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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 11397 -
New wireless charging device developed
The On-line Electric Vehicle (OLEV) developed by KAIST has made a step towards commercialization with the development of a more economic wireless charging device.
Professor Chun-Taek Rim from the Department of Nuclear and Quantum Engineering at KAIST has developed a new I-shaped wireless charging device that differs from the pre-existing rail-type electricity feeder. This device can be modularly produced and requires relatively less construction, significantly reducing the cost of implementation.
The KAIST OLEV is a new concept electric car that has a special electricity collecting device underneath it. The car’s battery is charged by magnetic fields produced from electric lines buried 15cm underneath the road. The vehicle was first tested in 2009, making it the first wireless electric car in the world. OLEV can be charged during stoppage time between traffic lights and receives real-time power when running. OLEV is currently in operation at the KAIST Munji Campus in Daejeon and is also being exhibited at the Yeosu Expo and Seoul Grand Park.
The device itself has a charging capacity of 15kW, and the electricity is supplied through an electricity feeder with a width of 80cm with a space interval of 20cm. Despite being hailed as a technological breakthrough and revolutionary concept, KAIST OLEV has been criticized for problems in commercialization, due to the difficulties in installing wires beneath existing roads, which costs a considerable amount of money.
The new I-shaped wireless charging device reduces the width of the electricity feeder by 10cm, a mere one-eighth of the size of the previous version, and greatly increases the charging power to 25kW. Furthermore, the left and right permissible space of automobiles has increased to 24cm and the magnetic field complies with the international design guidelines, making the OLEV safe for the human body.
The reduction of the width has made the mass production of modules possible, making the installation of KAIST OLEV more economical and marketable. Professor Rim emphasized that compared with the existing rail-type electricity feeder, the new technology will need only one-tenth of the construction time and 80% of the cost, significantly improving OLEV’s constructability and workability.
The research was published in the IEEE Transactions on Power Electronics last December, and Professor Rim was invited to talk at the Conference on Electric Roads & Vehicles, which was held in February in the United States, about the new technology.
2012.07.06 View 11571
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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 11789
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President Nam Pyo Suh receives Honorary Doctorate from Bilkent University, Turkey
President of KAIST Nam Pyo Suh received an Honorary Doctorate from Turkey’s Bilkent University on June 13th, 2012.
Bilkent University revealed that it is President Suh’s invention of a plastic manufacture process used all over the world and the combination of academic achievements like the creation of the axiomatic design theory that merits the Honorary Doctorate.
After the presentation ceremony, President Suh gave a lecture to professors and students at Bilkent University on the "University of the Future: Changing Education Paradigm."
Bilkent University is located in Ankara, the capital of Turkey and was established in 1984, which is largely regarded as Turkey’s best private university. It ranked 32 out of 50 universities in Times Higher Educations’ 100 Under 50 List of World’s Best New Universities.
2012.06.18 View 8825 -
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 8742
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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 12798
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Korea's First MOU between a University Education Volunteer Work Group and Local Government
- 200 Adolescents from Yuseong-gu to Receive Education Community Services
Midam Scholarship committee which is composed of KAIST"s students and graduates, will draw up a contract that states that it will work together with the Yuseong-gu municipality for the development of the district education services on the 14th at the Yuseong-gu office.
Both sides will together ▲mentor the local students, ▲cooperate to run and develop creative programs, ▲exchange work for the development of the KAIST Midam Scholarship Committee, ▲conduct various other projects.
From now, the Midam Scholarship Committee will teach about 200 students in Yuseong-gu. The drawing of this contract has much meaning in that it is the first of its kind.
The Midam Scholarship Committee was founded on 2009 by students in KAIST to teach math, english, and science to students from families with low income levels.
This committee has made educational pacts with middle and high schools located in Daejeong such as Chungnam High School and Beobdong High School, and has not only taught these students but also has given scholarships to the selected students.
On one hand, the Midam Scholarship Committee has also supported 10 students in KAIST who were in need with 300000won each on the 6th. This fund was raised through the donations of alumni and mentoring projects.
The Midam Scholarship Committee has been recognized for its positive impacts on the society and has received an award from the Yuseong-gu municipality office.
2012.05.10 View 8794
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Professor Kyung Wook Baek Wins the Best Thesis Award at the 2012 Pan-Pacific Microelectronic Symposium
Prof. Kyung Wook Baek from KAIST"s material science department has won the Best Thesis Award at the 2012 Pan-Pacific Microelectronic Symposium.
The title of this thesis was "Recent Advances in Anisotropic Conductive Adhesives Technology : Materials and Processes". Prof Baek had the honor of having his thesis be appointed the best thesis of the symposium.
