Science
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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 -
The hereditary factor of autism revealed
Korean researchers have successfully investigated the causes and hereditary factors for autistic behavior and proposed a new treatment method with fewer side effects.
This research was jointly supported by the Ministry of Education, Science and Technology and the National Research Foundation as part of the Leading Researcher and Science Research Center Program
The research findings were publishing in the June edition of Nature magazine and will also be introduced in the July edition of Nature Reviews Drug Discovery, under the title ‘Autistic-like social behavior in Shank2-mutant mice improved by restoring NMDA receptor function’.
The research team found that lack of Shank2 genes in mice, which are responsible for the production of synapse proteins, caused autistic-like behavior. The results strongly suggested that the Shank2 gene was linked to autistic behavior and that Shank2 deficiency induced autistic behaviors.
Autism is a neural development disorder characterized by impaired social interaction, repetitive behavior, mental retardation, anxiety and hyperactivity. Around 100 million people worldwide display symptoms of autistic behavior. Recent studies conducted by the University of Washington revealed that 1 out of 3 young adults who display autistic behavior do not fit into the workplace or get accepted to college, a much higher rate than any other disorder. However, an effective cure has not yet been developed and current treatments are limited to reducing repetitive behavior.
The research team confirmed autistic-like social behavior in mice without the Shank2 genes and that the mice had decreased levels of neurotransmission in the NMDA receptor. The mice also showed damaged synaptic plasticity* in the hippocampus**.
* Plasticity: ability of the connectionbetween two neurons to change in strength in response to transmission of information
**Hippocampus: part of the brain responsible for short-term and long-term memory as well as spatial navigation.
The research team also found out that, to restore the function of the NMDA receptor, the passive stimulation of certain receptors, such as the mGLuR5, yielded better treatment results than the direct stimulation of the NMDA. This greatly reduces the side effects associated with the direct stimulation of receptors, resulting in a more effective treatment method.
This research successfully investigated the function of the Shank2 gene in the nerve tissue and showed how the reduced function of the NMDA receptor, due to the lack of the gene, resulted in autistic behavior. It also provided new possibilities for the treatment of autistic behavior and impaired social interaction
2012.06.24 View 10828
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Flexible Nanogenerator Technology
KAIST research team successfully developed the foundation technology that will enable to fabrication of low cost, large area nanogenerator.
Professor Lee Gun Jae’s team (Department of Materials Science and Engineering) published a dissertation on a nanogenerator using nanocomplexes as the cover dissertation of the June edition of Advanced Materials.
The developed technology is receiving rave reviews for having overcome the complex and size limitations of the nanogenerator fabrication process.
A nanogenerator is an electricity generator that uses materials in the nanoscale and uses piezoelectricity that creates electricity with the application of physical force.
The generation technology using piezoelectricity was appointed as one of top 10 promising technologies by MIT in 2009 and was included in the 45 innovative technologies that will shake the world by Popular Science Magazine in 2010.
The only nanogenerator thus far was the ZnO model suggested by Georgia Tech’s Professor Zhong Lin Wang in 2005.
Professor Lee’s team used ceramic thin film material BaTiO3 which has 15~20 times greater piezoelectric capacity than ZnO and thus improved the overall performance of the device. The use of a nanocomplex allows large scale production and the simplification of the fabrication process itself.
The team created a mixture of PDMS (polydimethylsiloxane) with BaTiO3 and either of CNT (Carbon Nanotube) or RGO (Reduced Graphene Oxide) which has high electrical conductivity and applied this mixture to create a large scale nanogenerator.
2012.06.18 View 12460
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High Capacity Molecular Storage Technology Developed by KAIST Professor Omar M. Yaghi
KAIST research team has succeeded in developing the technology that allows high capacity protein storage.
Professor Omar M. Yaghi (Graduate School of EEWS) and his research team succeeded in developing the core technology that enables the storage of various types of proteins by developing a metal organic structure. The result of their research was published in the May edition of Science magazine.
The newly developed technology can store various types and sizes of proteins. This property is expected to pave way to: 1) development of high capacity, high integration drugs 2) development of virus separation compounds 3) selective removal of protein causing negative reactions in the body 4) permanent preservation of rare polymeric proteins, among other expectations.
In addition it becomes possible to selectively remove and preserve all the body’s cells including stem cells which will aid the development of cures for incurable diseases and increase life expectancy and medical technology in general.
