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A mechanism for how reactive oxygen species cause cell responses studied
A research team led by Professor Kwang-Hyun Cho of the Department of Biology and Brain Engineering, KAIST, and Dr. Gi-Sun Kwon of the Korea Research Institute of Bioscience and Biotechnology succeeded in proving the mechanism behind the determination of cell life in relation to reactive oxygen species.
The results of the venture were published in the June 3rd edition of Science Signaling. The title of the research paper is “MLK3 is part of a feedback mechanism that regulates different cellular responses to reactive oxygen species.”
The research team discovered that the molecular switch that determines the division of apoptosis of a cell was based on MLK3 feedback mechanism. MLK stands for mixed-lineage kinase.
Under sufficient stress, the mechanism instructs the cell to undergo the division but in an overly stressful environment, the mechanism stops the cell division and instead, induces apoptosis. This discovery is expected to be a breakthrough in illnesses related to the concentration of the reactive oxygen species (ROS).
At low concentration of ROS, the protein associated with cell division, ERK (extracellular-signal-regulated kinase), is activated while as the ROS concentration increases, JNK (c-Jun N-terminal protein kinases), responsible for apoptosis, becomes activated. Furthermore, through computer simulation analysis and mathematical modeling, in tandem with molecular cell biology experiments, the MLK3 based feedback mechanism was the fundamental molecular switch that determines the balance between ERK and JNK, and ultimately the cell’s responses.
Professor Cho commented that “the contradicting cell responses to ROS had remained a mystery, but with the system biology, an approach in which information technology and biotechnology converge, such riddles can be resolved. We expect that the proven mechanism will be used to overcome aging or cancer growth as a result of ROS in the near future.”
Picture shows the process of identifying cell responses caused by reactive oxygen species.
2014.06.13 View 8781 -
A Molecular Switch Controlling Self-Assembly of Protein Nanotubes Discovered
International collaborative research among South Korea, United States, and Israel research institutionsThe key to the treatment of cancer and brain disease mechanism The molecular switch that controls the self-assembly structure of the protein nanotubes, which plays crucial role in cell division and intracellular transport of materials, has been discovered. KAIST Bio and Brain Engineering Department’s Professor Myeong-Cheol Choi and Professor Chae-Yeon Song conducted the research, in collaboration with the University of California in Santa Barbara, U.S., and Hebrew University in Israel. The findings of the research were published in Nature Materials on the 19th. Microtubules are tube shaped and composed of protein that plays a key role in cell division, cytoskeleton, and intercellular material transport and is only 25nm in diameter (1/100,000 thickness of a human hair). Conventionally, cancer treatment focused on disrupting the formation of microtubules to suppress the division of cancer cells. In addition Alzheimer’s is known to be caused by the diminishing of structural integrity of microtubules responsible for intercellular material transport which leads to failure in signal transfer. The research team utilized synchrotron x-ray scattering and transmission electron microscope to analyze the self assemble structure of protein nanotubes to subnanometer accuracy. As a result, the microtubules were found to assemble into 25nm thickness tubules by stacking protein blocks 4 x 5 x 8nm in dimension. In the process, the research team discovered the molecular switch that controls the shape of these protein blocks. In addition the research team was successful in creating a new protein tube structure. Professor Choi commented that they were successful in introducing a new paradigm that suggests the possibility of controlling the complex biological functions of human’s biological system with the simple use of physical principles. He commented further that it is anticipated that the findings will allow for the application of bio nanotubes in engineering and that this is a small step in finding the mechanism behind cancer treatment and neural diseases.
2014.02.03 View 9790 -
Space Observatory Video by Science & Technology Satellite No. 3 Released
Images of the Andromeda Galaxy, the Orion Nebula, and the Rosetta Nebula taken by the Science & Technology Satellite No. 3, which was built by the KAIST Satellite Technology Research Center and launched at the Yasny launch site in Russia, were released on December 17, 21 st and 22 nd , 2013.
The Andromeda Galaxy (M31) is the nearest spiral galaxy and is located about two million light years away from the earth. The first image received was an infrared image recorded by the space telescope loaded in the satellite.