This thesis includes his 15 years of research on ACAs which are a key element of display and semiconductor packaging technology.
Prof. Baek"s research results has been recognized as incredibly innovative in the field of ACAs and ultrasonic connection devices. This thesis has been recognized as setting the foundation for commercialization by professionals from all over the world at the symposium.
Prof. Baek has announced two innovative technologies on ACAs at the symposium.
One is a technology that merges the nanofiber technology with the ATAs. This technology was highly applauded for overcoming the problem of electric connection in micro-pitch display semiconductors, and successfully applying this to electronic packaging materials.
Currently, commercialization process based on the patent is ongoing. It is expected that we will be able to take hold of the entire market once the commercialization succeeds.
The other technology was to improve the liability and overcome the limits of the current flow in ACAs through the use of solder molecules. This is also undergoing commercialization process for use in mobile electronic devices.
Together with this, Prof.Baek has reported an innovative case where the original heat compression process was replaced with a new ultrasonic process. This discovery is deemed to be extremely great due to its implications in replacing all heat compression systems. This too will soon be commercialized
Prof.Baek has played a crucial role in the development of electronic packaging material and processing technology. He has written the largest number of theses in this area, and has proven himself to be the world"s best through winning this award.
2012.05.10 View 9989
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KAIST Midam Institute Gives Donations Raised by Students
Midam Association which is consisted of students from KAIST (representatives Neung-in Jang and Minkyu Jin) has donated 300thousand won per person to ten KAIST students who are in need totaling a 3million won of donation. This donation was created through the mentoring activities of the members and donations from alumni and alumni corporations.
Midam Association which was created on July of 2009 teaches math, science, and English to children from lesser off families. It started as a club created by undergraduate students and has now turned into an NGO where other local volunteers could participate.
Currently as of March, there are ten schools including Bubdong Middle School, Jeon-min Middle School, Chungnam High School, and Jeonmin High School that have a pact with the Midam Association. The association has been conducting education assistance as well as giving donations to students in need.
Last January, UNIST has benchmarked KAIST"s Midam Association and has started free education volunteer programs in association with Ulsan city.
On the other hand, Midam Association of KAIST has been awarded a Certificate of Recognition by the Municipality of Yuseong-gu, Daejeon in recognition of their deed.
2012.05.10 View 8310
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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 14497 -
High-resolution Atomic Imaging of Specimens in Liquid Observed by Transmission Electron Microscopes Using Graphene Liquid Cells
Looking into specimens in liquid at the atomic level to understand nanoscale processes so far regarded as impossible to witnessThe Korea Advanced Institute of Science and Technology (KAIST) announced that a research team from the Department of Materials Science and Engineering has developed a technology that enables scientists and engineers to observe processes occurring in liquid media on the smallest possible scale which is less than a nanometer.
Professor Jeong Yong Lee and Researcher Jong Min Yuk, in collaboration with Professors Paul Alivisatos’s and Alex Zettl’s groups at the University of California, Berkeley, succeeded in making a graphene liquid cell or capsule, confining an ultra-thin liquid film between layers of graphene, for real-time and in situ imagining of nanoscale processes in fluids with atomic-level resolution by a transmission electron microscope (TEM). Their research was published in the April 6, 2012 issue of Science. (http://www.sciencemag.org/content/336/6077/61.abstract)
The graphene liquid cell (GLC) is composed of two sheets of graphene sandwiched to create a sealed chamber where a platinum growth solution is encapsulated in the form of a thin slice. Each graphene layer has a thickness of one carbon atom, the thinnest membrane that has ever been used to fabricate a liquid cell required for TEM.
The research team peered inside the GLC to observe the growth and dynamics of platinum nanocrystals in solution as they coalesced into a larger size, during which the graphene membrane with the encapsulated liquid remained intact. The researchers from KAIST and the UC Berkeley identified important features in the ongoing process of the nanocrystals’ coalescence and their expansion through coalescence to form certain shapes by imaging the phenomena with atomic-level resolution.
Professor Lee said,
“It has now become possible for scientists to observe what is happening in liquids on an atomic level under transmission electron microscopes.”
Researcher Yuk, one of the first authors of the paper, explained his research work.
“This research will promote other fields of study related to materials in a fluid stage including physical, chemical, and biological phenomena at the atomic level and promises numerous applications in the future. Pending further studies on liquid microscopy, the full application of a graphene-liquid-cell (GLC) TEM to biological samples is yet to be confirmed. Nonetheless, the GLC is the most effective technique developed today to sustain the natural state of fluid samples or species suspended in the liquid for a TEM imaging.”
