proliferation of glial lineage cells exhibiting the mutation. Notably, researchers found that seizures in mice were significantly alleviated by intraventricular infusion of the BRAF V600E inhibitor, Vemurafenib, a clinical anticancer drug. The authors said, “Our study offers the first direct evidence that the BRAF somatic mutation arising from neural stem cells plays a key role in epileptogenesis in the brain tumor. This study also showed a new therapeutic target for tumor-associated epileptic disorders.” In collaboration with the KAIST startup company, SoVarGen, the research team is currently developing innovative therapeutics for epileptic seizures derived from pediatric brain tumors. This study was supported by the Suh Kyungbae Foundation (SUHF) and the Citizens United for Research in Epilepsy. (Figure: Preoperative and postoperative brain MRI (left panel), tumor H&E (right upper panel) and GFAP immunohistochemical (right lower panel) staining images from a patient with ganglioglioma (GG231) carrying the BRAFV600E mutation. The white arrow and the black arrowhead indicate the brain tumor and a dysplastic neuron, respectively.)
2018.09.19
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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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Levitating 2D Semiconductor for Better Performance
(from top: Professor Yeon Sik Jung and PhD candidate Soomin Yim) Atomically thin 2D semiconductors have been drawing attention for their superior physical properties over silicon semiconductors; nevertheless, they are not the most appealing materials due to their structural instability and costly manufacturing process. To shed some light on these limitations, a KAIST research team suspended a 2D semiconductor on a dome-shaped nanostructure to produce a highly efficient semiconductor at a low cost. 2D semiconducting materials have emerged as alternatives for silicon-based semiconductors because of their inherent flexibility, high transparency, and excellent carrier transport properties, which are the important characteristics for flexible electronics. Despite their outstanding physical and chemical properties, they are oversensitive to their environment due to their extremely thin nature. Hence, any irregularities in the supporting surface can affect the properties of 2D semiconductors and make it more difficult to produce reliable and well performing devices. In particular, it can result in serious degradation of charge-carrier mobility or light-emission yield. To solve this problem, there have been continued efforts to fundamentally block the substrate effects. One way is to suspend a 2D semiconductor; however, this method will degrade mechanical durability due to the absence of a supporter underneath the 2D semiconducting materials. Professor Yeon Sik Jung from the Department of Materials Science and Engineering and his team came up with a new strategy based on the insertion of high-density topographic patterns as a nanogap-containing supporter between 2D materials and the substrate in order to mitigate their contact and to block the substrate-induced unwanted effects. More than 90% of the dome-shaped supporter is simply an empty space because of its nanometer scale size. Placing a 2D semiconductor on this structure creates a similar effect to levitating the layer. Hence, this method secures the mechanical durability of the device while minimizing the undesired effects from the substrate. By applying this method to the 2D semiconductor, the charge-carrier mobility was more than doubled, showing a significant improvement of the performance of the 2D semiconductor. Additionally, the team reduced the price of manufacturing the semiconductor. In general, constructing an ultra-fine dome structure on a surface generally involves costly equipment to create individual patterns on the surface. However, the team employed a method of self-assembling nanopatterns in which molecules assemble themselves to form a nanostructure. This method led to reducing production costs and showed good compatibility with conventional semiconductor manufacturing processes. Professor Jung said, “This research can be applied to improve devices using various 2D semiconducting materials as well as devices using graphene, a metallic 2D material. It will be useful in a broad range of applications, such as the material for the high speed transistor channels for next-generation flexible displays or for the active layer in light detectors.” This research, led by PhD candidate Soomin Yim, was published in Nano Letters in April. Figure 1. Image of a 2D semiconductor using dome structures
2018.08.28
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Flexible Drug Delivery Microdevice to Advance Precision Medicine
(Schematic view of flexible microdevice: The flexible drug delivery device for controlled release fabricated via inorganic laser lift off.) A KAIST research team has developed a flexible drug delivery device with controlled release for personalized medicine, blazing the path toward theragnosis. Theragnosis, an emerging medical technology, is gaining attention as key factor to advance precision medicine for its featuring simultaneous diagnosis and therapeutics. Theragnosis devices including smart contact lenses and microneedle patches integrate physiological data sensors and drug delivery devices. The controlled drug delivery boasts fewer side-effects, uniform therapeutic results, and minimal dosages compared to oral ingestion. Recently, some research groups conducted in-human applications of controlled-release bulky microchips for osteoporosis treatment. However they failed to demonstrate successful human-friendly flexible drug delivery systems for controlled release. For this microdevice, the team under Professor Daesoo Kim from the Department of Biological Science and Professor Keon Jae Lee from the Department of Materials Science and Engineering, fabricated a device on a rigid substrate and transferred a 50 µm-thick active drug delivery layer to the flexible substrate via inorganic laser lift off. The fabricated device shows mechanical flexibility while maintaining the capability of precise administration of exact dosages at desired times. The core technology is to produce a freestanding gold capping layer directly on top of the microreservoir with the drugs inside, which had been regarded as impossible in conventional microfabrication. The developed flexible drug delivery system can be applied to smart contact lenses or the brain disease treatments by implanting them into cramped and corrugated organs. In addition, when powered wirelessly, it will represent a novel platform for personalized medicine. The team already proved through animal experimentation that treatment for brain epilepsy made progress by releasing anti-epileptic medication through the device. Professor Lee believes the flexible microdevice will further expand the applications of smart contact lenses, therapeutic treatments for brain disease, and subcutaneous implantations for daily healthcare system. This study “Flexible Wireless Powered Drug Delivery System for Targeted Administration on Cerebral Cortex” was described in the June online issue of Nano Energy. (Photo: The flexible drug delivery device for contolled relase attached on a glass rod.)