Conventional metal-organic structure used 7 Angstrom large small single molecules and therefore could not be used in the storage of large molecules or proteins. Its usability was proven only as potential high capacity gas storage structure. In addition the internal structure of the metal organic structure is cross linked which made it even more difficult to store large proteins within the structure.
Professor Yaghi’s team used molecular structure over 5nm in length in the development of the metal-organic structure to solve the problem associated with size of structure. The ordered structure of the structure’s pore was observed for the first time using Transmission Electron Microscope.
The new structure enables the ordered storage of large proteins and was able to store vitamin and proteins like myoglobin at high capacity for the first time in the world.
2012.05.30 View 8310
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Production of chemicals without petroleum
Systems metabolic engineering of microorganisms allows efficient production of natural and non-natural chemicals from renewable non-food biomass
In our everyday life, we use gasoline, diesel, plastics, rubbers, and numerous chemicals that are derived from fossil oil through petrochemical refinery processes. However, this is not sustainable due to the limited nature of fossil resources. Furthermore, our world is facing problems associated with climate change and other environmental problems due to the increasing use of fossil resources. One solution to address above problems is the use of renewable non-food biomass for the production of chemicals, fuels and materials through biorefineries. Microorganisms are used as biocatalysts for converting biomass to the products of interest. However, when microorganisms are isolated from nature, their efficiencies of producing our desired chemicals and materials are rather low. Metabolic engineering is thus performed to improve cellular characteristics to desired levels. Over the last decade, much advances have been made in systems biology that allows system-wide characterization of cellular networks, both qualitatively and quantitatively, followed by whole-cell level engineering based on these findings. Furthermore, rapid advances in synthetic biology allow design and synthesis of fine controlled metabolic and gene regulatory circuits. The strategies and methods of systems biology and synthetic biology are rapidly integrated with metabolic engineering, thus resulting in "systems metabolic engineering".
In the paper published online in Nature Chemical Biology on May 17, Professor Sang Yup Lee and his colleagues at the Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea present new general strategies of systems metabolic engineering for developing microorganisms for the production of natural and non-natural chemicals from renewable biomass. They first classified the chemicals to be produced into four categories based on whether they have thus far been identified to exist in nature (natural vs. nonnatural) and whether they can be produced by inherent pathways of microorganisms (inherent, noninherent, or created): natural-inherent, natural-noninherent, non-natural-noninherent, and non-natural-created ones. General strategies for systems metabolic engineering of microorganisms for the production of these chemicals using various tools and methods based on omics, genome-scale metabolic modeling and simulation, evolutionary engineering, synthetic biology are suggested with relevant examples. For the production of non-natural chemicals, strategies for the construction of synthetic metabolic pathways are also suggested. Having collected diverse tools and methods for systems metabolic engineering, authors also suggest how to use them and their possible limitations.
Professor Sang Yup Lee said "It is expected that increasing number of chemicals and materials will be produced through biorefineries. We are now equipped with new strategies for developing microbial strains that can produce our desired products at very high efficiencies, thus allowing cost competitiveness to those produced by petrochemical refineries."
Editor of Nature Chemical Biology, Dr. Catherine Goodman, said "It is exciting to see how quickly science is progressing in this field – ideas that used to be science fiction are taking shape in research labs and biorefineries. The article by Professor Lee and his colleagues not only highlights the most advanced techniques and strategies available, but offers critical advice to progress the field as a whole."
The works of Professor Lee have been supported by the Advanced Biomass Center and Intelligent Synthetic Biology Center of Global Frontier Program from the Korean Ministry of Education, Science and Technology through National Research Foundation.
Contact: Dr. Sang Yup Lee, Distinguished Professor and Dean, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930)
2012.05.23 View 11730
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Biomimetic reflective display technology developed
Professor Shin Jung Hoon
The bright colors of a rainbow or a peacock are produced by the reflection and interference of light in transparent periodic structures, producing what is called a structural color. These colors are very bright and change according to the viewing angle. On the other hand, the wings of a morpho-butterfly also have structural colors but are predominantly blue over a wide range of angles. This is because the unique structure of the morpho-butterfly’s wings contains both order and chaos.
Professor Shin Jung Hoon’s team from the Department of Physics and the Graduate School of Nanoscience and Technology at KAIST produced a display that mimics the structure of the morpho-butterfly’s wings using glass beads.
