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Key Interaction between the Circadian Clock and Cancer Identified
Professor Jae Kyoung Kim and his research team from the Department of Mathematical Sciences at KAIST found that the circadian clock drives changes in circadian rhythms of p53 which functions as a tumor suppressor. Using a differential equation, he applied a model-driven mathematical approach to learn the mechanism and role of p53.
Kim’s mathematical modeling has been validated by experimental studies conducted by a research team at Virginia Polytechnic Institute and State University (Virginia Tech) in the United State, which is led by Professor Carla Finkielstein. As a result, the researchers revealed that there is an important link existed between the circadian clock and cancer.
The findings of this research were published online in Proceedings of the National Academy of Sciences of the United States of the America (PNAS) on November 9, 2016.
The circadian clock in our brain controls behavioral and physiological processes within a period of 24 hours, including making us fall asleep at a certain time by triggering the release of the sleep hormone melatonin in our brain, for example, around 9 pm. The clock is also involved in various physiological processes such as cell division, movement, and development.
Disruptions caused by the mismatch of the circadian clock and real time due to chronic late night work, shiftwork, and other similar issues may lead to various diseases such as diabetes, cancer, and heart disease.
In 2014, when Kim met with Finkielstein, her research team succeeded in observing the changes of p53 over a period of 24 hours, but could not understand how the circadian clock controls the 24-hour rhythm of p53. It was difficult to determine p53’s mechanism since its cell regulation system is far more complex than other cells
To solve the problem, Kim set up a computer simulation using mathematical modeling and ran millions of simulations. Instead of the traditional method based on trial and error experiments, mathematical modeling allowed to save a great deal of time, cost, and manpower.
During this process, Kim proved that the biorhythm of p53 and Period2, an important protein in the circadian clock, are closely related. Cells usually consist of a cell nucleus and cytoplasm. While p53 exists in both nucleus and cytoplasm, it becomes more stable and its degradation slows down when it is in the nucleus.
Kim predicted that the Period2 protein, which plays a key role in the functioning of the circadian clock, could influence the nucleus entry of the p53 protein.
Kim’s predictions based on mathematical modeling have been validated by the Virginia team, thereby revealing a strong connection between the circadian clock and cancer.
Researchers said that this research will help explain the cause of different results from numerous anticancer drugs, which are used to normalize the level of p53, when they are administrated at different times and find the most effective dosing times for the drugs.
They also believe that this study will play an important role in identifying the cause of increasing cancer rates in shift-workers whose circadian clocks are unstable and will contribute to the development of more effective treatments for cancer.
Professor Kim said, “This is an exciting thing that my research can contribute to improving the healthy lives of nurses, police officers, firefighters, and the like, who work in shifts against their circadian rhythms. Taking these findings as an opportunity, I hope to see more active interchanges of ideas between biological sciences and mathematical science in Korea.”
This research has been jointly conducted between KAIST and Virginia Tech and supported by the T. J. Park Science Fellowship of POSCO, the National Science Foundation of the United States, and the Young Researcher Program of the National Research Foundation of Korea.
Picture 1. The complex interaction between tumor antigen p53 and Period2 (Per2) which plays a major role in the circadian clock as revealed by mathematical simulations and experiments
Picture 2. A portion of the mathematical model used in the research
Picture 3. Professor Jae Kyoung Kim (third from left) and the Virginia Tech Research Team
2016.11.17 View 7002 -
KAIST Ranks Third in the World's Top Universities for Attracting Industry Funding
The Times Higher Education released its World University Rankings online, naming the 20 best institutions that secured the largest amount of research funding from the private sector, on March 8, 2016.
The rankings were based on the 2013 record of industry-sector investments made per academic of an institution.
According to the list, KAIST ranked third with a figure of $254,700.
Germany’s Ludwig Maximilian University (Munich) took first place ($400,000), while the United State’s Duke University placed second ($290,000).
For a full list of the rankings, go to https://www.timeshighereducation.com/world-university-rankings/funding-for-innovation-ranking-2016.
