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Light Driven Drug-Enzyme Reaction Catalytic Platform Developed
Low Cost Dye Used, Hope for Future Development of High Value Medicinal Products to Treat Cardiovascular Disease and Gastric Ulcers
A KAIST research team from the Departments of Materials Science and Engineering and of Chemical and Biomolecular Engineering, led respectively by Professors Chan Beum Park and Ki Jun Jeong, has developed a new reaction platform to induce drug-enzyme reaction using light.
The research results were published in the journal Angewandte Chemie, International Edition, as the back cover on 12 January 2015.
Applications of this technology may enable production of high value products such as medicine for cardiovascular disease and gastric ulcers, for example Omeprazole, using an inexpensive dye.
Cytochrome P450 is an enzyme involved in oxidative response which has an important role in drug and hormone metabolism in organisms. It is known to be responsible for metabolism of 75% of drugs in humans and is considered a fundamental factor in new drug development.
To activate cytochrome P450, the enzyme must receive an electron by reducing the enzyme. In addition, NADPH (a coenzyme) needs to be present. However, since NADPH is expensive, the use of cytochrome P450 was limited to the laboratory and has not yet been commercialized.
The research team used photosensitizer eosin Y instead of NADPH to develop “Whole Cell Photo-Biocatalysis” in bacteria E. coli. By exposing inexpensive eosin Y to light, cytochrome P450 reaction was catalyzed to produce the expensive metabolic material.
Professor Park said, “This research enabled industrial application of cytochrome P450 enzyme, which was previous limited.” He continued, “This technology will help greatly in producing high value medical products using cytochrome P450 enzyme.”
The research was funded by the National Research Foundation of Korea and KAIST's High Risk High Return Project (HRHRP).
Figure 1: Mimetic Diagram of Electron Transfer from Light to Cytochrome P450 Enzyme via Eosin Y, EY
Figure 2: The back cover of Angewandte Chemie published on 12 January 2015, showing the research results
2015.01.26 View 10510 -
KAIST Announces the Recipients of Distinguished Alumni Awards
The KAIST Alumni Association (KAA) announced four “Proud KAIST Alumni” awards recipients for the year 2014: Sung-Wook Park, the Chief Executive Officer and President of SK Hynix; Seung Ho Shin, the President of Kangwon National University; Kew-Ho Lee, the President of the Korea Research Institute of Chemical Technology; and Mun-Kee Choi, the former Minister of Science, ICT and Future Planning of the Republic of Korea. The award ceremony took place during the 2015 KAA’s New Year's ceremony on January 17, 2015 at the Palace Hotel in Seoul.
Sung-Wook Park (M.S. ’82 and Ph.D. ’88, Department of Materials Science and Engineering), the Chief Executive Officer and President of SK Hynix, has worked as an expert in the field of memory semi-conductors for the past 30 years. He developed innovative technology and improved production efficiency, enabling the Korean semi-conductor industry to become a global leader.
Seung Ho Shin (M.S. ’79 and Ph.D. ’87, Department of Physics), the President of Kangwon National University (KNU), worked in the field of optical information processing, producing excellent research achievements and teaching the next generation of scientists. As the president of KNU, he has set an exemplary leadership in higher education.
Kew-Ho Lee (M.S. ’75, Department of Chemistry), the President of the Korea Research Institute of Chemical Technology, pioneered the field of separation film production which contributed greatly to Korean technological developments. He led several domestic and international societies to facilitate dynamic exchanges between industry and academia and with the international community.
Mun-Kee Choi (M.S. ’76, Department of Industrial and Systems Engineering), the former Minister of Science, ICT and Future Planning, the Republic of Korea, is a great contributor to the information and communications technology in Korea, working as a leader in the field of broadband integrated service digital network. He is also an educator for gifted students in science and technology, and a manager of the Electronics and Telecommunications Research Institute.
The Alumni Association established the “Proud KAIST Alumni Awards” in 1992 to recognize its alumni’s outstanding contributions to Korea and KAIST.
Pictured from left to right, Sung-Wook Park (the Chief Executive Officer and President of SK Hynix), Seung Ho Shin (the President of Kangwon National University), Kew-Ho Lee (the President of the Korea Research Institute of Chemical Technology), and Mun-Kee Choi (the former Minister of Science, ICT and Future Planning)
2015.01.19 View 14485 -
Hierarchically-Porous Polymers with Fast Absorption
KAIST's Professor Myungeun Seo and his research team from the Graduate School of Nanoscience and Technology has developed a method to form micropores of less than 2 nanometers within porous polymers where 10 nanometers long mesopores connect like a net. The advantage of the porous polymers is fast absorption of molecules.
