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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 View 7390 -
Rh Ensemble Catalyst for Effective Automobile Exhaust Treatment
(from left: Professor Hyunjoo Lee and PhD candidate Hojin Jeong)
A KAIST research team has developed a fully dispersed Rh ensemble catalyst (ENS) that shows better performance than commercial diesel oxidation catalyst (DOC). This newly developed ENSs could improve low-temperature automobile exhaust treatment.
Precious metals have been used for various heterogeneous reactions, but it is crucial to maximize efficiency of catalysts due to their high cost. Single-atom catalysts (SACs) have received much attention because it is possible for all of the metal atoms to be used for reactions, yet they do not show catalytic activity for reactions that require ensemble sites.
Meanwhile, hydrocarbons, such as propylene (C3H6) and propane (C3H8) are typical automobile exhaust gas pollutants and must be converted to carbon dioxide (CO2) and water (H2O) before they are released as exhaust. Since the hydrocarbon oxidation reaction proceeds only during carbon-carbon (C-C) or carbon-hydrogen (C-H) bond cleavage, it is essential to secure the metal ensemble site for the catalytic reaction. Therefore, precious metal catalysts with high dispersion and ensemble sites are greatly needed.
To solve this issue, Professor Hyunjoo Lee from the Department of Chemical and Biomolecular Engineering and Professor Jeong Woo Han from POSTECH developed an Rh ensemble catalyst with 100% dispersion, and applied it to automobile after-treatment. Having a 100% dispersion means that every metal atom is used for the reaction since it is exposed on the surface.
SACs also have 100% dispersion, but the difference is that ENSs have the unique advantage of having an ensemble site with two or more atoms.
As a result of the experiment, the ENSs showed excellent catalytic performance in CO, NO, propylene, and propane oxidation at low temperatures. This complements the disadvantage of nanoparticle catalyst (NPs) that perform catalysis poorly at low temperatures due to low metal dispersion, or SACs without hydrocarbon oxidation.
In particular, the ENSs have superior low-temperature activity even better than commercial DOC, hence they are expected to be applied to automobile exhaust treatment.
Professor Lee said, “I believe that the ENSs have given academic contribution for proposing a new concept of metal catalysts, differentiating from conventional SACs and NPs. At the same time, they are of great value in the industry of exhaust treatment catalysts.”
This research, led by PhD candidate Hojin Jeong, was published in the Journal of the American Chemical Society on July 5.
Figure 1. Concept of Rh ensemble catalyst for automobile exhaust treatment
Figure 2. Structure and performance comparison of single-atom catalyst and ensemble catalyst
Figure 3. Energy-dispersive X-ray spectroscopy (EDS) mapping images for SAC, ENS, and NP, respectively (green, Eh; red, Ce)
2018.08.29 View 6468 -
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 View 5938 -
Metabolic Engineering of E. coli for the Secretory Production of Free Haem
Researchers of KAIST have defined a novel strategy for the secretory production of free haem using engineered Escherichia coli (E. coli) strains. They utilized the C5 pathway, the optimized downstream pathways, and the haem exporter to construct a recombinant micro-organism producing extracellular haem using fed-batch fermentation. This is the first report to extracellularly produce haem using engineered E. coli.
This strategy will expedite the efficient production of free haem to serve as a bioavailable iron-supplying agent and an important prosthetic group of multiple hemoproteins for medical uses. This study, led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, was published in Nature Catalysis on Aug. 28.
Haem, an organometallic compound complexed with a ferrous ion, is an essential molecule delivering oxygen in the blood of many animals. It is also a key component of electron transport chains responsible for the respiration of aerobic organisms including diverse bacteria. It is now being widely applied as a bioavailable iron-supplying agent in the healthcare and dietary supplement industries. The demand for haem and the need for the efficient production of this compound continue to grow.
Many previous researchers have attempted to produce free haem using engineered E. coli. However, none of the studies was successful in producing free haem extracellularly, requiring an additional step to extract the accumulated haem from cells for subsequent uses. The secretion of haem in the form of haem peptides or proteins also requires an extraction step to isolate the free haem from the secreted products. Thus, the secretory production of free haem is an important task for the economical production of haem that is suitable for human consumption.
Although some researchers could produce intracellular haem using recombinant E. coli strains, its final titer was extremely low, resulting from the use of sub-optimal metabolic pathways. Furthermore, the addition of the precursors L-glycine and succinate was deemed undesirable for massive industrial production. Thus, it is necessary to construct an optimized haem biosynthetic pathway to enable the efficient production of haem and examine the consequent secretion of free haem.
