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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 13609 -
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 10985 -
IamCompany and KAIST's Midam Scholarship Contribute Scholarship to High School Students
IamCompany, a venture company established by a KAIST student which provides mobile users with educational applications, and Midam Scholarship, a volunteer group consisting of KAIST students that helps junior and high school students study math and science, selected a total of 118 students and presented them with scholarships.
Among the students, Ki-Bum Kim of Kyung-Hee High School in Seoul received USD 1,300, the largest sum.
In-Mo Chung, the President of IamCompany, who once worked as a member of Midam Scholarship, said, “I joined this scholarship program to support the Midam Scholarhsip which offers educational services to less privileged students. I hope many young students will benefit from this and receive an equal opportunity for better education.”
2014.12.15 View 6622 -
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 11589 -
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 13062 -
Elsevier Selects a KAIST Graduate's Paper as the Top Cited Papers in 2011-2012
Dr. Myung-Won Seo, a graduate from the Department of Chemical and Bimolecular Engineering at KAIST, published a paper in January 2011 in Chemical Engineering Journal, which was entitled “Solid Circulation and Loop-seal Characteristics of a Dual Circulating Fluidized Bed: Experiments and CFD Simulation.” His paper was selected by Elsevier as the Top Cited Papers of 2011-2012. The Chemical Engineering Journal is a renowned peer-reviewed journal issued by Elsevier.
Dr. Seo published another paper, “CFD Simulation with Experiments in a Dual Circulating Fluidized Bed Gasifier,” in January 2012 in Computers & Chemical Engineering, which was also selected as the Most Downloaded Papers in 2012-2013.
Dr. Seo graduated with a doctoral degree from KAIST in 2011. He is currently working at the Clean Fuel Laboratory, the Korea Institute of Energy Research, Daejeon, as a researcher. His research areas are coal gasification, upgrading, and liquefaction, as well as energy and chemical production from low-grade fuels such as biomass and wastes.
2014.11.24 View 9749 -
The 2014 Wearable Computer Competition Takes Place at KAIST
“This is a smart wig for patients who are reluctant to go outdoors because their hair is falling out from cancer treatment.”
A graduate student from Sungkyunkwan University, Jee-Hoon Lee enthusiastically explains his project at the KAIST KI Building where the 2014 Wearable Computer Competition was held. He said, “The sensor embedded inside the wig monitors the heart rate and the body temperature, and during an emergency, the device warns the patient about the situation. The product emphasizes two aspects; it notifies the patient in emergency situations, and it encourages patients to perform outdoor activities by enhancing their looks.”
The the tenth anniversary meeting of the 2014 Wearable Computer Competition took place at the KAIST campus on November 13-14, 2014.
A wearable computer is a mobile device designed to be put on the body or clothes so that a user can comfortably use it while walking. Recently, these devices that are able to support versatile internet-based services through smartphones are receiving a great deal of attention.
Wearable devices have been employed in two categorizes: health checks and information-entertainment. In this year’s competition, six healthcare products and nine information-entertainment products were exhibited.
Among these products, participants favored a smart helmet for motorcycle drivers. The driver can see through a rear camera with a navigation screen of the smartphone and text messages through the screen installed in the front glass of the helmet. Another product included a uniform that can control presentation slides by means of motion detection and voice recognition technology. Yet another popular device offered an insole to guide travelers to their destination with the help of motion sensors.
The chairman of the competition, Professor Hoi-Jun Yoo from the Department of Electrical Engineering at KAIST said, “Wearable devices such as smart watches, glasses, and clothes are gaining interest these days. Through this event, people will have a chance to look at the creativity of our students through the display of their wearable devices. In turn, these devices will advance computer technology.”
The third annual wearable computer workshop on convergence technology of wearable computers followed the competition. In the workshop, experts from leading information technology companies such as Samsung Electronics, LG Electronics, and KT Corporation addressed the convergence technology of wearable computers and trends in the field.
2014.11.19 View 10483 -
3D Printer Developed by KAIST Undergraduate Students
More than 100 Pre-orders Prior to Product Launch Made
KAIST undergraduate students received more than 100 pre-orders before the launch for 3D printers they developed and became a hot topic of interest.
KAIST Research Institute for Social Technology and Innovations (Head Hong-Kyu Lee) had a launch party at Daejeon Riviera Hotel on 17 November 2014 for “Commercial Delta 3D Printer” developed by KAIST undergraduate students inviting around 50 businesses, buyers and representatives of 3D Printing Industry Association.