Research using the satellite’s infrared camera and imaging spectrometer for observing the Earth will also be conducted until February, 2014. After that, the satellite will be collecting images on infrared cosmic background radiation and exploring the galactic plane at a height of 600 km for two years. The infrared and spectrometer images from the Earth observation can be utilized for disaster monitoring and applied to basic research for the detection of wildfires and urban heat island effect as well as flood damage observation and water quality prediction.
Infrared Light Observed in the Universe, Andromeda Galaxy
2014.01.13 View 7988 -
Opening Ceremony of Genetic Donguibogam held
- Medicine using traditional natural substances • Food product source technology development begins
- Over 150,000,000,000 Won for 10 years of work invested to develop source technology
- Opening ceremony held on November 26th at 3 p.m. in Bio & Brain Engineering Division Building
The research to develop medicine and food source technology using traditional natural substances hasbegun.The opening ceremony of the “Genetic Donguibogam” business group, with KAIST Department of Bio & Brain Engineering Professor Do Heon Lee as the leader, was held on November 26th at 3 p.m. in Dream Hall, Bio & Brain Engineering Division Building, KAIST, Daejeon. The attendees of the opening ceremony included Yo Eop Im, Head of the Future Technology Department of the Ministry of Science, ICT and Future Planning and around 200 experts in science and technology industry, including the National Research Foundation of Korea, KAIST, the Korea Institute of Science and Technology, Seoul National University and Yonsei University.
The business group was established to re-interpret traditional natural substances proved to be effective from experience and improve quality of life by researching its applications; and to develop integrated source technology using traditional natural substances. The group is to invest over 150,000,000,000 Won for 10 years of research to secure natural substance source technology in five stages: interpretation technology, analysis technology, verification technology, bio marker technology and human body effectiveness verification technology. Especially, the focus would be on the use of virtual body computer models and Omics* to analyse the effects of traditional natural substances mixture on human body, and to find new materials for healthcare.
This research model, it is hoped, will have a new item to pioneer in the world natural substance market as well as securing a technologically competitive edge in bio industry by developing source technology that investigates the effects of traditional natural substances using cutting edge science.
KAIST Department of Bio & Brain Engineering Professor and Head Do Heon Lee of the “Genetic Donguibogam” Business Group said, “We will push forward to develop source energy by integrating IT-BT technology with a computer virtual body to build a cooperation system with medicine and functional food industries.” He continued: “This will enable not only the creation of a new industry, but also customised medicine.”
The 12 partners of the group include KAIST, Korea Institute of Science and Technology, Seoul National University and Yonsei University and 200 experts. The research participation area will be widened to foreign research institutes and associated companies.
* Terminology
Noun) Omics is an academic discipline analysing mass information on metabolism of physiological phenomena in specific cells (transcriptome, proteome and protoplast) with an integrated approach to determine vital phenomena.
2013.12.11 View 8500 -
Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness
Professor Christopher D. Fiorillo of the Bio & Brain Engineering (http://ineuron.kaist.ac.kr/web/home.html) at KAIST published a research paper in the August 2 issue of Science. The title of the paper is “Two Dimensions of Value: Dopamine Neurons Represent Reward but not Aversiveness.” The following is an introduction of his research work:
To make decisions, we need to estimate the value of sensory stimuli and motor actions, their “goodness” and “badness.” We can imagine that good and bad are two ends of a single continuum, or dimension, of value. This would be analogous to the single dimension of light intensity, which ranges from dark on one end to bright light on the other, with many shades of gray in between. Past models of behavior and learning have been based on a single continuum of value, and it has been proposed that a particular group of neurons (brain cells) that use dopamine as a neurotransmitter (chemical messenger) represent the single dimension of value, signaling both good and bad.
The experiments reported here show that dopamine neurons are sensitive to the value of reward but not punishment (like the aversiveness of a bitter taste). This demonstrates that reward and aversiveness are represented as two discrete dimensions (or categories) in the brain. “Reward” refers to the category of good things (food, water, sex, money, etc.), and “punishment” to the category of bad things (stimuli associated with harm to the body and that cause pain or other unpleasant sensations or emotions).