To address this issue, the KAIST team used multiple strategies to produce extracellular free haem by enhancing its biosynthesis in E. coli. First, the capacities of the C4 and C5 pathways to produce aminolevulinate (ALA) without feeding precursors were examined. After confirming the superior performance of the C5 pathway over the C4 pathway, the metabolic genes of the C5 pathway and downstream pathways for haem biosynthesis were overexpressed. Then, the metabolic pathways were optimized by adjusting the expression levels of the relevant genes and disrupting the putative haem degradation enzyme encoded by the yfeX gene.
Consequently, the resulting engineered strain secreted a significant amount of haem to the medium. Subsequent optimization of the cultivation conditions and the supplementation of nitrogen sources further increased both the titer of the total free haem and the amount of free haem secreted to the medium. Finally, the overexpression of the ccmABC genes encoding the haem exporter further enhanced the production and secretion of haem, producing the highest titer of haem both intracellularly and extracellularly from glucose.
Professor Lee said, “The eco-friendly and sustainable chemical industry is a key global agenda every nation faces. We are conducting research to bio-synthesize high concentrations, high yields, and high productivity in natural products. This novel technology will serve as an opportunity to advance the biochemical industry moving forward.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea ( leesy@kaist.ac.kr+82-42-350-3930).
2018.08.28 View 5338 -
Improved Efficiency of CQD Solar Cells Using an Organic Thin Film
(from left: Professor Jung-Yong Lee and Dr. Se-Woong Baek)
Recently, the power conversion efficiency (PCE) of colloidal quantum dot (CQD)-based solar cells has been enhanced, paving the way for their commercialization in various fields; nevertheless, they are still a long way from being commercialized due to their efficiency not matching their stability. In this research, a KAIST team achieved highly stable and efficient CQD-based solar cells by using an amorphous organic layer to block oxygen and water permeation.
CQD-based solar cells are light-weight, flexible, and they boost light harvesting by absorbing near-infrared lights. Especially, they draw special attention for their optical properties controlled efficiently by changing the quantum dot sizes. However, they are still incompatible with existing solar cells in terms of efficiency, stability, and cost. Therefore, there is great demand for a novel technology that can simultaneously improve both PCE and stability while using an inexpensive electrode material.
Responding to this demand, Professor Jung-Yong Lee from the Graduate School of Energy, Environment, Water and Sustainability and his team introduced a technology to improve the efficiency and stability of CQD-based solar cells.
The team found that an amorphous organic thin film has a strong resistance to oxygen and water. Using these properties, they employed this doped organic layer as a top-hole selective layer (HSL) for the PbS CQD solar cells, and confirmed that the hydro/oxo-phobic properties of the layer efficiently protected the PbS layer. According to the molecular dynamics simulations, the layer significantly postponed the oxygen and water permeation into the PbS layer. Moreover, the efficient injection of the holes in the layer reduced interfacial resistance and improved performance.
With this technology, the team finally developed CQD-based solar cells with excellent stability. The PCE of their device stood at 11.7% and maintained over 90% of its initial performance when stored for one year under ambient conditions.
Professor Lee said, “This technology can be also applied to QD LEDs and Perovskite devices. I hope this technology can hasten the commercialization of CQD-based solar cells.”
This research, led by Dr. Se-Woong Baek and a Ph.D. student, Sang-Hoon Lee, was published in Energy & Environmental Science on May 10.
Figure 1. The schematic of the equilibrated structure of the amorphous organic film
Figure 2. Schematic illustration of CQD-based solar cells and graphs showing their performance
2018.08.27 View 7311 -
Robotic Herding of a Flock of Birds Using Drones
A joint team from KAIST, Caltech, and Imperial College London, presents a drone with a new algorithm to shepherd birds safely away from airports
Researchers made a new algorithm for enabling a single robotic unmanned aerial vehicle to herd a flock of birds away from a designated airspace. This novel approach allows a single autonomous quadrotor drone to herd an entire flock of birds away without breaking their formation.
Professor David Hyunchul Shim at KAIST in collaboration with Professor Soon-Jo Chung of Caltech and Professor Aditya Paranjape of Imperial College London investigated the problem of diverting a flock of birds away from a prescribed area, such as an airport, using a robotic UVA. A novel boundary control strategy called the m-waypoint algorithm was introduced for enabling a single pursuer UAV to safely herd the flock without fragmenting it.
The team developed the herding algorithm on the basis of macroscopic properties of the flocking model and the response of the flock. They tested their robotic autonomous drone by successfully shepherding an entire flock of birds out of a designated airspace near KAIST’s campus in Daejeon, South Korea. This study is published in IEEE Transactions on Robotics.
“It is quite interesting, and even awe-inspiring, to monitor how birds react to threats and collectively behave against threatening objects through the flock. We made careful observations of flock dynamics and interactions between flocks and the pursuer. This allowed us to create a new herding algorithm for ideal flight paths for incoming drones to move the flock away from a protected airspace,” said Professor Shim, who leads the Unmanned Systems Research Group at KAIST.