“3D Printer” uses blueprints of products such as toys, mug cups and chairs to make 3D objects and is thought to be revolutionary technology in manufacturing industry. The interest has grown as recent printers could print even fruits and cosmetics.
The printing structure of 3D printer can be divided roughly into horizontal Mendel method and Delta method. KAIST students focused on the Delta method to give a differentiated product from 90% of commercial products that use Mendel method.
First, the students focused on lowering the cost of unit price by using self-developed components. The carriage (transport machine) of the product is replaced by self-developed components instead of bearing to reduce the noise and the linking method was changed to beads from loop guide to increase the completeness of the printed product. Also, an auto-levelling is loaded to ensure the nozzle and the bed is parallel and hence increasing convenience for the users. Further, the printer, designed by a product designer in Germany, is linked to a smartphone application for blueprints.
A student in the development team, Seokhyeon Seo (Department of Computer Science, 3rd Year Undergraduate) said, “The biggest merits of the product are lowering the price to a 1/3 by using self-developed components and reducing the noise.” He continued, “By using a smartphone application, anyone can easily design the product. So it is applicable to use for education or at home”
In the exhibit, “3D Printing Korea 2014,” in Coex, Seoul the printer had a preview demonstration, and received more than 100 pre-orders from educational and business training institutions. Further, buyers from Canada and the US requested opening agencies in their countries.
KAIST Research Institute for Social Technology and Innovations Head Hong-Kyu Lee said, “3D printing is an innovative technology that could bring the 3rd industrial revolution.” He continued, “It is still early days but the demand will increase exponentially.”
This project was a research project of KAIST Research Institute for Social Technology and Innovations led by a development team consisting of 4 undergraduate students of KAIST, one student from University of Oxford and one German product designer.
Students in the picture below are Won-Hoi Kim (Department of Mechanical Engineering), Sung-Hyun Cho (Department of Mechanical Engineering), and Suk-Hyun Seo (Department of Computer Science) from left to right.
2014.11.19 View 11034 -
Eggshell-like Cell Encapsulation and Degradation Technology Developed
Some bacteria form endospores on cell walls to protect their DNA in case of nutrient deficiency. When an endospore meets a suitable environment for survival, the cell can revert to the original state from which it can reproduce.
The technique that can artificially control such phenomenon was developed by an international team of researchers. At first, a cell is wrapped and preserved like an egg. When the cell is needed, the technique allows the endospore to decompose while it is alive. Future applications for this technique include cell-based biosensor, cell therapy, and biocatalyst processes.
Professors Insung Choi and Younghoon Lee from the Department of Chemistry at KAIST as well as and Professor Frank Caruso from the University of Melbourne developed this technique which permits a cell to stay alive by coating it with film on a nanometer scale and then to be decomposed while it is alive.
The research finding was published in the November 10th issue of Angewandte Chemie International Edition as the lead article.
Cell encapsulation allows researchers to capture a cell in a tight capsule while it is alive. It is highly recognized in cell-based applications where the control of cell stability and cell-division is the biggest issue.
Traditional cell encapsulation methods utilized organic film or inorganic capsules that are made of organic film moldings. Although these films tightly closed around the cell, because they were not easily decomposable, it was difficult to apply the method.
The research team succeeded in encapsulating each cell in a metal-polyphenol film by mixing tannic acid and iron ion solution with yeast cells.
Usually extracted from oak barks or grape peels, tannic acid is a natural substance. It forms a metal-polyphenol film within ten seconds when it meets iron ions due to its high affinity with cells. Cells encapsulated with this film presented high survival rates. Since the film forms quickly in a simple manner, it was possible to obtain large amount of encapsulated cells.
The research team also found that the metal-polyphenol film was stable in neutral pH, but is easily degradable under a weak acidic condition. Using this property, they were able to control cell division by restoring the cell to its pre-encapsulated state at a desired moment.
Protecting the cell from the external environment like an egg shell, the metal-polyphenol film protected the cell against foreign conditions such as lytic enzymes, extended exposure to UV radiation, and silver nanoparticles. The research indicated that the encapsulated cells had a high survival rate even under extreme environments.
Professor Lee said that “not only the cells remain alive during the encapsulation stage, but also they can be protected under extreme environment.” He added, “This is an advanced cell encapsulation technology that allows controlling cell-division of those cells through responsive shell degradation on-demand.”
Professor Choi commented, “Although the cell encapsulation technology is still in its infancy, as the technology matures the application of cell-manipulation technology will be actualized.” He highlighted that “it will serve as a breakthrough to problems faced by cell-based applications.”