Rather than having one neurotransmitter (dopamine) to represent a single dimension of value, the present results imply the existence of four neurotransmitters to represent two dimensions of value. Dopamine signals evidence for reward (“gains”) and some other neurotransmitter presumably signals evidence against reward (“losses”). Likewise, there should be a neurotransmitter for evidence of danger and another for evidence of safety. It is interesting that there are three other neurotransmitters that are analogous to dopamine in many respects (serotonin, norepinephrine, and acetylcholine), and it is possible that they could represent the other three value signals.
For the research article, please visit: http://www.sciencemag.org/content/341/6145/546.abstract
For the Science 2nd issue, please visit: http://www.sciencemag.org/content/current#ResearchArticles
Illustration of Value Dimension
2013.08.08 View 7488 -
KAIST Alumni Association Selects 'Proud Alums'
KAIST Alumni Association selected ‘Proud Alums’ who have contributed to the development of Korea and society and brought honor to KAIST.
The Alums selected were: CEO of Hyundai Heavy Industry Lee Jae Seong, Vice President of SK Hynix Park Sang Hoon, President of Samsung Display Kim Ki Nam, Director of Korea Research Institute of Standards and Science Kang Dae Lim, and President of Dawonsys Park Sun Soon.
Lee Jae Song (Department of Industrial and Systems Engineering, M.S. 3rd) has led Hyundai Heavy Industries through innovation and had contributed in the development of Korea and oversaw the growth of Hyundai Heavy Industries to number 1 in Shipbuilding.
Park Sang Hoon (Biological and Chemical Engineering, M.S. 5th) has led SK Hynix in the fields of energy, chemical and biological medicine and oversaw the development of world class R&D and production technologies to aid the development of Korea.
Kim Ki Nam (Electrical and Electronic Engineering, M.S. 9th) has led the development of innovative semiconductor technologies thereby helping strengthening the competitiveness of Korean semiconductor industry.
Kang Dae Lim (Mechanical Engineering, Ph.D. 1994 graduate) has helped in the development of Korean science and technology by leading the field of measurement standardization as Chairman of International Measurement Confederation and Chairman of Korea Association of Standards & Testing Organizations.
Park Sun Soon (Electrical and Electronic Engineering, M.S. 12th) has succeeded in advancing the field of electronics by pioneering the field of creative technology.
2013.01.22 View 8828
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Firefly inspired high efficiency LED technology developed
A firefly inspired, high efficiency self-illuminating LED has been developed.
Professor Jeong Gi Hoon (Department of Bio and Brain Engineering) mimicked the nanostructure of the external layer of the illumination organ of a firefly and succeeded in fabricating high illumination efficiency LED lenses.
Conventional lenses required expensive anti-reflection coating. The developed lenses utilize the bio-inspired nanostructure on the surface of the lenses themselves to reduce the reflectivity of the lenses thereby decreasing production costs.
The developed antireflection nanostructure is expected to be applied to various digital devices and lighting fixtures.
Antireflective structures have been applied in various fields in order to enhance light efficiency However these structures have been limited to flat surfaces and therefore was difficult to implement to curved surfaces like LED lenses.
Professor Jeong’s team solved this problem by using three dimensional micro molding processes.
The team fabricated the nanostructure by forming a single nanoparticle layer on the silicon oxide and performing dry etching. On this nanostructure PDMS was poured and manipulated to fabricate a lens structure similar to that of a firefly.
The fabricated lens showed similar efficiency as conventional antireflection coating.
2012.11.29 View 7879
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KAIST and JAIT Sign MOU
KAIST and JAIT (Jeonbuk Institute of Automotive Technology) signed a MOU for the training and development of future automobile technology.
JAIT is the domestic front runner in automobile research and the MOU will allow KAIST to participate with JAIT on research and development of automobile technology.
Research on future vehicle technology, transportation system using electric transport system, cooperation in education, research and development, and international business, and knowledge transfer are all part of the MOU.