Porous polymers with micropores of less than 2 nanometers, like a zeolite, have a large surface area. They are used as a means to store hydrogen-based molecules or as a catalytic support that can be used as a surface to convert a material into a desired form. However, because the size of the pores in its path was too small for the molecules, it took a long time to spread into the pores and reach the surface.
To reach the surface efficiently, a lung cell or the vein of a leaf has a structure wherein the pores are subdivided into different sizes so that the molecule can spread throughout the organ. A technology that can create not only micropores but also bigger pores was necessary in order to create such structure.
The research team solved the issue by implementing a "self-assembly" of block polymers to easily form a net-like nanostructure from mesopores of 10 nanometers.
The team created hierarchically-porous polymers consisting of two different types of pores by using a hypercrosslinking reaction along with the "self-assembly" method. The reaction creates micropores within the chain after the polymer chain is confined by a chemical bond.
This porous polymer has micropores that are smaller than 2 nanometers on the walls of mesopores while 10 nanometers long mesopores forming 3-dimensional net structures. Because of the "self-assembly" method, the size of mesopores can be adjusted within the range of 6 to 15 nanometers.
This is the first case where a porous polymer has both well-defined mesopores and micropores. The research team verified the effect of hierarchically-porous structures on absorption of molecules by confirming that the porous polymer had faster absorption speeds than a polymer consisting only of micropores.
Professor Seo said, “The study has found a simple way to create different sizes of pores within a polymer.” He expected that the hierarchically-porous polymers can be used as a catalytic support in which fast diffusion of molecules is essential, or for molecule collection.
The research was sponsored by National Research Foundation of Korea and published online in the Journal of the American Chemical Society.
Figure 1 – Net-like Structure of Hierarchically-Porous Polymers with Mesopores and Micropores on the walls of Mesopores.
Figure 2 - Hierarchically-Porous Polymers
Figure 3 – Comparison of Porous-Polymers consisting of Mesopores only (left), and Mesopores and Micropores (right)
2015.01.13 View 8800 -
An Advanced Method of DNA Nanostructure Formation Developed
Professor Tae-Young Yoon’s research team from the Department of Physics at KAIST has developed a new method to form DNA nanostructures by using magnetic tweezers to observe and to induce the formation of the structure in real time.
Unlike traditional designs of "DNA origami" which relies on thermal or chemical annealing methods, the new technology utilizes a completely different dynamic in DNA folding. This allows the folding to be done within only ten minutes.
Developed in 2006, the "DNA origami" allows a long skeleton of DNA to be folded into an arbitrary structure by using small stapler DNA pieces. This has been a prominent method in DNA nanotechnology.
However, the traditional technology which adopts thermal processes could not control the DNA formation during the folding because every interaction among DNAs occurs simultaneously. Thus, the thermal processes, which take dozens of hours to complete, had to be repeated multiple times in order to find the optimal condition.
The research team designed a DNA folding using uni-molecular magnetic tweezers that applied force to a single DNA molecule while measuring the state of the DNA. Through this technology, they were able to induce the formation of DNA nanostructure and observe it at the same time.
During high temperature heat treatment, the first stage of conventional thermal processes, the internal structure of the long skeleton DNA untangles. To induce such state, after attaching one side of the skeleton DNA to the surface of glass and the other side to a magnetic material, the team unfolded the internal structure of the DNA by pulling the two sides apart with magnetic force.
Unlike the conventional thermal processes, this method lets the stapler DNA swiftly adhere to the skeleton DNA within a minute because the sites are revealed at room temperature.
After the stapler pieces connected to the skeleton, the team removed the magnetic force. Next, the structure folded through self-assembly as the stapler DNAs stuck to different sites on the skeleton DNA.
Professor Yoon said, “With the existing thermal methods, we could not differentiate the reactions of the DNA because the response of each DNA pieces mutually interacted with each other.” He added that “Using the magnetic tweezers, we were able to sort the process of DNA nanostructure formation into a series of reactions of DNA molecules that are well known, and shorten the time taken for formation in only ten minutes.”
He commented, “This nanostructure formation method will enable us to create more intricate and desirable DNA nanostructures by programming the folding of DNA origami structures.”
