NT
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Chair Professor Jo-Won Lee Named Sixth President of National Nano Fab Center
< President Jo-Won Lee >
Chair professor Jo-Won Lee from Hanyang University was appointed as the sixth president of the National Nano Fab Center (NNFC). President Lee will serve his term for three years from September 16.
The NNFC is an affiliated institution of KAIST, established in 2002 to foster qualified manpower in the field of nanotechnology (NT) in Korea. The NNFC features cutting-edge NT-related research equipment and fabrication services, and provides students and researchers quality education and training. The NNFC seeks to become a world-leading institute by performing extensive business operations including the commercialization of NT research results and conducting various multidisciplinary projects.
President Lee received his BS degree from Hanyang University and his MS and PhD degrees in metals science from the Pennsylvania State University. He taught nano-conversion science at his alma mater, Hanyang University, while serving as the director of the National Program for Tera-level Nanodevices. President Lee also guided the governmental planning committee for the 10-year Korea Nanotechnology Initiative as secretary general.
President Lee said, “The NNFC has been striving to develop Korea as the world’s strongest nation in nanotechnology thus far. All of the members of the NNFC will continue giving our best effort for the improvement of our nation’s nanotechnology.”
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2019.09.17 View 3961 -
Two More Cross-generation Collaborative Labs Open
< President Sung-Chul Shin (sixth from the left) and Professor Sun Chang Kim (seventh from the left) at the signboard ceremony of KAIST BioDesigneering Laboratory >
KAIST opened two more cross-generation collaborative labs last month. KAIST BioDesigneering Laboratory headed by Professor Sun Chang Kim from the Department of Biological Sciences and Nanophotonics Laboratory led by Professor Yong-Hee Lee from the Department of Physics have been selected to receive 500 million KRW funding for five years.
A four-member selection committee including the former President of ETH Zürich Professor Emeritus Ralph Eichler and Professor Kwang-Soo Kim of Harvard Medical School conducted a three-month review and evaluation for this selection to be made. With these two new labs onboard, a total of six cross-generation collaborative labs will be operated on campus.
The operation of cross-generation collaborative labs has been in trial since March last year, as one of the KAIST’s Vision 2031 research innovation initiatives. This novel approach is to pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires, so that the spectrum of knowledge and research competitiveness can be extended to future generations. The selected labs will be funded for five years, and the funding will be extended if necessary. KAIST will continue to select new labs every year.
One of this year’s selectees Professor Sun Chang Kim will be teamed up with Professor Byung-Kwan Cho from the same department and Professor Jung Kyoon Choi from the Department of Bio and Brain Engineering to collaborate in the fields of synthetic biology, systems biology, and genetic engineering. This group mainly aims at designing and synthesizing optimal genomes that can efficiently manufacture protein drug and biomedical active materials. They will also strive to secure large amounts of high-functioning natural active substances, new adhesive antibacterial peptides, and eco-friendly ecological restoration materials. It is expected that collaboration between these three multigenerational professors will help innovate their bio-convergence technology and further strengthen their international competitiveness in the global bio-market.
Another world-renowned scholar Professor Yong-Hee Lee of photonic crystal laser study will be joined by Professor Minkyo Seo from the same department and Professor Hansuek Lee from the Graduate School of Nanoscience and Technology. They will explore the extreme limits of light-material interaction based on optical micro/nano resonators, with the goal of developing future nonlinear optoelectronic and quantum optical devices. The knowledge and technology newly gained from the research are expected to provide an important platform for a diverse range of fields from quantum communications to biophysics.
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2019.09.06 View 10457 -
Algorithm Identifies Optimal Pairs for Composing Metal-Organic Frameworks
The integration of metal-organic frameworks (MOFs) and other metal nanoparticles has increasingly led to the creation of new multifunctional materials. Many researchers have integrated MOFs with other classes of materials to produce new structures with synergetic properties.
Despite there being over 70,000 collections of synthesized MOFs that can be used as building blocks, the precise nature of the interaction and the bonding at the interface between the two materials still remains unknown. The question is how to sort out the right matching pairs out of 70,000 MOFs.