2012.11.29 View 6804
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Liver Damage Mechanism of Hepatitis C Proven
KAIST researchers found mechanics behind a Hepatitis C virus, thereby taking a step closer to the development of a cure for Hepatitis C.
Professor Choi Chul Hui (Department of Biological and Brain Engineering) and Professor Shin Eui Chul (Graduate School of Medical Sciences) proved, for the first time in the world, the mechanism behind liver damage of a patient with Hepatitis C.
It is anticipated that this discovery will allow for the development of a Hepatitis C cure that has no side effects and little Liver damage.
Hepatitis C is an immune response of the body to the Hepatitis C virus and causes liver irritation.
Around 170million people are infected with Hepatitis C worldwide including 1% of the Korean population. Once infected, most cases turn into chronic cases and may lead to liver cancer.
However it was impossible to infect Hepatitis C within a test tube cell environment until 2005 and up till then Chimpanzees were used to study the virus which proved to be a huge barrier to research.
The research team used cells infected with Hepatitis C virus and found out that the virus works by increasing the destruction of cells by the TNF-a protein responsible for the cell’s immune response.
In addition the protein structure of the virus that causes this reaction was successfully found.
Conventionally the Hepatitis C medication focused on the suppressing the growth of the virus and therefore had many side effects.
The experimental results allow new medication aimed at suppressing the actual mechanism of liver damage to be discovered.
The result was selected as the cover dissertation of the September Edition of the Hepatolog magazine.
2012.09.11 View 11483
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Systems biology demystifies the resistance mechanism of targeted cancer medication
Korean researchers have found the fundamental resistance mechanism of the MEK inhibitor, a recently highlighted chemotherapy method, laying the foundation for future research on overcoming cancer drug resistance and improving cancer survival rates. This research is meaningful because it was conducted through systems biology, a fusion of IT and biotechnology.
The research was conducted by Professor Gwang hyun Cho’s team from the Department of Biology at KAIST and was supported by the Ministry of Education, Science and Technology and the National Research Foundation of Korea.
The research was published as the cover paper for the June edition of the Journal of Molecular Cell Biology (Title: The cross regulation between ERK and PI3K signaling pathways determines the tumoricidal efficacy of MEK inhibitor).
Targeted anticancer medication targets certain molecules in the signaling pathway of the tumor cell and not only has fewer side effects than pre-existing anticancer medication, but also has high clinical efficacy. The technology also allows the creation of personalized medication and has been widely praised by scientists worldwide.
However, resistances to the targeted medication have often been found before or during the clinical stage, eventually causing the medications to fail to reach the drug development stage. Moreover, even if the drug is effective, the survival rate is low and the redevelopment rate is high.
An active pathway in most tumor cells is the ERK (Extracellular signal-regulated kinases) signaling pathway. This pathway is especially important in the development of skin cancer or thyroid cancer, which are developed by the mutation of the BRAF gene inside the path. In these cases, the MEK (Extracellular signal-regulated kinases) inhibitor is an effective treatment because it targets the pathway itself. However, the built-up resistance to the inhibitor commonly leads to the redevelopment of cancer.
Professor Cho’s research team used large scale computer simulations to analyze the fundamental resistance mechanism of the MEK inhibitor and used molecular cell biological experiments as well as bio-imaging* techniques to verify the results.
* Bio-imaging: Checking biological phenomena at the cellular and molecular levels using imagery
The research team used different mutational variables, which revealed that the use of the MEK inhibitor reduced the transmission of the ERK signal but led to the activation of another signaling pathway (the PI3K signaling pathway), reducing the effectiveness of the medication. Professor Cho’s team also found that this response originated from the complex interaction between the signaling matter as well as the feedback network structure, suggesting that the mix of the MEK inhibitor with other drugs could improve the effects of the targeted anticancer medication.
Professor Cho stated that this research was the first of its kind to examine the drug resistivity against the MEK inhibitor at the systematic dimension and showed how the effects of drugs on the signaling pathways of cells could be predicted using computer simulation. It also showed how basic research on signaling networks can be applied to clinical drug use, successfully suggesting a new research platform on overcoming resistance to targeting medication using its fundamental mechanism.
