Science
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Discovery of New Therapeutic Targets for Alzheimer's Disease
A Korean research team headed by Professor Dae-Soo Kim of Biological Sciences at KAIST and Dr. Chang-Jun Lee from the Korea Institute of Science and Technology (KIST) successfully identified that reactive astrocytes, commonly observed in brains affected by Alzheimer’s disease, produce abnormal amounts of inhibitory neurotransmitter gamma-Aminobutyric acid (GABA) in reaction to the enzyme Monoamine oxidase B (Mao-B) and release GABA through the Bestrophin-1 channel to suppress the normal signal transmission of brain nerve cells.
By suppressing the GABA production or release from reactive astrocytes, the research team was able to restore the model mice's memory and learning impairment caused by Alzheimer’s disease. This discovery will allow the development of new drugs to treat Alzheimer’s and other related diseases.
The research result was published in the June 29, 2014 edition of Nature Medicine (Title: GABA from Reactive Astrocytes Impairs Memory in Mouse Models of Alzheimer’s Disease).
For details, please read the article below:
Technology News, July 10, 2014
"Discovery of New Drug Targets for Memory Impairment in Alzheimer’s Disease"
http://technews.tmcnet.com/news/2014/07/10/7917811.htm
2014.07.16 View 8381 -
Artificial Antibody-based Therapeutic Candidate for Lung Cancer Developed
Professor Hak-Sung Kim of Biological Sciences at KAIST publishes a cover article on artificial antibody in "Molecular Therapy".
Repebody-based lung cancer therapeutic drug candidate developed Repebody-based protein demonstrates the possibility of the development of a new drug
KAIST Biological Sciences Department’s Professor Hak-Sung Kim, in collaboration with Professor Eun-Kyung Cho from the College of Medicine at Chungnam National University, has successfully developed an artificial antibody-based, or repebody, cancer therapeutic candidate. These research results were published as a cover paper of the July edition of Molecular Therapy.
The repebody developed by Professor Kim and his team strongly binds to interleukin-6, a cancer-causing factor. It has also been confirmed that the repebody can significantly inhibit the proliferation of cancer cells in non-small-cell lung cancer animal model.
Numerous multinational pharmaceutical and biotechnology companies have invested astronomical amounts of money in research for the development of protein therapeutics with low side effects and high efficacy. More than 20 kinds of such therapeutics are currently under clinical trials, and over 100 drugs are under clinical demonstration. Among these, the majority is antibody-based therapeutics, and most of the investments are heavily concentrated in this field. However, antibody production cost is very high because it has large molecular weights and complex structural properties, and this makes it difficult to engineer. Consequently, the development costs a great deal of time and money.
In order to overcome the existing limitations of antibody-based therapeutics, Professor Kim and his team have developed a new artificial antibody, or repebody, which was published in Proceedings of the National Academy of Sciences (PNAS) in 2012. Based on this research, they have succeeded in developing a therapeutic candidate for treating non-small-cell lung cancer with a specifically strong cohesion to the cancer-causing factor, interleukin-6.
Interleukin-6 is a crucial substance within the body that is involved in immune and inflammatory-related signals. When abnormally expressed, it activates various carcinogenic pathways and promotes tumor growth and metastasis. Because of its importance, multinational pharmaceutical companies are heavily investing in developing therapeutics that can inhibit the signaling of interleukin-6.
In this study, Professor Kim and his team observed that a repebody consists of repeated modules, and they conceived a module-based affinity amplification technology that can effectively increase the binding affinity with the disease target. The developed therapeutic candidate has been confirmed in cell and animal experiments to show low immunogenicity, as well as to strongly inhibit the proliferation of non-small-cell lung cancer.
Furthermore, by investigating the complex structure of the repebody with interleukin-6, Professor Kim has identified its mechanism, which demonstrated the potential for therapeutic development. The researchers are currently carrying out pre-clinical trials for acquiring permission to perform clinical trials on animals with non-small-cell lung cancer. The repebody can be developed into a new protein drug after demonstrating its safety and efficacy.