An algorithmic study published in Nature Communications by a KAIST research team presents a clue for finding the perfect pairs. The team, led by Professor Ji-Han Kim from the Department of Chemical and Biomolecular Engineering, developed a joint computational and experimental approach to rationally design MOF@MOFs, a composite of MOFs where an MOF is grown on a different MOF.
Professor Kim’s team, in collaboration with UNIST, noted that the metal node of one MOF can coordinately bond with the linker of a different MOF and the precisely matched interface configurations at atomic and molecular levels can enhance the likelihood of synthesizing MOF@MOFs.
They screened thousands of MOFs and identified optimal MOF pairs that can seamlessly connect to one another by taking advantage of the fact that the metal node of one MOF can form coordination bonds with the linkers of the second MOF. Six pairs predicted from the computational algorithm successfully grew into single crystals.
This computational workflow can readily extend into other classes of materials and can lead to the rapid exploration of the composite MOFs arena for accelerated materials development. Even more, the workflow can enhance the likelihood of synthesizing MOF@MOFs in the form of large single crystals, and thereby demonstrated the utility of rationally designing the MOF@MOFs.
This study is the first algorithm for predicting the synthesis of composite MOFs, to the best of their knowledge. Professor Kim said, “The number of predicted pairs can increase even more with the more general 2D lattice matching, and it is worth investigating in the future.”
This study was supported by Samsung Research Funding & Incubation Center of Samsung Electronics.
(Figure: An example of a rationally synthesized MOF@MOFs (cubic HKUST-1@MOF-5 ))
2019.08.30 View 16632 -
Researchers Describe a Mechanism Inducing Self-Killing of Cancer Cells
(Professor Kim (left) and lead author Lee)
Researchers have described a new mechanism which induces the self-killing of cancer cells by perturbing ion homeostasis. A research team from the Department of Biochemical Engineering has developed helical polypeptide potassium ionophores that lead to the onset of programmed cell death. The ionophores increase the active oxygen concentration to stress endoplasmic reticulum to the point of cellular death.
The electrochemical gradient between extracellular and intracellular conditions plays an important role in cell growth and metabolism. When a cell’s ion homeostasis is disturbed, critical functions accelerating the activation of apoptosis are inhibited in the cell.
Although ionophores have been intensively used as an ion homeostasis disturber, the mechanisms of cell death have been unclear and the bio-applicability has been limited. In the study featured at Advanced Science, the team presented an alpha helical peptide-based anticancer agent that is capable of transporting potassium ions with water solubility. The cationic, hydrophilic, and potassium ionic groups were combined at the end of the peptide side chain to provide both ion transport and hydrophilic properties.
These peptide-based ionophores reduce the intracellular potassium concentration and at the same time increase the intracellular calcium concentration. Increased intracellular calcium concentrations produce intracellular reactive oxygen species, causing endoplasmic reticulum stress, and ultimately leading to apoptosis.
Anticancer effects were evaluated using tumor-bearing mice to confirm the therapeutic effect, even in animal models. It was found that tumor growth was strongly inhibited by endoplasmic stress-mediated apoptosis.
Lead author Dr. Dae-Yong Lee said, “A peptide-based ionophore is more effective than conventional chemotherapeutic agents because it induces apoptosis via elevated reactive oxygen species levels. Professor Yeu-Chun Kim said he expects this new mechanism to be widely used as a new chemotherapeutic strategy. This research was funded by the National Research Foundation.
2019.08.28 View 20177 -
Distinguished Professor Sukbok Chang Donates His Prize Money
The honoree of the 2019 Korea Best Scientist and Technologist Award, Distinguished Professor Sukbok Chang donated his prize money of one hundred million KRW to the Chemistry Department Scholarship Fund and the Lyu Keun-Chul Sports Complex Management Fund during a donation ceremony last week.
Professor Chang won the award last month in recognition of his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. Professor Chang, a world renowned chemist, has been recognized for his highly selective catalytic systems, allowing the controlled defunctionalization of bio-derived platform substrates under mild conditions and opening a new avenue for the utilization of biomass-derived platform chemicals.