2012.07.06 View 10496
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The output of terahertz waves enhanced by KAIST team
KAIST researchers have greatly improved the output of terahertz waves, the blue ocean of the optics world. This technology is expected to be applied to portable X-ray cameras, small bio-diagnostic systems, and in many other devices.
Professor Ki-Hun Jeong"s research team from the Department of Bio and Brain Engineering used optical nano-antenna technology to increase the output of terahertz waves by three times.
Terahertz waves are electromagnetic waves with frequencies between 100GHz to 30THz. They are produced when a femtosecond (10^-15 s) pulse laser is shone on a semiconductor substrate with photoconduction antennas, causing a photocurrent pulse of one picosecond (10^-12 s). Their long wavelengths, in comparison to visible light and infrared rays, give terahertz waves a high penetration power with less energy than X-rays, making them less harmful to humans.
These qualities allow us to see through objects, just as X-rays do, but because terahertz waves absorb certain frequencies, we can detect hidden explosives or drugs, which was not possible with X-rays. We can even identify fake drugs. Furthermore, using the spectral information, we can analyze a material"s innate qualities without chemical processing, making it possible to identify skin diseases without harming the body. However, the output was not sufficient to be used in biosensors and other applications.
Prof. Jeong"s team added optical nano-antennas, made from gold nano-rods, in between the photoconduction antennas and optimized the structure. This resulted in nanoplasmonic resonance in the photoconduction substrate, increasing the degree of integration of the photocurrent pulse and resulting in a three times larger output.
Hence, it is not only possible to see through objects more clearly, but it is also possible to analyze components without a biopsy.
Professor Jeong explained, "This technology, coupled with the miniaturization of terahertz devices, can be applied to endoscopes to detect early epithelial cancer" and that he will focus on creating and commercializing these biosensor systems.
This research was published in the March issue of the international nanotechnology journal ACS Nano and was funded by the Korea Evaluation Institute of Industrial Technology and the National Research Foundation of Korea.
Figure: Mimetic diagram of a THz generator with nano-antennas
2012.04.29 View 11286 -
Seeing Inside Cells with Fiber Optics
Professor Jiho Park’s research team was successful in receiving minute optical signals from inside the cell using optical nano fibers.
Through the invention of this technology, we can now look inside cells in high resolution without the use of equipment such as endoscopes that damage cells. We will be able to study the biological phenomena within cells, and thus cure diseases more effectively.
Recently, ultra high resolution microscopes have been used to analyze incubated cells. However, because of the need for a very complex and large system, it had been impossible to monitor cells in the less transparent areas of the body in real time.
The research team created the wire with a semiconductor created with tin oxides to be only 100 nanometers in diameter (1nanometer= 1/1billion meters).
The nanowire is connected to the end of the optical fiber, and the light that comes through the optical fiber is transmitted to particular spots in the cell, and the optical signals from the cell are retrieved back from the cell as well
Together with this, based on the fact that nanowires do not damage cells, the research team covered the end of the wire with a photo reactive material and entered this into the cell. They were able to check that the material reacted to light and entered the cell when they transmitted light
Accordingly, this showed the possibilities of the use of this technology as a method of treatment to effectively transfer the medication into the cells.
Prof. Jiho Park stated that “in this research, we only used cells incubated outside the human body, but soon we will use this technology to stimulate and control cells within the body in a minute scale” as well as that “soon, we will be able to study the biological phenomena inside a cell to study diseases and apply this to cure them more effectively”.
This research result has been published in the online publication of ‘Nature Nanotechnology’ on December 18.
This study was done through the cooperation of various schools. Besides Prof. Jiho Park, Prof. Seungman Yang from the Biochemistry department, and Doctor Chuljoon Huh from KAIST, Prof. Yeonho Choi from Biomedical Science department of Korea University, Professor Peidon Yang and Doctor Ruoxue Yan from UC Berkeley’s chemistry department, and Luke Lee from UC Berkeley’s bioengineering department participated in the project.
2012.01.31 View 9101