2016.03.08 View 3633 -
KAIST's Mathematician Reveals the Mechanism for Sustaining Biological Rhythms
Our bodies have a variety of biological clocks that follow rhythms or oscillations with periods ranging from seconds to days. For example, our hearts beat every second, and cells divide periodically. The circadian clock located in the hypothalamus generates twenty-four hour rhythms, timing our sleep and hormone release. How do these biological clocks or circuits generate and sustain the stable rhythms that are essential to life?
Jae Kyoung Kim, who is an assistant professor in the Department of Mathematical Sciences at KAIST, has predicted how these biological circuits generate rhythms and control their robustness, utilizing mathematical modeling based on differential equations and stochastic parameter sampling. Based on his prediction, using synthetic biology, a research team headed by Matthew Bennett of Rice University constructed a novel biological circuit that spans two genetically engineered strains of bacteria, one serves as an activator and the other as a repressor to regulate gene expression across multiple cell types, and found that the circuit generates surprisingly robust rhythms under various conditions.
The results of the research conducted in collaboration with KAIST (Korea Institute of Science and Technology), Rice University, and the University of Houston were published in Science (August 28, 2015 issue). The title of the paper is "Emergent Genetic Oscillations in a Synthetic Microbial Consortium" .
The top-down research approach, which focuses on identifying the components of biological circuits, limits our understanding of the mechanisms in which the circuits generate rhythms. Synthetic biology, a rapidly growing field at the interface of biosciences and engineering, however, uses a bottom-up approach.
Synthetic biologists can create complex circuits out of simpler components, and some of these new genetic circuits are capable of fluctuation to regulate gene production. In the same way that electrical engineers understand how an electrical circuit works as they construct batteries, resistors, and wires, synthetic biologists can understand better about biological circuits if they put them together using genes and proteins. However, due to the complexity of biological systems, both experiments and mathematical modeling need to be applied hand in hand to design these biological circuits and understand their function.
In this research, an interdisciplinary approach proved that a synthetic intercellular singling circuit generates robust rhythms to create a cooperative microbial system. Specifically, Kim's mathematical analysis suggested, and experiments confirmed, that the presence of negative feedback loops in addition to a core transcriptional negative feedback loop can explain the robustness of rhythms in this system. This result provides important clues about the fundamental mechanism of robust rhythm generation in biological systems.
Furthermore, rather than constructing the entire circuit inside a single bacterial strain, the circuit was split among two strains of Escherichia coli bacterium. When the strains were grown together, the bacteria exchanged information, completing the circuit. Thus, this research also shows how, by regulating individual cells within the system, complex biological systems can be controlled, which in turn influences each other (e.g., the gut microbiome in humans).
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Ye Chen, a graduate student in Bennett's laboratory at Rice University, and Jae Kyoung Kim, an assistant professor at KAIST and a former postdoctoral fellow at Ohio State University, are the lead authors of the paper. The co-authors are Rice graduate student Andrew Hirning and Krešimir Josic?, a professor of mathematics at the University of Houston. Bennett is the Assistant Professor of the Biochemistry and Cell Biology Department at Rice University.
About the researcher: While Jae Kyoung Kim is a mathematician, he has also solved various biological puzzles in collaboration with various experimental laboratories of Matthew Bennett at Rice University, David Virshup at Duke and the National University of Singapore, Carla Finkielstein at Virginia Polytechnic Institute and State University, Choo-Gon Lee at the Florida State University, Seung-Hee Yoo at the Medical School of the University of Texas, Toru Takumi at RIKEN Brain Science Institute, and Travis Wager at Pfizer Inc. He has used non-linear dynamics and stochastic analysis to understand the function of biochemical networks in biological systems. In particular, he is interested in mechanisms generating and regulating biological rhythms.
Picture 1: This schematic image is the design of a biological circuit between two strains of bacteria and the part of differential equations used to understand the function of the biological circuit.
Picture 2: The core transcriptional negative feedback loop and additional negative feedback loop in the biological circuit (picture 1) generate robust rhythms. The snapshots correspond the red dots in the time series graph.
2015.08.31 View 8213 -
KAIST Ranks 26th in Engineering & Technology and 52nd overall in the Times Higher Education World University Rankings 2014-2015
The 2014-2015 Times Higher Education (THE) World University Rankings were released on October 1, 2014. KAIST took 52nd place in the overall rankings and 26th in the field of engineering and technology.