“All my achievements are the results of my students’ hard work and dedication. I feel very fortunate to have such talented team members. I want to express my sincere gratitude for such a great research environment that we have worked together in so far,” said Professor Chang at the ceremony.
KAIST President Sung-Chul Shin said, “Not only will Professor Chang’s donation make a significant contribution to the Department of Chemistry, but also to the improvement of the Lyu Keun-Chul Sports Complex’s management, which directly links to the health and welfare of the KAIST community.”
Professor Chang currently holds the position of distinguished professor at KAIST and director of the Center for Catalytic Hydrocarbon Functionalizations in the Institute for Basic Science (IBS). He previously received the Kyung-Ahm Academic Award in 2013 and the Korea Toray Science Award in 2018. All these prize money also went to the school.
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2019.08.26 View 8241 -
Professor Sang Gyu Kim Receives Yeochon Award for Ecology
Professor Sang-Gyu Kim from the Department of Biological Sciences was selected as the winner of the 12th Yeochon Award for Ecology presented by the Yeochon Association for Ecological Research.
The award was conferred on August 13 in Jeju at the annual conference co-hosted by the Ecological Society of Korea and the Yeochon Association for Ecological Research. Professor Kim received 10 million KRW in prize money.
Professor Kim was recognized for his achievements and contributions in studying herbivorous insects ‘rice weevils’ and their host plant ‘wild tobacco’, especially for having explored the known facts in traditional ecology at the molecular level. His findings are presented in his paper titled ‘Trichobaris weevils distinguish amongst toxic host plants by sensing volatiles that do not affect larval performance’ published in Molecular Ecology in July 2016.
Furthermore, Professor Kim’s research team is continuing their work to identify the ecological functions of plant metabolites as well as interactions between flowers and insect vectors at the molecular level. In doing so, the team edits genes in various plant species using the latest gene editing technology.
The Yeochon Award for Ecology was first established in 2005 with funds donated by a senior ecologist, the late Honorary Professor Joon-Ho Kim of Seoul National University. The award is named after the professor’s pen name “Yeochon” and is intended to encourage promising next-generation ecologists to produce outstanding research achievements in the field of basic ecology.
Professor Kim said, “I will take this award as encouragement to continue taking challenging risks to observe ecological phenomenon from a new perspective. I will continue my research with my students with joy and enthusiasm.”
2019.08.14 View 6746 -
Manipulating Brain Cells by Smartphone
Researchers have developed a soft neural implant that can be wirelessly controlled using a smartphone. It is the first wireless neural device capable of indefinitely delivering multiple drugs and multiple colour lights, which neuroscientists believe can speed up efforts to uncover brain diseases such as Parkinson’s, Alzheimer’s, addiction, depression, and pain.
A team under Professor Jae-Woong Jeong from the School of Electrical Engineering at KAIST and his collaborators have invented a device that can control neural circuits using a tiny brain implant controlled by a smartphone. The device, using Lego-like replaceable drug cartridges and powerful, low-energy Bluetooth, can target specific neurons of interest using drugs and light for prolonged periods. This study was published in Nature Biomedical Engineering.
“This novel device is the fruit of advanced electronics design and powerful micro and nanoscale engineering,” explained Professor Jeong. “We are interested in further developing this technology to make a brain implant for clinical applications.”
This technology significantly overshadows the conventional methods used by neuroscientists, which usually involve rigid metal tubes and optical fibers to deliver drugs and light. Apart from limiting the subject’s movement due to bulky equipment, their relatively rigid structure causes lesions in soft brain tissue over time, therefore making them not suitable for long-term implantation. Although some efforts have been made to partly mitigate adverse tissue response by incorporating soft probes and wireless platforms, the previous solutions were limited by their inability to deliver drugs for long periods of time as well as their bulky and complex control setups.
To achieve chronic wireless drug delivery, scientists had to solve the critical challenge of the exhaustion and evaporation of drugs. To combat this, the researchers invented a neural device with a replaceable drug cartridge, which could allow neuroscientists to study the same brain circuits for several months without worrying about running out of drugs.