Bird strikes can threaten the safety of airplanes and their passengers. Korean civil aircraft suffered more than 1,000 bird strikes between 2011 and 2016. In the US, 142,000 bird strikes destroyed 62 civilian airplanes, injured 279 people, and killed 25 between 1990 and 2013. In the UK in 2016, there were 1,835 confirmed bird strikes, about eight for every 10,000 flights. Bird and other wildlife collisions with aircraft cause well over 1.2 billion USD in damages to the aviation industry worldwide annually. In the worst case, Canadian geese knocked out both engines of a US Airway jet in January 2009. The flight had to make an emergency landing on the Hudson River.
Airports and researchers have continued to reduce the risk of bird strikes through a variety of methods. They scare birds away using predators such as falcons or loud noises from small cannons or guns. Some airports try to prevent birds from coming by ridding the surrounding areas of crops that birds eat and hide in.
However, birds are smart. “I was amazed with the birds’ capability to interact with flying objects. We thought that only birds of prey have a strong sense of maneuvering with the prey. But our observation of hundreds of migratory birds such as egrets and loons led us to reach the hypothesis that they all have similar levels of maneuvering with the flying objects. It will be very interesting to collaborate with ornithologists to study further with birds’ behaviors with aerial objects,” said Professor Shim. “Airports are trying to transform into smart airports. This algorithm will help improve safety for the aviation industry. In addition, this will also help control avian influenza that plagues farms nationwide every year,” he stressed.
For this study, two drones were deployed. One drone performed various types of maneuvers around the flocks as a pursuer of herding drone, while a surveillance drone hovered at a high altitude with a camera pointing down for recording the trajectories of the pursuer drone and the birds.
During the experiments on egrets, the birds made frequent visits to a hunting area nearby and a large number of egrets were found to return to their nests at sunset. During the time, the team attempted to fly the herding drone in various directions with respect to the flock.
The drone approached the flock from the side. When the birds noticed the drone, they diverted from their original paths and flew at a 45˚ angle to their right. When the birds noticed the drone while it was still far away, they adjusted their paths horizontally and made smaller changes in the vertical direction. In the second round of the experiment on loons, the drone flew almost parallel to the flight path of a flock of birds, starting from an initial position located just off the nominal flight path. The birds had a nominal flight speed that was considerably higher than that of the drone so the interaction took place over a relatively short period of time.
Professor Shim said, “I think we just completed the first step of the research. For the next step, more systems will be developed and integrated for bird detection, ranging, and automatic deployment of drones.” “Professor Chung at Caltech is a KAIST graduate. And his first student was Professor Paranjape who now teaches at Imperial. It is pretty interesting that this research was made by a KAIST faculty member, an alumnus, and his student on three different continents,” he said.
(Figure A. Case 1: drone approaches the herd with sufficient distance to induce horizontal deviation)
(Figure B. Case 2: drone approaches the herd abruptly to cause vertical deviation)
2018.08.23 View 8917 -
'K-FLEX' Makes a Splash as a Flexible Endoscopic Surgical Robot
( Robot arms perform an incision during an ex-vivo test on a porcine gallbladder.)
K-FLEX, a flexible endoscopic surgical robot developed by the KAIST Future Medical Robotics Research Center, opens a new chapter for minimally invasive robot-assisted surgery with its precision control of 3.7 mm diameter robotic arms. The two arms, placing at the end of flexible endoscopes, highlight impeccable precision control and robust mini-joint design technologies. While cruising through the complicated inner body pliably, it carries out procedures on the spot with its robotic arms.
The research team under Professor Dong-Soo Kwon recently tested the device in-vivo, conducting a complicated endoscopic procedure dissecting a porcine gallbladder in collaboration with Professor Dae-Kyung Son of the National Cancer Center. The arms successfully manipulated the tissue safely.
During the test, K-FLEX, inserted through an incision in the navel, snaked through the narrow passages of the complicated inner organs. When reaching the desired spot, one of the robot arms pushed aside and held up the nearby tissue to secure proper vision and space for the procedure. Meanwhile, a cautery needle mounted at the tip of the other hand removed the lesion tissue on the gallbladder. The tiny camera installed at the front of the robot arms relayed the internal conditions. The full procedure was able to be monitored from the master console.
The two arms are placed onto 4.2 mm internal channels of an endoscope which is 17 mm in diameter. The arms can be deployable forward and backward and are extendable up to 7 cm for performing procedures.
K-FLEX is made of domestically produced components, except for the endoscopic module. It will expand new medical robotics research while offering novel therapeutic capabilities for endoscopes.
