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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 12460 -
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 9989 -
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 6331 -
Broadband and Ultrathin Polarization Manipulators Developed
Professor Bumki Min from the Department of Mechanical Engineering at KAIST has developed a technology that can manipulate a polarized light in broadband operation with the use of a metamaterial.
It is expected that this technology will lead to the development of broadband optical devices that can be applied to broadband communication and display.
When an object or its structure is analyzed by using a polarized light such as a laser, the results are generally affected by the polarized state of the light. Therefore, in an optics laboratory, the light is polarized by various methods.
In such cases, researchers employ wave plates or photoactive materials. However, the performance of these devices depend vastly on wavelength, and so they are not suitable to be used as a polarizer, especially in broadband.
There were many attempts to make artificial materials that are very photoactive by using metamaterials which have a strong resonance. Nonetheless, because the materials had an unavoidable dispersion in the resonance frequency, they were not adequate for broadband operation.
Professor Min’s research team arranged and connected helical metamaterials that are smaller than the wavelength of light. They verified theoretically and experimentally that polarized light can be constantly rotated regardless of the wavelength by super-thin materials that have thickness less than one-tenth of the wavelength of the light. The experiment which confirmed the theory was conducted in the microwave band.
Broadband polarized rotational 3D metamaterials were found to rotate the polarized microwave within the range of 0.1 GHz to 40 GHz by 45 degrees regardless of its frequency. This nondispersive property is quite unnatural because it is difficult to find a material that does not change in a wide band.
In addition, the research team materialized the broadband nondispersive polarized rotational property by designing the metamaterial in a way that it has chirality, which determines the number of rotations proportional to the wavelength.
Professor Min said, “As the technology is able to manipulate ultrathin polarization of light in broadband, it will lead to the creation of ultra-shallow broadband optical devices.”
Sponsored by the Ministry of Science, ICT and Future Planning of the Republic of Korea and the National Research Foundation of Korea, this research was led by a PhD candidate, Hyun-Sung Park, under the guidance of Professor Min. The research findings were published online in the November 17th issue of Nature Communications.
Figure 1 – Broadband and Ultrathin Polarization Manipulators Produced by 3D Printer
Figure 2 – Concept of Broadband and Ultrathin Polarization Manipulators
2014.12.03 View 10639 -
Structure of Neuron-Connecting Synaptic Adhesion Molecules Discovered
A research team has found the three-dimensional structure of synaptic adhesion molecules, which orchestrate synaptogenesis. The research findings also propose the mechanism of synapses in its initial formation. Some brain diseases such as obsessive compulsive disorder (OCD) or bipolar disorders arise from a malfunction of synapses. The team expects the findings to be applied in investigating pathogenesis and developing medicines for such diseases.
The research was conducted by a Master’s candidate Kee Hun Kim, Professor Ji Won Um from Yonsei University, and Professor Beom Seok Park from Eulji University under the guidance of Professor Homin Kim from the Graduate School of Medical Science and Engineering, KAIST, and Professor Jaewon Ko from Yonsei University. Sponsored by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, the research findings were published online in the November 14th issue of Nature Communications.
A protein that exists in the neuronal transmembrane, Slitrk, interacts with the presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) and forms a protein complex. It is involved in the development of synapses in the initial stage, and balances excitatory and inhibitory signals of neurons.
It is known that a disorder in those two proteins cause a malfunction of synapses, resulting in neuropsychosis such as autism, epilepsy, OCD, and bipolar disorders. However, because the structure as well as synaptogenic function of these proteins were not understood, the development of cures could not progress.
The research team discovered the three-dimensional structure of two synaptic adhesion molecules like Slitrk and LAR-RPTPs and identified the regions of interaction through protein crystallography and transmission electron microscopy (TEM). Furthermore, they found that the formation of the synapse is induced after the combination of two synaptic adhesion molecules develops a cluster.
Professor Kim said, “The research findings will serve as a basis of understanding the pathogenesis of brain diseases which arises from a malfunction of synaptic adhesion molecules. In particular, this is a good example in which collaboration between structural biology and neurobiology has led to a fruitful result.” Professor Ko commented that “this will give new directions to synaptic formation-related-researches by revealing the molecular mechanism of synaptic adhesion molecules.”
Figure 1: Overview of the PTPd Ig1–3/Slitrk1 LRR1 complex.
Figure 2: Representative negative-stained electron microscopy images of Slitrk1 Full ectodomain (yellow arrows indicate the horseshoe-shaped LRR domains). The typical horseshoe-shaped structures and the randomness of the relative positions of each LRR domain can be observed from the two-dimensional class averages displayed in the orange box.
Figure 3: Model of the two-step presynaptic differentiation process mediated by the biding of Slitrks to LAR-RPTPs and subsequent lateral assembly of trans-synaptic LAR-RPTPs/Slitrik complexes.