These ‘plug-n-play’ drug cartridges were assembled into a brain implant for mice with a soft and ultrathin probe (with the thickness of a human hair), which consisted of microfluidic channels and tiny LEDs (smaller than a grain of salt), for unlimited drug doses and light delivery.
Controlled with an elegant and simple user interface on a smartphone, neuroscientists can easily trigger any specific combination or precise sequencing of light and drug delivery in any implanted target animal without the need to be physically inside the laboratory. Using these wireless neural devices, researchers can also easily setup fully automated animal studies where the behaviour of one animal could affect other animals by triggering light and/or drug delivery.
“The wireless neural device enables chronic chemical and optical neuromodulation that has never been achieved before,” said lead author Raza Qazi, a researcher with KAIST and the University of Colorado Boulder.
This work was supported by grants from the National Research Foundation of Korea, US National Institute of Health, National Institute on Drug Abuse, and Mallinckrodt Professorship.
(A neural implant with replaceable drug cartridges and Bluetooth low-energy can target specific neurons .)
(Micro LED controlling using smartphone application)
2019.08.07 View 32294 -
Chem-E-Car Team to Vie for World Title
Team KAItalyst, composed of KAIST undergraduate students, celebrated victory in the regional qualifying rounds of the 2019 International Chem-E-Car Competition held at KAIST’s Main Campus in Daejeon on July 20. The high finish in the national rankings qualified the team for a trip to the world finals to be held in Orlando, Florida, USA, in November.
The Chem-E-Car Competition involves designing and building a shoebox-sized model car that is powered and controlled by chemical reactions. University students from all over the world have been actively participating in this competition since the competition was introduced by the American Institute of Chemical Engineers (AIChE) in 1999.
KAIST first entered the competition in 2014, won the world finals in 2016, and then received the Most Consistent Award in 2017 and 2018. In recognition of KAIST’s consistently outstanding performance in the competition, AIChE asked KAIST to host this year’s regional competition for the first time in Korea.
Although a number of Korean university student teams have shown great interest in participating in this regional competition, most were not able to successfully implement their technology, and only two teams each from KAIST and Seoul National University (SNU) joined the competition.
Each team collaborated to fabricate a chemically powered model car that could carry a payload, and travel any distance between 15 and 30 meters. The weight of the payload and the travelling distance were randomly set an hour before the competition started, to require the participating teams adapt and perform calculations in a short period of time. The goal was to stop travelling exactly at the randomly chosen distance. The car closest to the finish line at the end of the race earned the highest amount of points. Precise control over chemical reactions was key to landing directly on the mark.
Team KAItalyst, consisting of six KAIST undergraduate students majoring in chemical and biomolecular engineering and mechanical engineering, beat their SNU rivals by stopping their car 1.5 meters closer to the goal at the end of the 22.5 meter-long race. Team KAItalyst loaded vanadium redox flow batteries onto their car to stabilize its output, and further increased the accuracy and velocity of chemical reactions through iodine clock reactions. 200 USD was awarded to Team KAItalyst, and 100 USD in prize money went to the SNU team.
KAItalyst team leader Jee-Hyun Hong said, “This was the first time for us to develop and drive our own chemically-powered model car, and we learned a lot from the challenges we faced,” Hong continued, “We will step up our efforts to perform better in the upcoming international competition.” The world finals will be held during the AIChE Fall Meeting in Orlando, Florida in November. Students from over 50 universities worldwide including the Georgia Institute of Technology and Carnegie Mellon University will compete against each other. The first, second, and third prizes at the finals will be 2,000, 1,000, and 500 USD respectively.
Professor Dong-Yeun Koh of the KAIST Chemical and Biomolecular Engineering Department who advised Team KAItalyst remarked, “I hope this year’s regional competition that KAIST held for the first time as a Korean university will be a possible starting point for more Korean universities to participate and compete in the future.”
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2019.08.05 View 6580 -
Synthesizing Single-Crystalline Hexagonal Graphene Quantum Dots
(Figure: Uniformly ordered single-crystalline graphene quantum dots of various sizes synthesized through solution chemistry.)