This research successfully produced a reflective display (one that reflects external light to project images), which could be used to make very bright displays with low energy consumption. This technology can also be used to make anti-counterfeit bills, as well as coating materials for mobile phones and wallets.
The structure of the morpho-butterfly’s wings seems to be in periodic order at the 1-micrometer level, but contains disorder at the 100-nanometer level. So far, no one had succeeded in reproducing a structure with both order and disorder at the nanometer level.
Professor Shin’s team randomly aligned differently sized glass beads of a few hundred nanometers to create chaos and placed a thin periodic film on top of it using the semiconductor deposition method, thereby creating the morpho-butterfly-like structure over a large area.
This new development produced better color and brightness than the morpho-butterfly wing and even exhibited less color change according to angle. The team sealed the film in thin plastic, which helped to maintain the superior properties whilst making it more firm and paper-like.
Professor Shin emphasized that the results were an exemplary success in the field of biomimetics and that structural colors could have other applications in sensors and fashion, for example.
The results were first introduced on May 3rd in Nature as one of the Research Highlights and will be published in the online version of the material science magazine, Advanced Materials.
This research was jointly conducted by Professor Shin Jung Hoon (Department of Physics / Graduate School of Nanoscience and Technology at KAIST), Professor Park NamKyoo (Department of Electrical and Computer Engineering at Seoul National University), and Samsung Advanced Institute of Technology. The funding was provided by the National Research Foundation of Korea and the Ministry of Education, Science and Technology as part of the World Class University (WCU) project.
Figure 2. The biomimetic film can express many different colors
Figure 3. The biomimetic diplay and a morpho-butterfly
2012.05.07 View 13416 -
NPKI Launch Workshop Held
Molecular Physics Department Expected to Have ‘NPKI’ Launch Workshop
- Numerous physicists tracking the god-particle ‘Higgs’ attending-
The NPKI: New Physics at Korea Institute which was launched a six day workshop in Shinla Hotel, Seoul with 50 physicists from in and out of the country.
The event started with Professor Gi Woon Choi’s welcoming speech. A heated debate with the theme ‘Top physics and electroweak symmetry breaking in the LHC era’ took place in the event.
NPKI was created this year to search into the most fundamental workings of nature, research the meaning of such mechanisms, and share this knowledge with not only the general public, but also with the teenagers who wish to someday become physicists.
Professor Gi Woon Choi from KAIST, Professors Byoung Wong Ko and Eung Jin Jeon from the Advanced Science Institute, and more are participated in this workshop from Korea.
From abroad, world renowned professors such as Prof. Csaba Csaki from Cornell, Prof. Christophe Grojean from CERN, Prof. Erez Etzion from Tel Aviv University of Israel, and Prof. Zoltan Ligeti from UC Berkley participated in this event.
The ‘Seeds Program’ took place. This is a program where 20 high school and middle school students aspiring to become physicists were able to attend the work shop without any due fee to experience the world of physicists.
The students chosen for the program were able to attend the conference to watch debates of real physicists as well as experience the academic lives of physicists. They were also able to attend the lecture conducted by Prof. Gilad Perez from CERN and were granted question and answer sessions as well.
The workshop was hosted by NPKI, and sponsored by Shinla Hotel, BK21 KAIST Physics, department of physics of KAIST, department of physics in Seoul National University, the Advanced Science Institute, and the Center for Quantum Spacetime
2012.04.04 View 11893
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Inexpensive Separation Method of Graphene Developed
The problem with commercializing graphene that is synthesized onto metals over a wide area is that it can not be separated from the metal. However, a groundbreaking separation technology which is both cheap and environment friendly has been developed.
Prof. Taek soo Kim and Prof. Byung Jin Cho"s research teams have conducted this research under the support of the Global Frontier program and Researcher Support Program initiated by The Ministry of Education and Science and Korea Research Foundation. The research results have been posted on the online news flash of Nano Letters on februrary 29th. (Thesis title: Direct Measurement of Adhesion Energy of Monolayer Graphene As-Grown on Copper and Its Application to Renewable Transfer Process)
The research has generated exact results on the interfacial adhesive energy of graphene and its surface material for the first time. Through this, the catalyst metal are no longer to be used just once, but will be used for an infinite number of times, thereby being ecofriendly and efficient.