Professor Hak-Sung Kim and his team have confirmed that the repebody can be utilized as a new protein drug, and this will be a significant contribution to Korea’s protein drugs and biotechnology industry development.
The research was supported by the Future Pioneer Industry project and sponsored by the Ministry of Science, ICT and Future Planning.
Figure 1. Professor Kim’s article published as the cover article of July edition of Molecular Therapy
Figure 2. Clinical proof of the repebody’s inhibition of cancer growth using animal models
2014.07.14 View 12121 -
The First Demonstration of a Self-powered Cardiac Pacemaker
As the number of pacemakers implanted each year reaches into the millions worldwide, improving the lifespan of pacemaker batteries has been of great concern for developers and manufacturers. Currently, pacemaker batteries last seven years on average, requiring frequent replacements, which may pose patients to a potential risk involved in medical procedures.
A research team from the Korea Advanced Institute of Science and Technology (KAIST), headed by Professor Keon Jae Lee of the Department of Materials Science and Engineering at KAIST and Professor Boyoung Joung, M.D. of the Division of Cardiology at Severance Hospital of Yonsei University, has developed a self-powered artificial cardiac pacemaker that is operated semi-permanently by a flexible piezoelectric nanogenerator.
The artificial cardiac pacemaker is widely acknowledged as medical equipment that is integrated into the human body to regulate the heartbeats through electrical stimulation to contract the cardiac muscles of people who suffer from arrhythmia. However, repeated surgeries to replace pacemaker batteries have exposed elderly patients to health risks such as infections or severe bleeding during operations.
The team’s newly designed flexible piezoelectric nanogenerator directly stimulated a living rat’s heart using electrical energy converted from the small body movements of the rat. This technology could facilitate the use of self-powered flexible energy harvesters, not only prolonging the lifetime of cardiac pacemakers but also realizing real-time heart monitoring.
The research team fabricated high-performance flexible nanogenerators utilizing a bulk single-crystal PMN-PT thin film (iBULe Photonics). The harvested energy reached up to 8.2 V and 0.22 mA by bending and pushing motions, which were high enough values to directly stimulate the rat’s heart.
Professor Keon Jae Lee said:
“For clinical purposes, the current achievement will benefit the development of self-powered cardiac pacemakers as well as prevent heart attacks via the real-time diagnosis of heart arrhythmia. In addition, the flexible piezoelectric nanogenerator could also be utilized as an electrical source for various implantable medical devices.”
This research result was described in the April online issue of Advanced Materials (“Self-Powered Cardiac Pacemaker Enabled by Flexible Single Crystalline PMN-PT Piezoelectric Energy Harvester”: http://onlinelibrary.wiley.com/doi/10.1002/adma.201400562/abstract).
Youtube link: http://www.youtube.com/watch?v=ZWYT2cU_Mog&feature=youtu.be
Picture Caption: A self-powered cardiac pacemaker is enabled by a flexible piezoelectric energy harvester.
2014.06.25 View 15763 -
2014 Conference on Korean Sociology Held at KAIST
The Korean Sociological Association (KSA) hosted a two-day conference in 2014 entitled “In the age of anxiety, sociology can present answers” at the College of Liberal Arts and Convergence Science, KAIST, on June 20-21, 2014. Professor Jung-Ro Yoon of the Department of Humanities and Social Sciences at KAIST is the President of KSA. The conference addressed issues such as big data and risk society. During the conference, 40 sessions took place, and 150 research papers were released.
Professor Yoon said, “The conference will offer a great opportunity for Korean sociologists to discuss anxiety, chaos, risk, and the uncertainty that Korean society experiences and suggest answers and a new vision upon which Korean society should move forward.”
2014.06.22 View 7487 -
Professor Won Do Heo on LED Light Technology for Controlling Proteins in Living Cells
With the newly developed LED technology, Professor Won Do Heo at the College of Life Science and Bioengineering, KAIST, was able to suppress cell migration and division when cells are exposed to LED light. This suggests a breakthrough to apply in future cancer cell research.