Conducted by Dr. Woori Bae under the guidance of Professor Yoon, the research findings were published online in the December 4th issue of Nature Communications.
Figure 1: Uni-molecular magnetic tweezers orchestrating the DNA nanostructure formation
Figure 2: The evolution of DNA nanostructure formation using magnetic tweezers. The DNA nanostructure with a 21-nanometer size was formed in about eight minutes.
2015.01.06 View 7407 -
Professor Eunjoon Kim Is KAIST's Person of the Year 2014
KAIST announced that it has named Chair Professor Eunjoon Kim of the Department of Biological Sciences as its “Person of the Year 2014.” The award ceremony took place at the auditorium on campus on January 5, 2014.
Established in 2001, the award has been presented to a KAIST faculty member who has made great achievements in research and education, thereby contributing to the advancement of KAIST.
Professor Kim was the first to identify the mechanism of synapse formation between neurons during his post-doctoral program at Harvard Medical School in 1995. The research was published in Nature.
In 2011, Professor Kim discovered that the lack of protein GIT1, a neuronal synapse in the brain, caused ADHD (Attention Deficit Hyperactivity Disorder). He is widely recognized for his work concerning synapse proteins and brain disease related research that set the foundation for future medical developments.
In his award speech, Professor Kim said, “Whenever a research finding concerning a new drug therapy or research is published, I receive many inquiries from the parents of children with ADHD or autism. As a scientist, I would like to focus my research ultimately to help those in pain, rather than just pursuing research excellence or reputation.”
2015.01.06 View 10483 -
The Graduate School of Green Growth at KAIST Holds a Student Conference
The Graduate School of Green Growth at KAIST hosted a student conference on December 22, 2014 at the Seoul campus of the College of Business. About 100 master’s and doctoral students joined the conference held under the theme of “Green Knowledge Hub” and presented their research papers.
At the conference, three students received awards. The author of a paper entitled “Development and Analysis of Climate Change Vulnerability Index Applicable to Developing Countries” received the grand prize. The authors of “Green IT and Its Case Study on the Reduction of Greenhouse Gas Emissions by Industry” and “Analysis of Correlation between Consumers’ Subjective Happiness and Their Green Purchasing” were selected for runner-up prizes, respectively.
Dean Jae-Kyu Lee of the Green Growth Graduate School said, “We offered the conference to our students to engage with their peers and share ideas and knowledge in their majors. I hope students become more motivated, and we will continue holding this event in the future.”
2015.01.05 View 7057 -
A Key Signal Transduction Pathway Switch in Cardiomyocyte Identified
A KAIST research team has identified the fundamental principle in deciding the fate of cardiomyocyte or heart muscle cells. They have determined that it depends on the degree of stimulus in β-adrenergic receptor signal transduction pathway in the cardiomyocyte to control cells' survival or death. The findings, the team hopes, can be used to treat various heart diseases including heart failure.
The research was led by KAIST Department of Bio and Brain Engineering Chair Professor Kwang-Hyun Cho and conducted by Dr. Sung-Young Shin (lead author) and Ph.D. candidates Ho-Sung Lee and Joon-Hyuk Kang. The research was conducted jointly with GIST (Gwangju Institute of Science and Technology) Department of Biological Sciences Professor Do-Han Kim’s team. The research was supported by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. The paper was published in Nature Communications on December 17, 2014 with the title, “The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes.”
The β-adrenergic receptor signal transduction pathway can promote cell survival (mediated by β2 receptors), but also can result in cell death by inducing toxin (mediated by β1 receptors) that leads to various heart diseases including heart failure. Past attempts to identify the fundamental principle in the fate determining process of cardiomyocyte based on β-adrenergic receptor signalling concluded without much success.
The β-adrenergic receptor is a type of protein on the cell membrane of cardiomyocyte (heart muscle cell) that when stimulated by neurohormones such as epinephrine or norepinephrine would transduce signals making the cardiomyocyte contract faster and stronger.
The research team used large-scale computer simulation analysis and systems biology to identify ERK* and ICER** signal transduction pathways mediated by a feed-forward circuit as a key molecular switch that decides between cell survival and death.
Weak β-adrenergic receptor stimulations activate ERK signal transduction pathway, increasing Bcl-2*** protein expression to promote cardiomyocyte survival. On the other hand, strong β-adrenergic receptor stimulations activate ICER signal transduction pathway, reducing Bcl-2 protein expression to promote cardiomyocyte death.