Flexible endoscopes are very promising for surgical applications because they can treat areas thought to be difficult to reach, such as the posterior side of an organ. Current rigid-type laparoscopic tools could not reach a lesion if it occurs in such serpentine and complicated areas. However, this flexible endoscopic surgery robot will bypass obstacles to reach the troubled area.
The ability to seamlessly integrate effective actuation into millimeter-scale deployable mechanisms fits well with minimally invasive surgical procedures. This flexible endoscopic surgery robot, only half the size of current laparoscopic surgical robots, is deployable into natural orifices such as the mouth, anus, and vagina without requiring external incisions. Laparoscopic devices and robots require at least three to four external incisions to insert the devices; however, the applicability of internal incisions reduces the possibility of complications arousing from excessive bleeding and bacterial infections.
Despite these advantages, it has remained challenging to manipulate the robotic arms of flexible endoscopes with integrated grabbing force, flexibility, and multiple degrees of freedom for clinical environments.
The team focused on smaller but smarter devices. Dr. Min-Ho Hwang, a principal researcher of K-FLEX, said that developing tiny robots that are able to generate the necessary forces without compromising safety was the challenge. They created a robust but smaller-joint technology that can exert a relatively greater force even into millimeter scale.
Professor Kwon said, “K-FLEX is the first flexible endoscopic surgery robot in Korea. We already confirmed the clinical adaptation through ex vivo tests and will see complete commercialization in two to three years.” The team believes K-FLEX will be very effective for surgery on incipient cancer cells in the stomach, colon, and thyroid.
Professor Kwon and his eight researchers recently established a tech start-up called EasyEndo Surgical Inc. with these core technologies. In June, K-FLEX won the ‘Best Application Award’ and the ‘Overall Winner’ at the Surgical Robot Challenge 2018 held at Imperial College London. The Korea Research Foundation funded the research on K-FLEX.
(The team conducts a procedure using K-FLEX, flexible endoscopic surgical robot.)
2018.08.17 View 7847 -
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 View 8201 -
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 View 11000 -
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 View 7357 -
Computer Simulation Identifies a Key Principle for Next-generation Carbon Fibers
(from left: Professor Yong-Hoon Kim and PhD candidate Juho Lee)
Performing state-of-the-art computer simulations, a KAIST research team identified an atomistic design principle to produce high-quality, next-generation carbon fibers.
Carbon fibers are light-weight yet excellent in mechanical strength and thermal resistance. Boasting these properties, they can be diversely applied in high-technology sectors, including automotive, aerospace, and nuclear engineering.
They are produced from a polymer precursor through a series of spinning, stabilization, and carbonization processes. However, there is a major obstacle to producing high-quality carbon fibers. That is, when there exist ill-defined regions within the polymer matrixes, they result in disorder and defects within the produced carbon fibers.
As a solution to this problem, it was proposed that the introduction of carbon nanotubes (CNT) could enhance polymer orientation and crystallization. However, although the alignment geometry of the CNT-polymer interface apparently affects the quality of produced fibers, the atomistic understanding of the CNT-polymer interface has been so far lacking, hindering further developments.
To clarify the nature of CNT-polymer interactions, Professor Yong-Hoon Kim from the Graduate School of Energy, Environment, Water and Sustainability and his team employed a multiscale approach that combines first-principles density functional theory (DFT) calculations and force-fields molecular dynamics (MD) simulations and revealed the unique structural and electronic characteristics of polymer-CNT interfaces.
Here, they studied polyacrylonitrile (PAN)-CNT hybrid structures as a representative case of polymer-CNT composites. PAN is the most common polymer precursor, taking more than 90% of carbon fiber production.
Based on their DFT calculations, the team showed that the lying-down PAN configurations give a larger PAN-CNT binding energy than their standing-up counterparts. Moreover, maximizing the lying-down PAN configuration was shown to allow linear alignments of PANs on CNT, enabling the desirable ordered long-range PAN-PAN packing.
They also identified the CNT curvature as another significant factor, giving the largest PAN-CNT binding energy in the zero-curvature graphene limit. Conducting large-scale MD simulations, they then demonstrated that graphene nanoribbons are a promising carbon nano-reinforcement candidate by explicitly showing its strong propensity to induce linear alignments of PANs adsorbed on them.
Professor Kim said, “This research can be an exemplary case where the quantum mechanical simulations identify basic principles for developing advanced materials. Computer simulation studies will play an increasingly greater role thanks to the advances in the simulation theory and computer performance.”
This research, carried out by the PhD candidate Juho Lee, was published in the inside back cover of Advanced Functional Materials on April 11.
Figure 1. Inside back cover of Advanced Functional Materials
Figure 2. Research outline
2018.08.03 View 7905 -
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 View 11534