Professor Heo talked about the impact of his research in the following excerpt from a news article:
“We are already conducting research on the spread of cancer, as well as brain science in animal models with the Light-Activated Reversible Inhibition by Assembled Trap. I believe this technology will be a breakthrough in investigating cancer treatments and the function of neurons in a complex neural network, which existing technologies have not been able to do.”
From EE Times Europe, June 19, 2014
“LED Light Technology Controls Proteins in Living Cells”
http://www.ledlighting-eetimes.com/en/led-light-technology-controls-proteins-in-living-cells.html?cmp_id=7&news_id=222909336
2014.06.22 View 7559 -
First Instance of Negative Effects from Terahertz-Range Electromagnetic Waves
Professor Philhan Kim
Electromagnetic waves (EM-wave) in the terahertz range were widely regarded as the “dream wavelength” due to its perceived neutrality. Its application was also wider than X-rays. However, KAIST scientists have discovered negative effects from terahertz EM-waves.
Professor Philhan Kim of KAIST’s Graduate School of Nanoscience and Technology and Dr. Young-wook Jeong of the Korea Atomic Energy Research Institute (KAERI) observed inflammation of animal skin tissue when exposed to terahertz EM-waves.
The results were published in the online edition of Optics Express (May 19, 20104).
Terahertz waves range from 0.1 to 10 terahertz and have a longer wavelength than visible or infrared light. Commonly used to see through objects like the X-ray, it was believed that the low energy of terahertz waves did not inflict any harm on the human body.
Despite being applied for security checks, next-generation wireless communications, and medical imaging technology, little research has been conducted in proving its safety and impact. Conventional research failed to predict the exact impact of terahertz waves on organic tissues as only artificially cultured cells were used.
The research team at KAERI developed a high power terahertz EM-wave generator that can be used on live organisms. A high power generator was necessary in applications such as biosensors and required up to 10 times greater power than currently used telecommunications EM-wave. Simultaneously, a KAIST research team developed a high speed, high resolution video-laser microscope that can distinguish cells within the organism.
The experiment exposed 30 minutes of terahertz EM-wave on genetically modified mice and found six times the normal number of inflammation cells in the skin tissue after six hours. It was the first instance where negative side effects of terahertz EM-wave were observed.
Professor Kim commented that “the research has set a standard for how we can use the terahertz EM-wave safely” and that “we will use this research to analyze and understand the effects of other EM-waves on organisms.”
2014.06.20 View 8799 -
KAIST Made Great Improvements of Nanogenerator Power Efficiency
The energy efficiency of a piezoelectric nanogenerator developed by KAIST has increased by almost 40 times, one step closer toward the commercialization of flexible energy harvesters that can supply power infinitely to wearable, implantable electronic devices.
NANOGENERATORS are innovative self-powered energy harvesters that convert kinetic energy created from vibrational and mechanical sources into electrical power, removing the need of external circuits or batteries for electronic devices. This innovation is vital in realizing sustainable energy generation in isolated, inaccessible, or indoor environments and even in the human body.
Nanogenerators, a flexible and lightweight energy harvester on a plastic substrate, can scavenge energy from the extremely tiny movements of natural resources and human body such as wind, water flow, heartbeats, and diaphragm and respiration activities to generate electrical signals. The generators are not only self-powered, flexible devices but also can provide permanent power sources to implantable biomedical devices, including cardiac pacemakers and deep brain stimulators.
However, poor energy efficiency and a complex fabrication process have posed challenges to the commercialization of nanogenerators. Keon Jae Lee, Associate Professor of Materials Science and Engineering at KAIST, and his colleagues have recently proposed a solution by developing a robust technique to transfer a high-quality piezoelectric thin film from bulk sapphire substrates to plastic substrates using laser lift-off (LLO).
