SCIE
-
A Mathematical Model Reveals Long-Distance Cell Communication Mechanism
How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping?
A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Krešimir Josić at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology.
Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities.
The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator.
Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, “That’s why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules.” Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells.
The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. “It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That’s why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time,” said Professor Kim.
Professor Kim added, “Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics."
The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research.
(Figure: Complex molecular interactions among microbial consortia is simplified as interactions among points on a limit cycle (right).)
2019.10.15 View 24066 -
Two Professors Recognized for the National R&D Excellence 100
< Professor Haeng-Ki Lee (left) and Professor Jeong-Ho Lee (right) >
Two KAIST professors were listed among the 2019 National R&D Excellence 100 announced by the Ministry of Science and ICT and the Korea Institute of S&T Evaluation and Planning.
Professor Haeng-Ki Lee from the Department of Civil and Environmental Engineering was recognized in the field of mechanics and materials for his research on developing new construction materials through the convergence of nano- and biotechnologies.
In the field of life and marine science, Professor Jeong-Ho Lee from the Graduate School of Medical Science and Engineering was lauded for his research of diagnostic tools and therapies for glioblastoma and pediatric brain tumors.
A certificate from the Minister of Ministry of Science and ICT will be conferred to these two professors, and their names will be inscribed on a special 2019 National R&D Excellence 100 plaque to celebrate their achievements. The professors will also be given privileges during the process of new R&D project selection.
(END)
2019.10.15 View 9376 -
Professor Byong-Guk Park Named Scientist of October
< Professor Byong-Guk Park >
Professor Byong-Guk Park from the Department of Materials Science and Engineering was selected as the ‘Scientist of the Month’ for October 2019 by the Ministry of Science and ICT and the National Research Foundation of Korea. Professor Park was recognized for his contributions to the advancement of spin-orbit torque (SOT)-based magnetic random access memory (MRAM) technology. He received 10 million KRW in prize money.
A next-generation, non-volatile memory device MRAM consists of thin magnetic films. It can be applied in “logic-in-memory” devices, in which logic and memory functionalities coexist, thus drastically improving the performance of complementary metal-oxide semiconductor (CMOS) processors. Conventional MRAM technology is limited in its ability to increase the operation speed of a memory device while maintaining a high density.
Professor Park tackled this challenge by introducing a new material, antiferromagnet (IrMn), that generates a sizable amount of SOT as well as an exchange-bias field, which makes successful data writing possible without an external magnetic field. This research outcome paved the way for the development of MRAM, which has a simple device structure but features high speeds and density.
Professor Park said, “I feel rewarded to have forwarded the feasibility and applicability of MRAM. I will continue devoting myself to studying further on the development of new materials that can help enhance the performance of memory devices."
(END)
2019.10.10 View 8131 -
Object Identification and Interaction with a Smartphone Knock
(Professor Lee (far right) demonstrate 'Knocker' with his students.)
A KAIST team has featured a new technology, “Knocker”, which identifies objects and executes actions just by knocking on it with the smartphone. Software powered by machine learning of sounds, vibrations, and other reactions will perform the users’ directions.
What separates Knocker from existing technology is the sensor fusion of sound and motion. Previously, object identification used either computer vision technology with cameras or hardware such as RFID (Radio Frequency Identification) tags. These solutions all have their limitations. For computer vision technology, users need to take pictures of every item. Even worse, the technology will not work well in poor lighting situations. Using hardware leads to additional costs and labor burdens.
Knocker, on the other hand, can identify objects even in dark environments only with a smartphone, without requiring any specialized hardware or using a camera. Knocker utilizes the smartphone’s built-in sensors such as a microphone, an accelerometer, and a gyroscope to capture a unique set of responses generated when a smartphone is knocked against an object. Machine learning is used to analyze these responses and classify and identify objects.
The research team under Professor Sung-Ju Lee from the School of Computing confirmed the applicability of Knocker technology using 23 everyday objects such as books, laptop computers, water bottles, and bicycles. In noisy environments such as a busy café or on the side of a road, it achieved 83% identification accuracy. In a quiet indoor environment, the accuracy rose to 98%.
The team believes Knocker will open a new paradigm of object interaction. For instance, by knocking on an empty water bottle, a smartphone can automatically order new water bottles from a merchant app. When integrated with IoT devices, knocking on a bed’s headboard before going to sleep could turn off the lights and set an alarm. The team suggested and implemented 15 application cases in the paper, presented during the 2019 ACM International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2019) held in London last month.