A KAIST team has designed a novel strategy for synthesizing single-crystalline graphene quantum dots, which emit stable blue light. The research team confirmed that a display made of their synthesized graphene quantum dots successfully emitted blue light with stable electric pressure, reportedly resolving the long-standing challenges of blue light emission in manufactured displays. The study, led by Professor O Ok Park in the Department of Chemical and Biological Engineering, was featured online in Nano Letters on July 5.
Graphene has gained increased attention as a next-generation material for its heat and electrical conductivity as well as its transparency. However, single and multi-layered graphene have characteristics of a conductor so that it is difficult to apply into semiconductor. Only when downsized to the nanoscale, semiconductor’s distinct feature of bandgap will be exhibited to emit the light in the graphene. This illuminating featuring of dot is referred to as a graphene quantum dot.
Conventionally, single-crystalline graphene has been fabricated by chemical vapor deposition (CVD) on copper or nickel thin films, or by peeling graphite physically and chemically. However, graphene made via chemical vapor deposition is mainly used for large-surface transparent electrodes. Meanwhile, graphene made by chemical and physical peeling carries uneven size defects.
The research team explained that their graphene quantum dots exhibited a very stable single-phase reaction when they mixed amine and acetic acid with an aqueous solution of glucose. Then, they synthesized single-crystalline graphene quantum dots from the self-assembly of the reaction intermediate. In the course of fabrication, the team developed a new separation method at a low-temperature precipitation, which led to successfully creating a homogeneous nucleation of graphene quantum dots via a single-phase reaction.
Professor Park and his colleagues have developed solution phase synthesis technology that allows for the creation of the desired crystal size for single nanocrystals down to 100 nano meters. It is reportedly the first synthesis of the homogeneous nucleation of graphene through a single-phase reaction.
Professor Park said, "This solution method will significantly contribute to the grafting of graphene in various fields. The application of this new graphene will expand the scope of its applications such as for flexible displays and varistors.”
This research was a joint project with a team from Korea University under Professor Sang Hyuk Im from the Department of Chemical and Biological Engineering, and was supported by the National Research Foundation of Korea, the Nano-Material Technology Development Program from the Electronics and Telecommunications Research Institute (ETRI), KAIST EEWS, and the BK21+ project from the Korean government.
2019.08.02 View 33295 -
KAIST-Google Partnership for AI Education and Research
Google has agreed to support KAIST students and professors in the fields of AI research and education. President Sung-Chul Shin and Google Korea Country Director John Lee signed the collaboration agreement during a ceremony on July 19 at KAIST.
Under the agreement, Google will fund the Google AI-Focused Research Awards Program, the PhD Fellowship Program, and Student Travel Grants for KAIST. In addition, Google will continue to provide more academic and career building opportunities for students, including Google internship programs.
KAIST and Google has been collaborating for years. Professor Steven Whang at the School of Electrical Engineering and Professor Sung Ju Hwang at the School of Computing won the AI-Focused Award in 2018 and conduct their researches on "Improving Generalization and Reliability of Any Deep Neural Networks" and "Automatic and Acitionable Model Analysis for TFX," respectively. Outstanding PhD students have been recognized through the PhD Fellowship Program. However, this new collaboration agreement will focus on research, academic development, and technological innovation in AI.
Google plans to support research in the fields of deep learning, cloud machine learning, and voice technologies. Google will fund the development of two educational programs based on Google open source technology each year for two years that will be used in the new AI Graduate School opening for the fall semester.
John Lee of Google Korea said, “This partnership lays a solid foundation for deeper collaboration.” President Shin added, “This partnership will not only advance Korea’s global competitiveness in AI-powered industries but also contribute to the global community by nurturing talents in this most extensive discipline.”
2019.07.22 View 8352 -
Flexible User Interface Distribution for Ubiquitous Multi-Device Interaction
< Research Group of Professor Insik Shin (center) >
KAIST researchers have developed mobile software platform technology that allows a mobile application (app) to be executed simultaneously and more dynamically on multiple smart devices. Its high flexibility and broad applicability can help accelerate a shift from the current single-device paradigm to a multiple one, which enables users to utilize mobile apps in ways previously unthinkable.