Sponsored by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, the research was led by two Master’s candidates, Ji Hun Park and Kyung Hwan Kim, under the joint guidance of research professors from KAIST and the University of Melbourne.
Figure 1: Lead article of Angewandte Chemie
Background: Shows a live native yeast (in green) encapsulated in a metal-polyphenol film (in red) illustrating the vitality of the yeast
Front: A native yeast at each encapsulation stage
Pictured on the bottom left is a cell prior to encapsulation. Following the red arrow, the native yeast is in purple to show metal-polyphenol film formed around the cell. The cell after the green arrow is a visualization of the degradation of the film in weak acidic condition.
Figure 2: A mimetic diagram of cell encapsulation with a metal-polyphenol film
Top: A native yeast before encapsulation
Middle: A native yeast encapsulated with Tannic Acid-Fe (III) Nanoshell – cell-division of the encapsulated cell is controlled by pH and the shell is protected against silver nanoparticle, lytic enzyme, and UV-C
Bottom: Shell degradation on-demand depending on pH
2014.11.18 View 10411 -
The Website of the KAIST Industrial Design Department Receives a Design Award
The 10th QS-Apple Higher Education Conference and Exhibition took place on November 11-13, 2014 in Taipei, Taiwan. The conference was hosted by Quacquarelli Symonds, a British company specializing in education, which publishes annually its world university rankings. Apple stands for Asia Pacific Professional Leaders in Education.
The QS-Apple conference supports the internationalization of Asia Pacific universities by providing opportunities for networking, exchanging best practices, and discussing recent developments in higher education. During the conference, the organizers presented the Creative Awards for best international education promotional designs in four categories: Website Pages, Video, Print Advertisement, and International Student Recruitment Brochures.
KAIST’s Industrial Design Department received the Best Website Pages Award for their website in recognition of high levels of user convenience and satisfaction as well as English language services. A total of 39 universities in the Asia and Pacific region competed in this category, and Nanyang Technological University in Singapore came in second place, followed by Hong Kong Baptist University in third.
2014.11.13 View 8992 -
Distinguished Professor Sang Yup Lee Accepts an Honorary Professorship at Beijing University of Chemical Technology
Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed an honorary professor at Beijing University of Chemical Technology (BUCT). Founded in 1958, BUCT is one of the outstanding universities in mainland China, especially in chemistry studies.
In addition to the Chinese Academy of Sciences (2012), Shanghai Jiao Tong University (2013), Wuhan University (2014), and Hebei University of Technology (2014), this is the fifth honorary professorship Professor Lee has received from higher education institutions in China.
Professor Lee was recognized for his pioneering research in systems metabolic engineering of microorganisms necessary for the development of green chemical industries. He succeeded in producing succinic acid through bacterial fermentation and engineering plastic raw materials in the most effective and economical method for the first time in the world. Professor Lee also developed polylactic acid, a bio-based polymer that allows plastics to be produced through natural and renewable resources, as well as the microbial production of alkanes, an alternative to gasoline that can be produced from fatty acids.
Professor Lee has been actively working as a member of a group of global leaders supported by the World Economic Forum (WEF), serving as the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF.
2014.11.13 View 11677 -
President Steve Kang will serve as the Chairman of Global Agenda Council on the Future of Electronics of the World Economic Forum
President Steve Kang of KAIST has been appointed to the Chairman of the Global Agenda Council (GAC) on the Future of Electronics of the World Economic Forum (WEF). He will serve the position for two years until September 2016.
President Kang and WEF council members co-hosted, with the government of the United Arab Emirates (UAE), the Future Circles Initiative, a future-focused, innovative brainstorming conference to help find strategies and ideas for the development of UAE. The conference took place on November 11-12, 2014 at the Mina Al Salam Hotel in Dubai.
WEF has about 80 GACs. Each council consists of 15 experts and thought leaders from the academia, industry, government, business, and non-profit sector and deals with specific issues that are important and relevant to the global community such as ageing, artificial intelligence and robotics, brain research, food and nutrition security, education, social media, and future of chemicals, advanced materials and biotechnology.
President Kang was recognized for his contribution to the advancement of science and higher education as an engineer, scholar, and professor. He led the development of the world’s premier CMOS 32-bit microprocessors while working at the AT&T Bell Laboratories. He also taught and conducted research at the University of California, Santa Cruz, and the University of Illinois, Urbana-Champaign. President Kang served as the chancellor of the University of California at Merced from March 2007 to June 2011.
2014.11.11 View 9242