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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.
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
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 (firstname.lastname@example.org, +82-42-350-3930)
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
Creation of Synthetic Antibodies: Professor Hak Seong Kim
Synthetics antibodies which can replace antibodies from humans used as ingredients of medicines have been developed. It can increase the costs to 1/100 of the current costs and is much easier to develop. It is expected that the development period will be shortened from 10 years to 5. Prof. Hak Seong Kim from the Biology department of KAIST conducted a joint research with Prof. Dong Seob Kim to reconstruct proteins and has succeeded. The synthetic antibody displays much strength in terms of its productivity, structural formation, and bonding capability, and is thus regarded as an ideal protein. It can replace the antigens that are currently in use. It is expected that Korea will therefore be able to lead the world market for protein medicines which is a 192trillion won industry. The original antibody has been used for not only treating diseases, but also for various other applications in the fields of medical sciences and biology. However, it is produced through a very complex process involving the incubation of animal cells, and is therefore very expensive. Also, most antibodies are already patented by more developed countries, so a high royalty fee must be paid. Because of this, many countries including Korea has been concentrating on developing biosimilars copying the antibody medicines for which the patents have already expired. This causes Korea to be behind in the development of antibody protein pharmaceuticals. Prof. Kim’s research team has focused on the face that the protein existing in some eels are not antibodies but functions as one, and has been successful in developing a synthetic antibody. The synthetic antibody can be mass produced from the colon bacillus, which allows it to be produced at 1/100 the original cost. It is in a module structure which allows the structuring of the antibody into the desired structure, enabling it to be developed into a protein-based medicine within 5 years. Together with this, the coherence with the important antigens can be easily controlled, thus allowing for highly effective treatments, less side-effects, high security regarding heat and pH, and the immunogen levels being negligeable. This suggests a very high rate of the antibody being converted into a protein based medication. The synthetic antibody technology has been tested as a sample for the cure for lung diseases and rheumatism and has been proven to be appropriate. Animal testing will be conducted soon. Prof Kim said “The original antibodies had a small area allowing the bonding with antibodies, creating barriers for raising bonding strength and structuring. The newly created antibody carries only the strengths and will become a new protein based medicine purely created by Korean technology to replace the antibodies currently used in medications.” Furthermore, he added that, “The synthesized antibody structuring and designing technology will be widely used in the areas of detecting, diagnosing, and analyzing diseases.” At the same time, this research result has been published in the Feb 10th issue of the PNAS, and has been supported by the future promising pioneer business program held by the Ministry of Education and Technology.
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.
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."
Bio Pharmaceutical Business Center: Now Open
The Signboard Hanging Ceremony for the Bio Pharmaceutical Business Center for the Integrated Research for the field of Bio Pharmaceutics. 150 representatives from various bio pharmaceutics related businesses and institutes were present for this ceremony. The Ministry of Education, Science and Technology placed the Molecular Process research team, Personalized Drug Delivery Medium research team, and the newly formed Cancer Cell Detection using Blood research team at the Bio Pharmaceutical Business Center at KAIST.
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”.
2011 International Presidential Forum on Global Research Universities
KAIST’s 4th International Presidential Forum Held in Seoul on November 8, 2011 The largest annual congregation of university presidents in Asia invited leaders from academia, government, and industry for talks on issues related to higher education in the Age of Globalization. Borderless and Creative Education: the ability to cross borders a crucial key to dominate the information era Seoul, Republic of Korea, November 8, 2011—The Korea Advanced Institute of Science and Technology (KAIST) hosted the “2011 International Presidential Forum on Global Research Universities (IPFGRU)” on Tuesday, November 8, 2011 at the Millennium Hilton Hotel in Seoul. With more than 120 participants from 44 institutions in 27 countries present, the full-day forum provided participants with an opportunity to discuss challenges and responsibilities facing higher education in a time of globalization that has resulted from an ever-growing demand for technological innovation. In his plenary speech, Dr. Robert Birgeneau, Chancellor of UC Berkeley, stressed that “Higher educational intuitions must be prepared to drive innovation and enhance competitiveness by educating a highly trained workforce that will have the critical skills necessary to solve problems and lead in today’s interdependent world.” “Finding solutions to the world’s most challenging problems will depend on the ability to cross borders: national borders, border between different fields of discipline and research, and borders between academe, government, and industry,” said Chancellor Birgeneau to address the importance of “borderless and creative education,” the theme of the forum. Other major keynote speakers were Jörg Steinbach, President of Technische Universität Berlin, Lars Pallesen, President of Technical University of Denmark, Paul F. Greenfield, President of University of Queensland, Marcelo Fernandes