Wide area graphine synthesized onto the catalyst meatal are used in various ways such as for display and for solar cells. There has been much research going on in this field. However, in order to use this wide area graphene, the graphene must be removed from the catalyst metal without damage.
Until now, the metal had been melted away through the use of chemical substances in order to separate the graphene. However, this method has been very problematic. The metal can not be reused, the costs are very high, much harmful wastes were created in the process of melting the metals, and the process was very complicated.
The research teams of Professors Taek Su Kim and Byung Jin Cho measured the interfacial adhesive energy of the synthesized graphene and learned that it could be easily removed.
Also, the mechanically removed graphene was successfully used in creating molecular electronic devices directly. This has thus innovatively shortened the graphene manufacturing process. Also, it has been confirmed that the metalic board can be reused multiple times after the graphene is removed. A new, ecofriendly and cost friendly method of graphene manufacturing has been paved.
Through this discovery, it is expected that graphene will become easier to manufacture and that the period til the commercialization date of graphene will therefore be greatly reduced
Prof. Cho stated " This reserach has much academical meaning significance in that it has successfully defined the surfacial adhesive energy between the graphene and its catalyst material and it should receive much attention in that it solved the largest technical problem involved in the production of graphene.
2012.04.04 View 12625
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New Era for Measuring Ultra Fast Phenomena: Atto Science Era
Domestic researchers successfully measured the exact status of the rapidly changing Helium atom using an atto second pulse. Thanks to this discovery, many ultrafast phenomena in nature can now be precisely measured. This will lead to an opening of a new "Atto Science" era.
Prof. Nam Chang Hee led this research team and Ph.d Kim Kyung Taek and Prof. Choi Nak Ryul also participated in this research. They have conducted the research under the support of the Researcher Support Program initiated by The Ministry of Education and Science and Korea Research Foundation. The research result was published in the prestigious journal "Physical Review Letters" on March 2nd. (Title: Amplitude and Phase Reconstruction of Electron Wave Packets for Probing Ultrafast Photoionization Dynamics)
Prof. Nam Chang Hee"s research team used atto second pulse to measure the ultrafast photoionization.
His team used atto second X-ray pulse and femto second laser pulse to photoionize Helium atoms, and measure the wave speed of the produced electron to closely investigate the ultrafast photoionization process.
Atom"s photoionization measurement using an atto second pulse was possible using the research team"s high-energy femto second laser and high-performance photo ion measurement device. This research team succeeded in producing the shortest 60 atto second pulse in the world using high-harmonic waves.
The research team used high-power femto second laser to produce atto second high-harmonic pulse from argon gas, used this to photoionize Helium atoms, and measured the ultrafast photoionization of the atoms.
Prof. Nam Chang Hee said, "This research precisely measured the exact status of rapidly changing Helium atoms. I am planning to research on measuring the ultrafast phenomena inside atoms and molecules and controlling the status of the atoms and molecules based on the research result."
2012.04.04 View 9607
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KAIST Confers Honorary Degree to CMU President Cohon
By DongJae Lee
The KAIST Herald Staff Reporter
On February 24, Dr. Jared L. Cohon, President of Carnegie Mellon University (CMU), visited KAIST to receive an honorary degree in science and technology and gave a lecture to the university’s students. Dr. Cohon is the eighth president of CMU and has held numerous other public and university positions. During his presidency, CMU has expanded globally and now takes part in joint programs around the world, including those with universities in Korea, Australia, India and Qatar. KAIST and CMU have been collaborating since 2005 in research projects, student and faculty exchange and dual degree programs. Before the 2012 Commencement Ceremony, Dr. Cohon met with The KAIST Herald and other news agencies for an interview.
The interview started with Dr. Cohon giving a brief introduction of CMU. Like KAIST, CMU has a small but special composition and is dedicated to science and technology as well as business and the fine arts. CMU, founded in 1900, is also relatively young by US standards but has nonetheless grown into a world-class university. The power behind this rapid growth can be expressed by four key values: innovation and change, problem-solving, interdisciplinary cooperation, and hard work. The slogan “My heart is in the work” clearly expresses the values of CMU.
One interesting aspect of CMU is its fine arts and business fields. While CMU is dedicated to science and technology, it also has many respected alumni in the aforementioned fields including Andy Warhol, a leading figure in pop art, and Randy Pausch, the author of The Last Lecture. CMU alumni have together won 6 Academy Awards, 22 Emmy Awards, over 100 Tony Awards and 20 Nobel Prizes.