Applying the inorganic-based laser lift-off (LLO) process, the research team produced a large-area PZT thin film nanogenerators on flexible substrates (2cm x 2cm).
“We were able to convert a high-output performance of ~250 V from the slight mechanical deformation of a single thin plastic substrate. Such output power is just enough to turn on 100 LED lights,” Keon Jae Lee explained.
The self-powered nanogenerators can also work with finger and foot motions. For example, under the irregular and slight bending motions of a human finger, the measured current signals had a high electric power of ~8.7 μA. In addition, the piezoelectric nanogenerator has world-record power conversion efficiency, almost 40 times higher than previously reported similar research results, solving the drawbacks related to the fabrication complexity and low energy efficiency.
Lee further commented,
“Building on this concept, it is highly expected that tiny mechanical motions, including human body movements of muscle contraction and relaxation, can be readily converted into electrical energy and, furthermore, acted as eternal power sources.”
The research team is currently studying a method to build three-dimensional stacking of flexible piezoelectric thin films to enhance output power, as well as conducting a clinical experiment with a flexible nanogenerator.
This research result, entitled “Highly-efficient, Flexible Piezoelectric PZT Thin Film Nanogenerator on Plastic Substrates,” was published as the cover article of the April issue of Advanced Materials. (http://onlinelibrary.wiley.com/doi/10.1002/adma.201305659/abstract)
YouTube Link: http://www.youtube.com/watch?v=G_Fny7Xb9ig
Over 100 LEDs operated by self-powered flexible piezoelectric thin film nanogenerator
Flexible PZT thin film nanogenerator using inorganic-based laser lift-off process
Photograph of large-area PZT thin film nanogenerator (3.5cm × 3.5cm) on a curved glass tube and 105 commercial LEDs operated by self-powered flexible piezoelectric energy harvester
2014.05.19 View 13610 -
Immune Evasion Mechanism of Hepatitis C Virus Revealed
Professor Ui-Cheol Shin
Inhibiting major histocompatibility complex [MHC] class I protein expression, T cell immune response is evaded.
The research will be a great help to the development of C hepatitis vaccine.
Roughly 1-2% of the population in Korea is known to be infected with Hepatitis C. Most Hepatitis C Virus (HCV) infections progress to a chronic disease and can cause liver cirrhosis or liver cancer, which may lead to death.
Unlike Hepatitis type A or B, there is no vaccine for Hepatitis C Virus and therefore avoiding exposure to the virus is the best known method of prevention. However, a team of researchers at KAIST has produced research results, which may contribute significantly to the vaccine development.
KAIST Graduate School of Medical Sciences & Engineering’ Professor Ui-Cheol Shin and his team have successfully identified why Hepatitis C Virus does not cause an immune response within the human body. The research results were published in the May edition of The Journal of Gastroenterology, a world-renowned journal in the field of gastroenterology.
The immune response occurs to eliminate the virus that has invaded our body. During this process, a major histocompatibility complex [MHC] class I plays a key role in inducing T cell response, which is needed for the elimination of virus-infected cells.
When a cell is infected by a virus, a substance called interferon causes the increased expression of major histocompatibility complex class I. T cell recognizes the increased MHC class I and therefore finds the virus-infected cells.
However, the effect that Hepatitis C Virus has on major histocompatibility complex class I has not been clearly identified until now.
The research team has revealed, using a cell culture for infection systems, that the Hepatitis C Virus suppresses the expression of major histocompatibility complex class I. Also, the mechanism to prove that HCV activates a protein called PKR within the cell to inhibit MHC class I protein expression was identified at a molecular level.
In this study, researchers established the hypothesis that regulating PKR protein in the cell can enhance the T cell immune response, which was then proved through experiments.
Professor Ui-Cheol Shin said, “There are a lot of new drugs to treat Hepatitis C Virus, while its vaccine has not been developed yet. Revealing the HCV immune evasion mechanism will help stimulate momentum for the HCV vaccine development.”