THE used 13 performance indicators to evaluate universities, grouping them into five areas of teaching, research, citations, industry income, and international outlook.
In recent years, KAIST has seen steady improvements in areas of research, citations, and international outlook. In addition to KAIST, two Korean universities, Seoul National University (50th) and Pohang University of Science and Technology (66th), were included within the top 100 universities.
For details, please visit:
http://www.timeshighereducation.co.uk/world-university-rankings/2014-15/world-ranking.
2014.10.03 View 8006 -
KAIST's Artist Residency Program Recruits Third Round Applicants
KAIST is accepting applications for the third Artist Residency Program, “The Endless Road,” from September 22, 2014 to October 21, 2014.
Through the program, KAIST has supported emerging and promising artists, writers in particular, such as novelists, poets, storytellers, and playwrights, to live on the campus and encourage them to interact with students and faculty. Originally initiated to integrate art and science and to seek synergistic effects that benefit both communities, the program has been well received by artists and scientists.
A total of three writers will be selected, and they will receive a stipend of USD 753.00 per month for six months. The program is available only in Korean.
2014.10.01 View 5852 -
KAIST and the National Assembly of Korea Create a Committee to Plan "Patent Hub Korea"
The KAIST Graduate School of Future Strategy (GSFS) and the National Assembly of the Republic of Korea held a meeting at the National Assembly building in Seoul on September 23, 2014.
At the meeting, the two organizations agreed to create a planning committee that will work for the construction of Korea as a global patent hub. In addition, the two also reviewed national laws and regulations related to patents and intellectual property rights (IPR) and discussed a future action agenda.
Dean Kwang-Hyung Lee of GSFS, Chairman Ui-Hwa Chung of the National Assembly, Chairman Jong-Yong Yoon of the Presidential Council on Intellectual Property, and many representatives from the academia, government, and law participated in the meeting.
Dean Lee, who is the co-chairman of the planning committee, said:
“Although Korea has globally ranked number five in patents and IPR, it still suffers from the lack of relevant legal systems and professionals. I hope that the planning committee will serve as a catalyst to make Korea stronger in the field of intellectual property and to accelerate the creation of the Patent Hub Korea.”
2014.09.24 View 7324 -
Times Higher Education magazine features KAIST, July 2014
The Times Higher Education (THE) has featured KAIST in an article entitled “Young Universities’ Secrets of Success” dated on July 17, 2014.
The magazine chose five universities from the Times Higher Education's 100 Under 50 2014 rankings: KAIST, Koç University in Turkey, Maastricht University in Netherlands, Nanyang Technological University in Singapore, and Hong Kong Polytechnic University, China. These universities are less than 50 years old.
The article highlighted some of their current efforts to deliver quality administrative service for students and professors as well as innovative education and research programs to set them apart from long-established elite universities such as Harvard and Cambridge.
For the full text, please visit the link below:
Times Higher Education, July 17, 2014
“Young Universities’ Secret of Success”
http://www.kaist.ac.kr/Upl/downfile/THE's_Article_Jul_17_2014.pdf
2014.07.23 View 6695 -
2014 Conference on Korean Sociology Held at KAIST
The Korean Sociological Association (KSA) hosted a two-day conference in 2014 entitled “In the age of anxiety, sociology can present answers” at the College of Liberal Arts and Convergence Science, KAIST, on June 20-21, 2014. Professor Jung-Ro Yoon of the Department of Humanities and Social Sciences at KAIST is the President of KSA. The conference addressed issues such as big data and risk society. During the conference, 40 sessions took place, and 150 research papers were released.
Professor Yoon said, “The conference will offer a great opportunity for Korean sociologists to discuss anxiety, chaos, risk, and the uncertainty that Korean society experiences and suggest answers and a new vision upon which Korean society should move forward.”
2014.06.22 View 7486 -
A KAIST graduate named one of seven Microsoft Research Faculty Fellows for 2014
Yong-Yeol Ahn, a professor of the School of Informatics and Computing, Indiana University Bloomington (IUB), has been selected as one of the seven winners for the Microsoft Research Faculty Fellowship 2014. He received his Ph.D. in 2008 from KAIST.