Recent trends in mobile and IoT technologies in this era of 5G high-speed wireless communication have been hallmarked by the emergence of new display hardware and smart devices such as dual screens, foldable screens, smart watches, smart TVs, and smart cars. However, the current mobile app ecosystem is still confined to the conventional single-device paradigm in which users can employ only one screen on one device at a time. Due to this limitation, the real potential of multi-device environments has not been fully explored.
A KAIST research team led by Professor Insik Shin from the School of Computing, in collaboration with Professor Steve Ko’s group from the State University of New York at Buffalo, has developed mobile software platform technology named FLUID that can flexibly distribute the user interfaces (UIs) of an app to a number of other devices in real time without needing any modifications. The proposed technology provides single-device virtualization, and ensures that the interactions between the distributed UI elements across multiple devices remain intact.
This flexible multimodal interaction can be realized in diverse ubiquitous user experiences (UX), such as using live video steaming and chatting apps including YouTube, LiveMe, and AfreecaTV. FLUID can ensure that the video is not obscured by the chat window by distributing and displaying them separately on different devices respectively, which lets users enjoy the chat function while watching the video at the same time.
In addition, the UI for the destination input on a navigation app can be migrated into the passenger’s device with the help of FLUID, so that the destination can be easily and safely entered by the passenger while the driver is at the wheel.
FLUID can also support 5G multi-view apps – the latest service that allows sports or games to be viewed from various angles on a single device. With FLUID, the user can watch the event simultaneously from different viewpoints on multiple devices without switching between viewpoints on a single screen.
PhD candidate Sangeun Oh, who is the first author, and his team implemented the prototype of FLUID on the leading open-source mobile operating system, Android, and confirmed that it can successfully deliver the new UX to 20 existing legacy apps.
“This new technology can be applied to next-generation products from South Korean companies such as LG’s dual screen phone and Samsung’s foldable phone and is expected to embolden their competitiveness by giving them a head-start in the global market.” said Professor Shin.
This study will be presented at the 25th Annual International Conference on Mobile Computing and Networking (ACM MobiCom 2019) October 21 through 25 in Los Cabos, Mexico. The research was supported by the National Science Foundation (NSF) (CNS-1350883 (CAREER) and CNS-1618531).
Figure 1. Live video streaming and chatting app scenario
Figure 2. Navigation app scenario
Figure 3. 5G multi-view app scenario
Publication: Sangeun Oh, Ahyeon Kim, Sunjae Lee, Kilho Lee, Dae R. Jeong, Steven Y. Ko, and Insik Shin. 2019. FLUID: Flexible User Interface Distribution for Ubiquitous Multi-device Interaction. To be published in Proceedings of the 25th Annual International Conference on Mobile Computing and Networking (ACM MobiCom 2019). ACM, New York, NY, USA. Article Number and DOI Name TBD.
Video Material:
https://youtu.be/lGO4GwH4enA
Profile: Prof. Insik Shin, MS, PhD
ishin@kaist.ac.kr
https://cps.kaist.ac.kr/~ishin
Professor
Cyber-Physical Systems (CPS) Lab
School of Computing
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Sangeun Oh, PhD Candidate
ohsang1213@kaist.ac.kr
https://cps.kaist.ac.kr/
PhD Candidate
Cyber-Physical Systems (CPS) Lab
School of Computing
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Prof. Steve Ko, PhD
stevko@buffalo.edu
https://nsr.cse.buffalo.edu/?page_id=272
Associate Professor
Networked Systems Research Group
Department of Computer Science and Engineering
State University of New York at Buffalo
http://www.buffalo.edu/ Buffalo 14260, USA
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2019.07.20 View 39662 -
Mathematical Modeling Makes a Breakthrough for a New CRSD Medication
PhD Candidate Dae Wook Kim (Left) and Professor Jae Kyoung Kim (Right)
- Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy -
Mathematicians’ new modeling has identified major sources of interspecies and inter-individual variations in the clinical efficacy of a clock-modulating drug: photosensitivity and PER2 level. This enabled precision medicine for circadian disruption.