de Aquino, President of the University of the Sinos Valley (UNISINOS), and Eden Woon, Vice President of the Hong Kong University of Science and Technology. Dr. Nam-Pyo Suh, President of KAIST, gave talks on the university’s new education plan, “The I-Four Education,” at the afternoon session. The four Is are information technology (IT), independent learning, integrated knowledge acquisitions, and an international learning environment. “In this format, there are no formal lectures,” President Suh explained. “A group of students learn together by using the materials available on the internet, doing homework and conducting experiments together. Pre-recorded lectures are delivered in English by I-Four professors, some of them regular KAIST professors and some professors in other countries who participate in the I-Four Program as consulting professors.” He added, “The overall purpose of the I-Four Education Program is to encourage students to learn independently, gain exposure to the best lectures by the most eminent professors in the world, accelerate the development of a global frame of reference in the students by dealing with information available throughout the world, and provide an integrated learning environment by using diverse examples from many disciplines to achieve understanding of basic principles.” The 2011 IPFGRU, the fourth forum since its inception in 2008, rose to prominence in the past years as an international network for leaders of research universities from around the world to share information and exchange views about contemporary issues in higher education. At this year’s forum, entitled “Borderless and Creative Education,” speakers took a deeper look into the transitions and transformations many research universities are undergoing today, delving into the following topics: the development of e-learning and cyber campuses; increased student mobility and international collaborations; multi-disciplinary and convergence approaches in research and education; and methodology of nurturing future global leaders. Participants also discussed experiences and accomplishments earned from their own endeavors to accommodate such changes and presented ways to strengthen internationalization and improve the academic and research competitiveness of universities. The 2011 International Presidential Forum on Global Research Universities (IPFGRU) was organized by KAIST and sponsored by the Ministry of Education, Science and Technology, POSCO, Hyundai Motor Company, Samsung Heavy Industries, S-Oil, and Elsevier Korea.
KAIST paves the way to commercialize flexible display screens
Source: IDTechEX, Feb. 28, 2011 KAIST paves the way to commercialize flexible display screens 28 Feb 2011 Transparent plastic and glass cloths, which have a limited thermal expansion needed for the production of flexible display screens and solar power cells, were developed by researchers at KAIST (Korea Advance Institute of Science & Technology). The research, led by KAIST"s Professor Byoung-Soo Bae, was funded by the Engineering Research Center under the initiative of the Ministry of Education, Science and Technology and the National Research Foundation. The research result was printed as the cover paper of "Advanced Materials". Professor Bae"s team developed a hybrid material with the same properties as fiber glass. With the material, they created a transparent, plastic film sheet resistant to heat. Transparent plastic film sheets were used by researchers all over the world to develop devices such as flexible displays or solar power cells that can be fit into various living spaces. However, plastic films are heat sensitive and tend to expand as temperature increases, thereby making it difficult to produce displays or solar power cells. The new transparent, plastic film screen shows that heat expansion index (13ppm/oC) similar to that of glass fiber (9ppm/oC) due to the presence of glass fibers; its heat resistance allows to be used for displays and solar power cells over 250oC. Professor Bae"s team succeeded in producing a flexible thin plastic film available for use in LCD or AMOLED screens and thin solar power cells. Professor Bae commented, "Not only the newly developed plastic film has superior qualities, compared to the old models, but also it is cheap to produce, potentially bringing forward the day when flexible displays and solar panels become commonplace. With the cooperation of various industries, research institutes and universities, we will strive to improve the existing design and develop it further." http://www.printedelectronicsworld.com/articles/kaist_paves_the_way_to_commercialize_flexible_display_screens_00003144.asp?sessionid=1
Professor Min Beom Ki develops metamaterial with high index of refraction
Korean research team was able to theoretically prove that a metamaterial with high index of refraction does exist and produced it experimentally. Professor Min Beom Ki, Dr. Choi Moo Han, and Doctorate candidate Lee Seung Hoon was joined by Dr. Kang Kwang Yong’s team from ETRI, KAIST’s Professor Less Yong Hee’s team, and Seoul National University’s Professor Park Nam Kyu’s team. The research was funded by the Basic Research Support Program initiated by the Ministry of Education, Science, and Technology and Korea Research Federation. The result of the research was published in ‘Nature’ magazine and is one of the few researches carried out by teams composed entirely of Koreans. Metamaterials are materials that have physical properties beyond those materials’ properties that are found in nature. It is formed not with atoms, but with synthetic atoms which have smaller structures than wavelengths. The optical and electromagnetic waves’ properties of metamaterials can be altered significantly which has caught the attention of scientists worldwide. Professor Min Beom Ki’s team independently designed and created a dielectric metamaterial with high polarization and low diamagnetism with an index of refraction of 38.6, highest synthesized index value. It is expected that the result of the experiment will help develop high resolution imaging system and ultra small, hyper sensitive optical devices.
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