Each year, since 2005, Microsoft Research has recognized innovative, promising new faculty members in computer science from a number of research institutions to join the ranks of Microsoft Research Faculty Fellows. The winners are awarded $200,000 grants to further advance their research.
For details, below please see a press release issued by IUB on June 12, 2014.
IU Bloomington Newsroom
Press Release, June 12, 2014
IU informaticist Y.Y. Ahn named one of seven Microsoft Research Faculty Fellows
http://news.indiana.edu/releases/iu/2014/06/yy-ahn-microsoft-research-faculty-fellow.shtml
2014.06.15 View 7602 -
2013 International Forum on Eco-Friendly Vehicle and System
Leaders in transportation technology gathered at KAIST to discuss commercialization & standardization and to encourage the exchange of research progress, strategy, and future initiatives in transportation technology.
The Graduate School for Green Transportation at KAIST hosted the 2013 International Forum on Eco-friendly Vehicles and Systems (IFEV) in Fusion Hall of the KAIST Institute Building from October 21 to 22.
About 50 leaders in the field of future transportation from academic institutes and industries including Dr. Soon-Man Hong, President of Korea Railroad Research Institute (KRRI), Dr. Kwang-Hee Nam, Professor at Pohang University of Science and Technology (POSTECH), and Mr. Mike Schagrin, the Intelligent Transportation Systems Program Manager of the US Department of Transportation (retired) participated in the 4th annual IFEV.
The commercialization & standardization session and a technical session were followed by the plenary meeting of the forum.
Dr. Hong, the keynote speaker, introduced the High Capacity Double Deck High Speed Train, Near Surface Subway System, and Urban Railway System with Wireless Power Transfer Technology under the title “Korea’s Policy and Technology Initiative for Enhancing Green Transport Systems.”
Dr. Kwang-Hee Nam presented “Electric Vehicle Trends & the POSTECH E-Car Research Center Power Train Design,” followed by Mr. Mike Schagrin who spoke about “Going Green with Connected Automation.”
Dr. Omer C. Onar from the Oak Ridge National Laboratory (ORNL) shared recent research on “ORNL Development in Stationary and Dynamic Wireless Charging.”
In the commercialization session, Faical Turki of Vahle, Germany, presented “Wireless Inductive Battery Chargers,” and Professor Kazuyuki Ouchi from Tokyo University presented “Wind Challenger, the Next Generation Hybrid Vessels.”
In the technical session, presentations and discussions were performed on future ground vehicles and railroad technology, intelligent transportation systems and strategy, and policy on eco-friendly vehicle technology, including Professor In-Soo Suh of the Graduate School for Green Transportation at KAIST who presented on “Armadillo-T: 4WD Micro Electric EV with a Foldable Body Concept.”
On the second day of IFEV 2013, representatives of the European Union’s Safe and Green Road Vehicles (SAGE) consortium discussed connectivity in road transportation as a means of improving safety, efficiency and convenience in future safe and green vehicles with collaboration from Korean transportation organizations such as the Korea Transport Institute and Electronics and Telecommunications Research Institute.
Professor Suh, who organized the forum, said, “This forum will serve as an excellent opportunity to discuss and share R&BD progress in the green transportation field. “Details can be found at http://gt.kaist.ac.kr/ifev2013/.
2013.11.15 View 11133 -
KAIST unveils foldable micro electric car, Armadillo-T
The small and light electric car completely folds in half when parking, making it a perfect fit for public or private transportation in an urban environment.
Looking for a parking space for hours at a busy shopping mall or being stuck on roads jammed with cars releasing large amounts of carbon dioxide are all-too-familiar scenes for city dwellers.
A group of researchers at the Korea Advanced Institute of Science and Technology (KAIST) recently developed a possible solution to such problems: a foldable, compact electric vehicle that can be utilized either as a personal car or part of the public transit system to connect major transportation routes within a city.
In-Soo Suh, associate professor of the Graduate School for Green Transportation at KAIST, and his research team introduced a prototype micro electric car called "Armadillo-T," whose design is based on a native animal of South America, the armadillo, a placental mammal with a leathery armor shell.