The first author of the journal, Dr. Won-Seok Kang is a graduate from Yonsei College of Medicine. After earning his medical degree, he has continued his training as a ‘doctor-scientist’ at KAIST Graduate School of Medical Sciences & Engineering to study Hepatitis C Virus immune evasion mechanism in this research.
Hepatitis C Virus activates PKR-eIF2a pathway, which inhibits the major histocompatibility complex class I, and therefore weakens the T cell activation to the viral activity.
2014.05.19 View 10459 -
Binding Regulatory Mechanism of Protein Biomolecules Revealed
Professor Hak-Sung Kim
A research team led by Professor Hak-Sung Kim of Biological Sciences, KAIST, and Dr. Mun-Hyeong Seo, KAIST, has revealed a regulatory mechanism that controls the binding affinity of protein’s biomolecules, which is crucial for the protein to recognize molecules and carry out functions within the body.
The research results were published in the April 24th online edition of Nature Communications.
The protein, represented by enzyme, antibody, or hormones, specifically recognizes a variety of biomolecules in all organisms and implements signaling or immune response to precisely adjust and maintain important biological processes. The protein binding affinity of biomolecules plays a crucial role in determining the duration of the bond between two molecules, and hence to determine and control the in-vivo function of proteins.
The researchers have noted that, during the process of proteins’ recognizing biomolecules, the protein binding affinity of biomolecules is closely linked not only to the size of non-covalent interaction between two molecules, but also to the unique kinetic properties of proteins.
To identify the basic mechanism that determines the protein binding affinity of biomolecules, Professor Kim and his research team have made mutation in the allosteric site of protein to create a variety of mutant proteins with the same chemical binding surface, but with the binding affinity vastly differing from 10 to 100 times. The allosteric site of the protein refers to a region which does not directly bind with biomolecules, but crucially influences the biomolecule recognition site.
Using real-time analysis at the single-molecule level of unique kinetic properties of the produced mutant proteins, the researchers were able to identify that the protein binding affinity of biomolecules is directly associated with the protein’s specific kinetic characteristics, its structure opening rate.
Also, by proving that unique characteristics of the protein can be changed at the allosteric site, instead of protein’s direct binding site with biomolecules, the researchers have demonstrated a new methodology of regulating the in-vivo function of proteins.
The researchers expect that these results will contribute greatly to a deeper understanding of protein’s nature that governs various life phenomena and help evaluate the proof of interpreting protein binding affinity of biomolecules from the perspective of protein kinetics.
Professor Kim said, “Until now, the protein binding affinity of biomolecules was determined by a direct interaction between two molecules. Our research has identified an important fact that the structure opening rate of proteins also plays a crucial role in determining their binding affinity.”
[Picture]
A correlation graph of opening rate (kopening) and binding affinity (kd) between protein’s stable, open state and its unstable, partially closed state.
2014.05.02 View 9346 -
An Electron Cloud Distribution Observed by the Scanning Seebeck Microscope
All matters are made of small particles, namely atoms. An atom is composed of a heavy nucleus and cloud-like, extremely light electrons.
Korean researchers developed an electron microscopy technique that enables the accurate observation of an electron cloud distribution at room-temperature. The achievement is comparable to the invention of the quantum tunneling microscopy technique developed 33 years ago.
Professor Yong-Hyun Kim of the Graduate School of Nanoscience and Technology at KAIST and Dr. Ho-Gi Yeo of the Korea Research Institute of Standards and Science (KRISS) developed the Scanning Seebeck Microscope (SSM). The SSM renders clear images of atoms, as well as an electron cloud distribution. This was achieved by creating a voltage difference via a temperature gradient.
The development was introduced in the online edition of Physical Review Letters (April 2014), a prestigious journal published by the American Institute of Physics.
The SSM is expected to be economically competitive as it gives high resolution images at an atomic scale even for graphene and semiconductors, both at room temperature. In addition, if the SSM is applied to thermoelectric material research, it will contribute to the development of high-efficiency thermoelectric materials.