Regarding CMU’s joint projects with KAIST, as well as student and faculty exchanges, Dr. Cohon mentioned joint Ph.D. programs in Civil and Environmental Engineering and Mechanical Engineering and a joint Master’s program in Software Engineering. Currently, the Civil and Environmental Engineering joint Ph.D. program has one participant and the Software Technology Institute joint Master of Software Engineering program has 6 participants.
Dr. Cohon mentioned that receiving an honorary degree in KAIST is a tremendous honor and that he is grateful to be recognized by such a wonderful university like KAIST.
2012.03.23 View 9928 -
Annual Future Knowledge Service International Symposium
Knowledge Service Research preparing for the future knowledge based society has been academically publicized.
The First Annual Future Knowledge Service International Symposium was held in COEX Grand Ball Room Hall by KAIST’s department of Knowledge Service Engineering.
Knowledge Service Engineering is a core component to the future knowledge based society and is the convergent result of decision making, recognition sciences, artificial intelligence, IT, and other knowledge management technologies from each of the industries. Therefore Knowledge Service Engineering will innovate the cooperation and communication between humans and machines thereby forming the center point of the development of knowledge society.
The symposium was attended by 9 important figures from domestic and foreign academia, government representative, and key figures from industries. The symposium was based around debates concerning the role of the Knowledge Service Engineering in the future knowledge based society.
The key note speaker was Chairman of Korea Science and Technology Information Research Institute Park Young Suh and the theme of the speech was ‘Change in Information Environment and Knowledge Service’.
Director of National IT Industry Promotion Agency Kang Hyun Gu gave a lecture on the topic of ‘Important Knowledge Service Policies by National IT Industry Promotion Agency’. And from industry experts, Bradley K. Jensen (Manager of Microsoft Industry-Education Cooperation), Lee Kang Yoon (Research Director at IBM), Choi Yoon Shik (Head of Asia Future Human Resource Institute) proposed a direction for research and gave their account on recent trends of knowledge service from the perspective of onsite experience.
Academic experts like Fred D. Davis (Professor at State University of Arkansas), Jussi Kantola (Professor at KAIST), Kim Young Gul (Professor at KAIST Management University), Yoon Wan Chul (Professor at KAIST Knowledge Service Engineering) gave the recent trends in academic research.
The symposium was held in 3 sessions: ▲Policy of Korean Government ▲Academic Research Trend ▲Recent Trend and Application.
More information can be found at http://kss.kaist.ac.kr
2012.01.31 View 8460
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Quantum Mechanical Calculation Theory Developed
An Electron Density Functional Calculation Theory, based on the widely used quantum mechanical principles and yet accurate and with shortened calculation period, was developed by Korean research team.
*Electron Density Functional Calculation Theory: Theory that proves that it is possible to calculate energy and properties with only simple wave equations and electron densities.
The research was conducted by Professor Jeong Yoo Sung (Graduate School of EEWS) and Professor William Goddard with support from WCU Foster Project initiated by Ministry of Education, Science and Technology and Korea Research Foundation. The result was published in the Proceedings of the National Academy of Sciences Journal.
The research team corrected the error when performing quantum calculations that arises from the length of calculation time and incorrect assumptions and developed a theory and algorithm that is more accurate and faster. The use of wave equations in quantum mechanical calculations results in high accuracy but there is a rapid increase in calculation time and is therefore difficult to implement in large molecules with hundreds, or thousands of atoms. By implementing a low electron density variable with relatively less calculation work, the size of calculable molecule increases but the accuracy decreases.
The team focused on the interaction between electrons with different spins to improve upon the speed of calculation in the conventional accurate calculation. The team used the fact that the interaction between electrons with different spins increases as it comes closer together in accordance with the Pauli’s Exclusion Principle.
In addition the interaction between electrons are local and therefore can ignore the interactions between far away electrons and still get the total energy value. The team also took advantage of this fact and developed the algorithm that decreased calculation time hundredth fold.
Professor Jeong commented that, “So far most of the domestic achievements were made by focusing on integrative researches by calculation science and material design communities but these involved short time frames. In areas that required lengthy time frames like fundamentals and software development, there was no competitive advantage. However this research is significant in that a superior solution was developed domestically”.
2012.01.31 View 10299