Researchers used a systems biology approach to identify the mechanism of B-blocker****, a common drug prescribed for heart failure. When cardiomyocyte is treated with β1 inhibitor, strong stimulation on β-adrenergic receptor increases Bcl-2 expression, improving the chance of cardiomyocyte survival, a cell protection effect.
Professor Kwang-Hyun Cho said, “This research used systems biology, an integrated, convergence research of IT (information technology) and BT (biotechnology), to successfully identify the mechanism in deciding the fate of cardiomyocytes based on the β-adrenergic receptor signal transduction pathway for the first time. I am hopeful that this research will enable the control of cardiomyocyte survival and death to treat various heart diseases including heart failure.”
Professor Cho’s team was the first to pioneer a new field of systems biology, especially concerning the complex signal transduction network involved in diseases. Their research is focused on modelling, analyzing simulations, and experimentally proving signal pathways. Professor Cho has published 140 articles in international journals including Cell, Science, and Nature.
* ERK (Extracellular signal-regulated kinases): Signal transduction molecule involved in cell survival
** ICER (Inducible cAMP early repressor): Signal transduction molecule involved in cell death
*** Bcl-2 (B-cell lymphoma 2): Key signal transduction molecule involved in promotion of cell survival
**** β-blocker: Drug that acts as β-adrenergic receptor inhibitor known to slow the progression of heart failure, hence used most commonly in medicine.
Picture: A schematic diagram for the β-AR signalling network
2015.01.05 View 13593 -
Professor Mikyoung Lim Receives the MediaV Young Researcher Award
Professor Mikyoung Lim of the Department of Mathematical Sciences at KAIST received the MediaV Young Researchers Award at the International Conference on Inverse Problems and Related Topics that took place at the National Taiwan University, Taiwan, on December 15-19, 2014.
The Conference established the MediaV Young Researcher Award in 2010 to recognize distinguished scholars who are age 40 or younger and have made important contributions to the field of inverse problems. This year, two recipients were chosen for the award.
Professor Lim has focused her research on the incremental reading of incomprehensible materials’ imaging and the effect of invisibility cloaking.
The other awardee was Kui Ren, a professor at the University of Texas at Austin.
2014.12.27 View 10973 -
KAIST wins second place in unmanned boat competition
KAIST took second place in an international competition to promote technologies of the autonomous underwater vehicle (AUV).
Professor Jin-hwan Kim’s research team from KAIST’s Ocean Systems Engineering Department won the second place in Maritime RobotX Challenge which took place for the first time from October 20 - 26 in Marina Bay, Singapore.
Along with automobiles and drones, the necessity for unmanned boats has grown. To encourage and examine the development of these technologies, the U.S. Office of Naval Research decided to organize an unmanned boat competition which took place for the first time this year.
After three teams were selected from a domestic competition in each countries, a total of fifteen teams from five countries from the Pacific Rim including Korea, the United States, Australia, Japan, and Singapore competed. Teams from such universities as MIT, Tokyo University, Tokyo Institute of Technology, National University of Singapore, Nanyang Technological University, and Queensland University of Technology participated. In addition to KAIST, Seoul National University and Ulsan University participated.
Using a 4.5 meters long and 2.5 meters wide unmanned boat provided by the organizer, each team had to implement an integrated system that combined a propulsion system, hardware, and autonomous software. Each team’s vessel had to perform tasks without manual control, employing autonomous driving through recognition of the course, searching underwater for acoustic sources, automatically approaching piers, remote observation of buoy, and avoidance and detection of obstacles.
Although KAIST outpaced MIT in the semifinal which selected six out of fifteen teams, it won the second place in the final. As well as winning second prize, KAIST also won best website prize and a special prize from the competition sponsor, Northrop Grumman Corporation, an American defense technology company, totaling 16,500 U.S. dollars of prize money.
The Vice President for Planning and Budget, Professor Seungbin Park said, “It was a great opportunity to showcase the advanced unmanned robot technology of Korea.” He added that “this raised KAIST’s reputation as a global research oriented university.”
Professor Kim commented, “Along with automobiles and drones, the necessity for the development of unmanned ocean vehicles such as unmanned boats and submarines are recognized these days.” He added that “the use of unmanned boats will make the process of channel investigation, ocean exploration, surveillance over water territories safer and more effective.”