2014.11.28 View 11053 -
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 8276 -
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 10621 -
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 8375 -
The Hancom and KAIST Research Center Opens
KAIST and Hancom, Inc., an office suite developer in Korea, established a joint research center to develop software technology and its related industry. President Steve Kang of KAIST, Sang-Chul Kim, the Chief Executive Officer (CEO) of Hancom, and professors from the computer science department at KAIST attended a ceremony to celebrate the opening of the center.
KAIST and Hancom signed a memorandum of understanding in April this year for the development of software industry in Korea, and based on the agreement, the two institutions identified five research projects and created a research center to implement them effectively.
President Kang said, “I hope that the research center will serve as a good example of university and industry collaboration. To that end, we will provide our support to the maximum extent possible to lead the software industry in Korea. We are also planning to hold a joint workshop on the latest trends in software technology and on the education of software developers.”
Established in 1990, Hancom created the native word processor for the Korean language called “Hangul.”
2014.11.05 View 7527 -
Parents of Alumni Donates to KAIST
Parents of KAIST alumni donated a scholarship of USD 4,800 to the university. A donation ceremony took place at the president’s office on October 21, 2014.
Two sons and the daughter-in-law of Ki-Hong Oh (husband) and Soon-Yi Kim (wife) studied at KAIST. Hwan-Hee Oh and Hwan-Yup Oh graduated with Master’s degrees in Mechanical Engineering in 2005 and 2009, respectively. Jung-Im Min received a Ph.D. in Mechanical Engineering in 2005.
Oh and Kim, who are orange growers in Jeju Island, Korea, said, “We have always appreciated the generous support our children received from KAIST and thought for many years about ways to make a contribution to the development of the university. Although this is a small amount, we are pleased to express our appreciation to KAIST.”
The couple hope that their donation will inspire others in Korea to follow suit and added, “Just like many of the great universities in the west which are supported through donations made by their alumni and people from all walks of life, we would like to see Korean universities also benefit from such a culture and practice.”
President Steve Kang expressed his gratitude to the couple and said, “KAIST will cherish your philanthropic good deeds, and the scholarship will be used to support students as you wish.”
2014.10.22 View 7946 -
KAIST and Samsung Heavy Industries Celebrate 20 Years of Cooperation
KAIST and Samsung Heavy Industries (SHI) celebrated the twentieth anniversary of their university-industry cooperation in shipbuilding and ocean technology research. Established in 1995, the cooperation has remained steadfast for two decades, even times when Korea suffered gravely from its financial crisis in late 1990s.
A ceremony to commemorate the cooperation took place at the Mechanical Engineering Building on October 17, 2014. About thirty distinguished guests including the Head of the Department of Mechanical Engineering, Professor Choong-Sik Bae, and the chief engineer of SHI Marine Research Institute, Dr. Jong-Soo Seo, participated in the ceremony.
The cooperation programs included appointing advisory professors for technological support, implementing business-based academic courses, offering university-industry wide open lectures, opening regular courses for auditing, and finding possible joint researches. Through this cooperation, Samsung has secured technologies needed for industry, and KAIST has produced students who have real-world experience in industrial fields.
Twenty years of cooperation has produced shining results by running various programs such as technological advice, special lectures, small-scale research projects, consignment research projects, and courses for research and design personnel.
For example, what started as a small-scale research project with USD 4,800 in funding, the LNG (Liquefied Natural Gas) related research has grown into a large-scale research project with a total of USD 2.85 million in funding. As a result, they developed a secondary barrier for LNG carriers which was recognized by Lloyd‘s Register. Their research eventually lowered ship manufacturing costs tremendously.
In 2003, the cooperation project received the presidential citation from the University-Industry Cooperation Competition organized by the Federation of Korean Industries.
KAIST and SHI planned to increase their cooperation to make it Korea’s leading university-industry cooperation program.
Professor Bae said, “Our programs to focus on solving industrial problems have turned out quite successful.” He emphasized that “for this reason, the cooperation even continued during the Asian financial crisis in 1997.”
He added, “By expanding the current cooperation, we aim to make it an exemplary program that contributes to Korea’s shipbuilding and ocean plant industries.”
2014.10.21 View 9200 -
Wuhan University, China, Appoints Distinguished Professor Sang Yup Lee as Honorary Professor
Sang Yup Lee, Distinguished Professor of the Department of Chemical and Biomolecular Engineering at KAIST, has been appointed an honorary professor at Wuhan University in Hubei Province, China. This is the third time that Professor Lee has received an honorary professorship from Chinese academic institutions. The Chinese Academy of Sciences appointed him an honorary professor in 2012, and Shanghai Jia Tong University asked him to serve as an advisory professor in 2013, respectively.
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 the Chairman of the Future of Chemicals, Advanced Materials & Biotechnology, Global Agenda Councils, WEF.
Wuhan University is a comprehensive and key national university selected by the Chinese government as a major recipient of state funding for research. It is also known as one of the most beautiful campuses in China.
2014.10.20 View 8714