Through numerous hypotheses and experiments, scientists now believe that there exists an electron cloud surrounding a nucleus. IBM's Scanning Tunneling Microscope (STM) was the first to observe the electron cloud and has remained as the only technique to this day. The developers of IBM microscope, Dr. Gerd Binnig and Dr. Heinrich Rohrer, were awarded the 1986 Nobel Prize in Physics.
There still remains a downside to the STM technique, however: it required high precision and extreme low temperature and vibration. The application of voltage also affects the electron cloud, resulting in a distorted image.
The KAIST research team adopted a different approach by using the Seebeck effect which refers to the voltage generation due to a temperature gradient between two materials.
The team placed an observation sample (graphene) at room temperature (37~57℃) and detected its voltage generation. This technique made it possible to observe an electron cloud at room temperature.
Furthermore, the research team investigated the theoretical quantum mechanics behind the electron cloud using the observation gained through the Seebeck effect and also obtained by simulation capability to analyze the experimental results.
The research was a joint research project between KAIST Professor Yong-Hyun Kim and KRISS researcher Dr. Ho-Gi Yeo. Eui-Seop Lee, a Ph.D. candidate of KAIST, and KRISS researcher Dr. Sang-Hui Cho also participated. The Ministry of Science, ICT, and Future Planning, the Global Frontier Initiative, and the Disruptive Convergent Technology Development Initiative funded the project in Korea.
Picture 1: Schematic Diagram of the Scanning Seebeck Microscope (SSM)
Picture 2: Electron cloud distribution observed by SSM at room temperature
Picture 3: Professor Yong-Hyun Kim
2014.04.04 View 12981 -
Extreme Tech: Nanowire "impossible to replicate" fingerprints could eliminate fraud, counterfeit goods
Research done by Professor Hyun-Joon Song of Chemistry at KAIST on
anti-counterfeit, nanoscale fingerprints generated by randomly distributed
nanowires was introduced by Extreme Tech, an online global science and technology
news.
For the articles, please go to:
Extreme Tech, March 25, 2014Nanowire ‘impossible to replicate’ fingerprints could eliminate fraud, counterfeit goods
http://www.extremetech.com/extreme/179131-nanowire-impossible-to-replicate-fingerprints-could-eliminate-fraud-counterfeit-goods
2014.03.26 View 7812 -
KAIST Holds Open Lecture For Daejeon Residents
Free of cost for any Korean citizen, the registration for the new course opens on the official website from 5th March KAIST’s Department of Humanities and Social Science is currently operating free humanities and liberal arts classes for Daejeon residents.
The theme of the course for this semester is “World and Politics,” which will begin on 13th March and run every Thursday for 6 weeks at KAIST’s International Seminar Room.
This course has been organized to introduce the general public to the current political situation with neighboring countries such as China, Japan and North Korea, as well as the characteristics of multinational companies.
Top experts in the related fields will give lectures. First, Professor Ha-Yong Jung from Kyunghee University will talk on “American liberalism and democracy”; Professor Gyeong-Mo An from Korea National Defense University on “Kim Jeong-Eun and the Future of North Korea--Is the Collapse of North Korea A Reality?” and Ja-Seon Koo, a visiting professor at Korea National Diplomatic Academy on “The Chinese Communist Party during the Xi Jinping Period.”
“With the era of globalization, the political situations in the neighboring countries have both direct and indirect effects on our lives,” said Professor Hyeon-Seok Park who has organized the courses. "These classes will be an opportunity for our citizens to understand and learn about the current affairs in the world.”
Anyone can attend the course, and registration is from March 5th to 9th at the official webpage of KAIST’s Humanities and Social Sciences Department (http://hss.kaist.ac.kr). All the courses are free of charge.
Contact: Department of Humanities and Social Science Research (Tel. 350-4687, E-mail: baobab@kaist.ac.kr)
2014.03.06 View 6411