The transmission electron microscope (TEM), first introduced in the 1930s, produces images at a significantly higher resolution than light microscopes, allowing users to examine the smallest level of physical, chemical, and biological phenomena. Observations by TEM with atomic resolution, however, have been limited to solid and/or frozen samples, and thus it has previously been impossible to study the real time fluid dynamics of liquid phases.
TEM imaging is performed in a high vacuum chamber in which a thin slice of the imaged sample is situated, and an electron beam passes through the slice to create an image. In this process, a liquid medium, unlike solid or frozen samples, evaporates, making it difficult to observe under TEM.
Attempts to produce a liquid capsule have thus far been made with electron-transparent membranes of such materials as silicon nitride or silicon oxide; such liquid capsules are relatively thick (tens to one hundred nanometers), however, resulting in poor electron transmittance with a reduced resolution of only a few nanometers. Silicon nitride is 25 nanometers thick, whereas graphene is only 0.34 nanometers.
Graphene, most commonly found in bulk graphite, is the thinnest material made out of carbon atoms. It has unique properties such as mechanical tensile strength, high flexibility, impermeability to small molecules, and high electrical conductivity. Graphene is an excellent material to hold micro- and nanoscopic objects for observation in a transmission electron microscope by minimizing scattering of the electron beam that irradiates a liquid sample while reducing charging and heating effects.
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Figure 1. Schematic illustration of graphene liquid cells. Sandwiched two sheets of graphene encapsulate a platinum growth solution.
Figure 2. In-situ TEM observation of nanocrystal growth and shape evolution. TEM images of platinum nanocrystal coalescence and their faceting in the growth solution.
2012.04.23 View 11963 -
International workshop on healthcare technology to be held on campus, April 24, 2012
KAIST and the KTH Royal Institute of Technology (KTH), Sweden, host a joint workshop on healthcare technologies on Tuesday, April 24, at the LG Semicon Hall (N24).
Open to the public, the workshop will proceed with presentations and discussions by participants from both institutions. Presentation topics and speakers are as follows:
“Applied medical engineering, innovation from clinical problems” by Professor Lars-Åke Brodin, Dean of School of Technology and Health, KTH
“ICT in healthcare” by Professor Björn-Erik Erlandsson, School of Technology and Health, KTH
“Department of environmental physiology, human research in extreme environments” by Researcher Mikael Grönkvist, School of Technology and Health, KTH
“Brain function imaging using high-resolution MRI technology” by Professor Hyun Wook Park, Department of Electrical Engineering, KAIST
“Bioinstrumentation for healthcare and physical human robot interactions” by Professor Jung Kim, Division of Mechanical Engineering, KAIST
“A portable high-resolution near-infrared spectroscopy system” by Professor Hyeon-Min Bae, Department of Electrical Engineering, KAIST
“Lab-on-a-chip technologies for integrative bioengineering” by Professor Je-Kyun Park, Department of Bio and Brain Engineering, KAIST
“The cytoskeleton in cancer and regulation by oncogenic signaling” by Professor David M. Helfman, Department of Biological Sciences, KAIST
Professor Chang Dong Yoo, Associate Vice President of Office of Special Projects and Institutional Relations at KAIST, who organized the workshop, says “Aging population and health issues are driving the demand for more sophisticated medical devices, procedures, and most importantly, qualified scientists and engineers specialized in health-related fields. This joint workshop will be a great chance to share new ideas and develop joint research between two leading research-oriented universities in two countries.”
Partially supported by LG Ericsson in Korea, the workshop is funded largely by the generous donation, made last June by a Swedish couple, to KAIST scholar exchange program.
The couple (Rune Jonasson and Kerstin Jonasson) donated 70 million krona (about 11.8 billion Korean won) to KTH last year and requested that some portion of the sum be used for a scholar exchange program with KAIST. The wife of the couple, Kerstin Jonasson, participated in the Korean War as a nurse, and upon her wish for further development in Korea’s science and technology, KAIST and KTH decided to use the donation for research in the field of healthcare and for a post-doc researcher exchange program.
KTH is a world-class university of Sweden and has produced numerous researchers for private enterprises, like Ericsson, and venture businesses. Since 1988, KTH offers a top notch program for information technology; the School of Information and Communication Technology is located in the Kista district, a vibrant cluster of information and communications technology industries in Sweden, and has taken on the crucial role of supplying personnel to the Kista Science Park as well as to academic-industrial cooperation.
For any inquiries, please contact the International Relations Team at +82-42-350-2441 (email: jungillee@kaist.ac.kr).
2012.04.21 View 11216