2018.08.13
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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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How to Trigger Innate Fear Response?
(Figure:This illustration describes how ACC-BLA circuit controls innate freezing response depending on its activity level.) When animals encounter danger, they usually respond to the situation in one of two ways: to freeze or to flee. How do they make this quick decision in a life or death moment? According to KAIST neuroscientists, there are two types of fear: learned versus innate. The latter is known to be induced without any prior experience and is thus naturally encoded in the brain. A research team under Professor Jin-Hee Han in the Department of Biological Sciences identified the brain circuit responsible for regulating the innate fear response. The study, which appeared in the July 24 issue of Nature Communications represents a significant step toward understanding how the neural circuits in the prefrontal cortex create behavioral responses to external threats. This also represents a new paradigm in therapeutic development for fear-related mental disorders. Responses of freezing or fleeing when facing external threats reflect behavioral and physiological changes in an instinctive move to adapt to the new environment for survival. These responses are controlled by the emotional circuit systems of the brain and the malfunction of this circuit leads to fear-related disorders. The anterior cingulate cortex (ACC) is a sub-region within the prefrontal cortex, comprising a part of the brain circuitry that regulates behavioral and physiological fear responses. This area is capable of high-order processing of the perceived sensory information and conveys ‘top-down’ information toward the amygdala and brainstem areas, known as the response outlet. Many studies have already demonstrated that the brain regions in the prefrontal cortex regulate the response against learned threats. However, it has been unknown how innate responses against fear are encoded in the neural circuits in the prefrontal cortex. Dr. Jinho Jhang, the lead author of the study explains how the team achieved their key idea. “Many overseas studies have already proved that the prefrontal cortex circuit works to regulate the fear response. However, researchers have paid little attention to the innate response against predators. Professor Han suggested we do research on the instinctive fear response instead of the learned response. We particularly focused on the anterior cingulate region, which has been connected with memory, pain, and sympathy, but not the fear response itself. Since we turned in this new direction, we have accumulated some significant data,” said Dr. Jhang. For this study, Professor Han’s team investigated how mice react when exposed to the olfactory stimuli of predators. Based on the results of optogenetic manipulation, neural circuit tracing, and ex vivo slice electrophysiology experiments, the team demonstrated that the anterior cingulate cortex and its projection input to the basolateral amygdala play a role in the inhibitory regulation of innate fear responses to predators’ odors in mice. Professor Han believes these results will extend the understanding of how instinctive fear responses can be encoded in our brain circuits. “Our findings will help to develop therapeutic treatments for mental disorders aroused from fear such as panic disorders and post-traumatic stress disorder,” said Professor Han.
2018.08.08
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A Breakthrough for Understanding Glioblastoma: Origin Cells for Deadly Brain Tumors Identified
Figure 1. The pattern of GBM genesis is similar to that of firework. The bottom canon represents the first occurrence of the SVZ mutated cell. A new study by KAIST researchers identified where the mutation causing glioblastoma starts. According to the study, neural stem cells away from the tumor mass are the cells of origin that contain mutation drivers for glioblastoma, one of the most aggressive brain tumor. This breakthrough research, reported in Nature on August 1, gives insights for understanding why glioblastomas almost always grow back, even after surgery, and suggests novel ways to treat glioblastoma, which was previously thought to be incurable. Like most cancers, glioblastoma is treated with surgery to remove as much of the tumor as possible, then radiation and chemotherapy. However, it almost always returns in less than a year and its median survival time is only 15 months. Precision therapeutic approaches targeting tumors themselves didn’t lead to any breakthroughs. Professor Jeong Ho Lee’s team at the Graduate School of Medical Science and Engineering described direct genetic evidence through the deep sequencing of all triple-matched samples: normal SVZ tissue away from the tumor mass, tumor tissue, and normal cortical tissue. The research team studied 28 patients with glioblastomas and other types of brain tumors who underwent supra-total resection or other surgical resections of tumors, providing access to normal subventricular zone (SVZ) tissue (where neural stem cells are located) away from the tumor mass. The researchers used various deep and single cell sequencing technologies to conduct comparative DNA analysis on the samples from the patient’s SVZ tissue and tumors. They reported that normal SVZ tissue away from the tumor in 56.3% of patients with glioblastoma already contained low-level glioblastoma driver mutations that were observed at high levels in their matching tumors. Furthermore, the research team generated a genome edited mouse carrying glioblastoma mutations in the SVZ and showed that neural stem cells with mutations migrate from the SVZ lead to the development of glioblastomas in distant brain regions. (See the image below) Professor Lee conducted this study in collaboration with Professor Seok-Gu Kang of the Brain Tumor Center at Severance Hospital of Yonsei University. He said, “It’s easier to understand when we compare it to fireworks. Every flare flying around sky can be likened to cancer cells even though the fireworks are triggered on the ground. We found the trigger.” The identification of this mutation pathway of glioblastomas will lead to a new paradigm for therapeutic strategies. He added, “Now, we can focus on interrupting the recurrence and evolution of glioblastomas.” Professor Lee has investigated mutations arising in the brain for a decade. He is developing innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma at a tech-startup, SoVarGen. “All technologies we used during the research were transferred to the company. This research gave us very good momentum to reach the next phase of our startup,” he remarked. Figure 2. Genetic analysis of tumor-free SVZ tissue and matching tumor tissue from GBM patients. Figure 3. Glioma progression in genome edited mice carrying GBM mutations in the SVZ
2018.08.02
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