Professor Kim’s team was sponsored by the U.S. Office of Naval Research, Samsung Heavy Industries, Sonar Tech, Daeyang Electric, and Red-one Technology.
KAIST Team's Unmanned Boat
The Competition's Missions
2014.12.12 View 11579 -
KAIST Establishes a Center for Human Rights and Ethics
KAIST hosted an opening ceremony on November 27, 2014 for its Center for Human Rights and Ethics (CHRE) located in the Education Support Building on campus.
President Steve Kang and other senior administrators participated in the ceremony, pledging to eliminate violence, corruption, and prejudice on the campus.
The CHRE was created to provide members of the KAIST community with one-stop service to report and process human rights violation cases and issues related to corruption and illegalities such as verbal abuse, physical assault, sexual harassment, and bribes. The center will also launch campaigns to promote and strengthen awareness of human rights and ethics within the university.
The Director of CHRE, Professor Young-hee Kim of the Department of Humanities and Social Sciences at KAIST said, “The center will serve an important role in the improvement of human rights and in the reestablishment of moral standards in KAIST. I hope KAIST members make the most of the center wherever they face injustice and unequal treatment during their study and work at the campus.”
2014.12.08 View 7069 -
KAIST Partners with Science-focused Universities in Korea for Student Exchange Programs
KAIST and four science-focused universities in Korea (Pohang University of Science and Technology, Gwangju Institute of Science and Technology, Daegu Gyeongbuk Institute of Science and Technology, and Ulsan National Institute of Science and Technology) agreed to exchange programs during academic semesters including summer and winter terms by signing a memorandum of understanding (MOU) on November 28, 2014. The signing ceremony took place at the KAIST campus with the participation of academic affairs deans from all five universities.
Based on the agreement, KAIST students can take up to 12 credits of coursework at any of the said universities and have unimpeded access to the university facilities during their coursework.
Dean Hyun-Wook Park of Academic Affairs at KASIT said, “Through exchange programs, students can capitalize on each university’s advantages, and this eventually will lead to greater advancement in science and technology in the nation.”
2014.12.08 View 8161 -
Nanoparticle Cluster Manufacturing Technique Using DNA Binding Protein Developed
Professor Hak-Sung Kim of the Department of Biological Sciences at KAIST and Yiseul Ryu, a doctoral candidate, used the Zinc Finger protein that specifically binds to target DNA sequence to develop a new manufacturing technique for size-controllable magnetic Nanoparticle Clusters (NPCs). Their research results were published in Angewandte Chemie International Edition online on 25 November 2014.
NPCs are structures consisting of magnetic nanoparticles, gold nanoparticles, and quantum dots, each of which are smaller than 100 nm (10-9m). NPCs have a distinctive property of collectivity not seen in single nanoparticles.
Specifically NPCS differ in physical and optical properties such as Plasmon coupling absorbance, energy transfers between particles, electron transfers, and conductivity. Therefore, NPCs can be employed in biological and medical research as well as the development of nanoelectric and nanoplasmon devices.
To make use of these novel properties, the size and the composition of the cluster must be exquisitely controlled. However, previous techniques relied on chemical binding which required complex steps, making it difficult to control the size and composition of NPCs.
Professor Kim’s team used Zinc Finger, a DNA binding protein, to develop a NPCs manufacturing technique to create clusters of the desired size easily. The Zinc Finger protein contains a zinc ion and specifically recognizes DNA sequence upon binding, which allows the exquisite control of the size and the cluster composition. The technique is also bio-friendly.
Professor Kim’s team created linear structure of different sizes of NPCs using Zinc Finger proteins and three DNA sequences of different lengths. The NPCs they produced confirmed their ability to control the size and structure of the cluster by using different DNA lengths.
The NPCs showed tripled T2 relaxation rates compared to the existing MRI contrast media (Feridex) and effectively transported to targeted cells. The research findings show the potential use of NPCs in biological and medical fields such as MRI contrast media, fluorescence imaging, and drug transport.
The research used the specific binding property of protein and DNA to develop a new method to create an inorganic nanoparticle’s supramolecular assembly. The technique can be used and applied extensively in other nanoparticles for future research in diagnosis, imaging, and drug and gene delivery.
Figure 1. A Mimetic Diagram of NPCs Manufacturing Technique Using DNA Binding Protein Zinc Finger
Figure 2. Transmission Electron Microscopy Images showing different sizes of NPCs depending on the length of the DNA
2014.12.04 View 13044