A KAIST mathematics research team led by Professor Jae Kyoung Kim, in collaboration with Pfizer, applied a combination of mathematical modeling and simulation tools for circadian rhythms sleep disorders (CRSDs) to analyze the animal data generated by Pfizer. This study was reported in Molecular Systems Biology as the cover article on July 8.
Pharmaceutical companies have conducted extensive studies on animals to determine the candidacy of this new medication. However, the results of animal testing do not always translate to the same effects in human trials. Furthermore, even between humans, efficacy differs across individuals depending on an individual’s genetic and environmental factors, which require different treatment strategies.
To overcome these obstacles, KAIST mathematicians and their collaborators developed adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions.
A circadian rhythm is a 24-hour cycle in the physiological processes of living creatures, including humans. A biological clock in the hypothalamic suprachiasmatic nucleus in the human brain sets the time for various human behaviors such as sleep.
A disruption of the endogenous timekeeping system caused by changes in one’s life pattern leads to advanced or delayed sleep-wake cycle phase and a desynchronization between sleep-wake rhythms, resulting in CRSDs. To restore the normal timing of sleep, timing of the circadian clock could be adjusted pharmacologically.
Pfizer identified PF-670462, which can adjust the timing of circadian clock by inhibiting the core clock kinase of the circadian clock (CK1d/e). However, the efficacy of PF-670462 significantly differs between nocturnal mice and diurnal monkeys, whose sleeping times are opposite.
The research team discovered the source of such interspecies variations in drug response by performing thousands of virtual experiments using a mathematical model, which describes biochemical interactions among clock molecules and PF-670462. The result suggests that the effect of PF-670462 is reduced by light exposure in diurnal primates more than in nocturnal mice. This indicates that the strong counteracting effect of light must be considered in order to effectively regulate the circadian clock of diurnal humans using PF-670462.
Furthermore, the team also found the source of inter-patients variations in drug efficacy using virtual patients whose circadian clocks were disrupted due to various mutations. The degree of perturbation in the endogenous level of the core clock molecule PER2 affects the efficacy.
This explains why the clinical outcomes of clock-modulating drugs are highly variable and certain subtypes are unresponsive to treatment. Furthermore, this points out the limitations of current treatment strategies tailored to only the patient’s sleep and wake time but not to the molecular cause of sleep disorders.
PhD candidate Dae Wook Kim, who is the first author, said that this motivates the team to develop an adaptive chronotherapy, which identifies a personalized optimal dosing time of day by tracking the sleep-wake up time of patients via a wearable device and allows for a precision medicine approach for CRSDs.
Professor Jae Kyoung Kim said, "As a mathematician, I am excited to help enable the advancement of a new drug candidate, which can improve the lives of so many patients. I hope this result promotes more collaborations in this translational research.”
This research was supported by a Pfizer grant to KAIST (G01160179), the Human Frontiers Science Program Organization (RGY0063/2017), and a National Research Foundation (NRF) of Korea Grant (NRF-2016 RICIB 3008468 and NRF-2017-Fostering Core Leaders of the Future Basic Science Program/ Global Ph.D. Fellowship Program).
Figure 1. Interspecies and Inter-patients Variations in PF-670462 Efficacy
Figure 2. Journal Cover Page
Publication:
Dae Wook Kim, Cheng Chang, Xian Chen, Angela C Doran, Francois Gaudreault, Travis Wager, George J DeMarco, and Jae Kyoung Kim. 2019. Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy. Molecular Systems Biology. EMBO Press, Heidelberg, Germany, Vol. 15, Issue No. 7, Article, 16 pages. https://doi.org/10.15252/msb.20198838
Profile: Prof. Jae Kyoung Kim, PhD
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
Associate Professor
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dae Wook Kim, PhD Candidate
0308kdo@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
PhD Candidate
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dr. Cheng Chang, PhD
cheng.chang@pfizer.com
Associate Director of Clinical Pharmacology
Clinical Pharmacology, Global Product Development
Pfizer
https://www.pfizer.com/ Groton 06340, USA
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2019.07.09 View 35429