The research team imitated the animal"s distinctive protection characteristic of rolling up into a ball when facing with threat from predators. Just as armadillos hide themselves inside the shell, Armadillo-T tucks its rear body away, shrinking its original size of 2.8 meters (110 inches) down to almost half, 1.65 meters (65 inches), when folding.
Armadillo-T is a four-wheel-drive, all-electric car with two seats and four in-wheel motors. Since the motors are installed inside the wheels, and the 13.6 kWh capacity of lithium-ion battery pack is housed on the front side, the battery and motors do not have to change their positions when the car folds. This not only optimizes the energy efficiency but also provides stability and ample room to drivers and passengers.
Once folded, the small and light (weighs 450 kg) electric vehicle takes up only one-third of a 5-meter parking space, the standard parking size in Korea, allowing three of its kind to be parked. With a smartphone-interfaced remote control on the wheels, the vehicle can turn 360 degrees, enhancing drivers" convenience to park the car, even in an odd space in a parking lot, the corner of a building, for example.
Professor In-Soo Suh said, "I expect that people living in cities will eventually shift their preferences from bulky, petro-engine cars to smaller and lighter electric cars. Armadillo-T can be one of the alternatives city drivers can opt for. Particularly, this car is ideal for urban travels, including car-sharing and transit transfer, to offer major transportation links in a city. In addition to the urban application, local near-distance travels such as tourist zones or large buildings can be another example of application."
The concept car has loads of smart features on board, too: the cameras installed inside the car eliminate the need for side mirrors and increase the driver"s ability to see the car"s right and left side, thereby reducing blind spots. With a smartphone, the driver can control Armadillo-T and enable remote folding control. The car has a maximum speed of 60 km/h, and with a ten-minute fast charge, it can run up to 100 km.
Professor Suh explained that the concept of Armadillo-T was originally initiated in 2011 as he focused his research interest on the sub-A segment of personal mobility vehicles (PMVs), which are smaller and lighter than the current compact cars, as a new personalized transport mode.
"In coming years, we will see more mega-size cities established and face more serious environmental problems. Throughout the world, the aging population is rapidly growing as well. To cope with climate, energy, and limited petroleum resources, we really need to think outside the box, once again, to find more convenient and eco-friendly transportation, just as the Ford Model T did in the early 1920s. A further level of R&D, technical standards, and regulatory reviews are required to have these types of micro vehicles or PMVs on the market through test-bed evaluations, but we believe that Armadillo-T is an icon toward the future transport system with technology innovation."
The research project has been supported by the Korean government, the Ministry of Land, Infrastructure and Transport and the Korea Agency for Infrastructure Technology Advancement, since December 2012.Youtube Link: http://www.youtube.com/watch?v=8DoZH7Y-sR0
2013.08.21 View 13971 -
Board Chairman Chung Makes First Visit to Building Named After Him
Moon-Soul Chung, chairman of the KAIST board of trustees, visited the building built with his donation on Monday (Oct. 19) for the first time since he made the deed of gift eight years ago, university authorities said on Monday (Oct. 19).
In 2000, Chung, founder and former CEO of Mirae Corp, manufacturer of semiconductor testing equipment, announced retirement and handed over the presidency of his company to one of his managing directors. One year later in 2001, he donated 30 billion won, then equivalent to $30 million, to KAIST. It was by then the largest amount given by a single donor.
The major part of his donation went to constructing a building for the newly-established Department of Bio and Brain Engineering, and it was named after him. However, Chung did not attend the ground-breaking and dedication ceremonies, saying that he would not enter the building until KAIST achieved a breakthrough technology which can inject a hope to Koreans.
On his first visit to the building, he was briefed on the major research outcomes of the department over the past seven years, which were highlighted by the recent invention of an apparatus for measuring perfusion rate of legs. A KAIST team headed by Prof. Chul-Hee Choi invented a light leakage prevention unit including a light emitting device for radiating light having a certain wavelength onto a living body injected with Indocyanine Green (ICG).
According to Prof. Choi, the invention relates to an apparatus for measuring the perfusion rate of legs. The invention also includes a light leakage prevention housing formed to prevent transmission of external light.
Chung expressing satisfaction with the achievements and encouraged professors, researchers and students working at the Moon-Soul Chung Building.
2009.10.20 View 12865