Professor Sung-Ju Lee said, “This new technology does not require any specialized sensor or hardware. It simply uses the built-in sensors on smartphones and takes advantage of the power of machine learning. It’s a software solution that everyday smartphone users could immediately benefit from.” He continued, “This technology enables users to conveniently interact with their favorite objects.”
The research was supported in part by the Next-Generation Information Computing Development Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT and an Institute for Information & Communications Technology Promotion (IITP) grant funded by the Ministry of Science and ICT.
Figure: An example knock on a bottle. Knocker identifies the object by analyzing a unique set of responses from the knock, and automatically launches a proper application or service.
2019.10.02 View 25280 -
Professor Ki-Jun Yoon selected as the 2019 SUHF Young Investigator
< Professor Ki-Jun Yoon >
Professor Ki-Jun Yoon from the Department of Biological Sciences was named one of four recipients of the 2019 Suh Kyung-Bae Science Foundation (SUHF) Young Investigator Awards.
The SUHF is a non-profit organization established in 2016 and funded by a personal donation of 300 billion KRW in shares from Chairman and CEO Kyung-Bae Suh of the Amorepacific Group. The primary purpose of the foundation is to serve as a platform to nurture and provide comprehensive long-term support for creative and passionate young Korean scientists committed to pursuing research in the field of life sciences. The SUHF selects three to five scientists through an open recruiting process every year, and grants each scientist a maximum of 2.5 billion KRW over a period of up to five years.
Since January this year, the foundation received 83 research proposals from scientists across the nation, especially from those who had less than five years of experience as professors, and selected the four recipients, including Professor Yoon.
Professor Yoon was recognized for his contributions to the advancement of research on how post-transcriptional mechanisms may modulate stem cell properties. His research project involves deciphering the molecular mechanisms controlling RNA metabolism in neural stem cells during normal development, and how alterations in RNA regulatory programs lead to human brain disorders.
< (From left) Professor Joo-Hong Park, Professor Yuree Lee, Chairman and CEO Kyung-Bae Suh, Professor Eunjung Lee, Professor Ki-Jun Yoon, ⓒ Amorepacific Group >
The other awards were given to Professor Joo-Hong Park and Professor Yuree Lee of Seoul National University, and Professor Eunjung Lee of Boston Children's Hospital and Harvard Medical School.
The awards ceremony was held on September 18 at the Amorepacific Headquarters in Seoul.
With these four new awardees, a total of 14 scientists have been named as SUHF Young Investigators to date.
(END)
2019.09.23 View 7543 -
Sungjoon Park Named Google PhD Fellow
PhD candidate Sungjoon Park from the School of Computing was named a 2019 Google PhD Fellow in the field of natural language processing. The Google PhD fellowship program has recognized and supported outstanding graduate students in computer science and related fields since 2009. Park is one of three Korean students chosen as the recipients of Google Fellowships this year. A total of 54 students across the world in 12 fields were awarded this fellowship.
Park’s research on computational psychotherapy using natural language processing (NLP) powered by machine learning earned him this year’s fellowship. He presented of learning distributed representations in Korean and their interpretations during the 2017 Annual Conference of the Association for Computational Linguistics and the 2018 Conference on Empirical Methods in Natural Language Processing. He also applied machine learning-based natural language processing into computational psychotherapy so that a trained machine learning model could categorize client's verbal responses in a counseling dialogue. This was presented at the Annual Conference of the North American Chapter of the Association for Computational Linguistics.
More recently, he has been developing on neural response generation model and the prediction and extraction of complex emotion in text, and computational psychotherapy applications.
2019.09.17 View 6946 -
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 18078 -
Accurate Detection of Low-Level Somatic Mutation in Intractable Epilepsy
KAIST medical scientists have developed an advanced method for perfectly detecting low-level somatic mutation in patients with intractable epilepsy. Their study showed that deep sequencing replicates of major focal epilepsy genes accurately and efficiently identified low-level somatic mutations in intractable epilepsy.
According to the study, their diagnostic method could increase the accuracy up to 100%, unlike the conventional sequencing analysis, which stands at about 30% accuracy. This work was published in Acta Neuropathologica.
Epilepsy is a neurological disorder common in children. Approximately one third of child patients are diagnosed with intractable epilepsy despite adequate anti-epileptic medication treatment.
Somatic mutations in mTOR pathway genes, SLC35A2, and BRAF are the major genetic causes of intractable epilepsies. A clinical trial to target Focal Cortical Dysplasia type II (FCDII), the mTOR inhibitor is underway at Severance Hospital, their collaborator in Seoul, Korea. However, it is difficult to detect such somatic mutations causing intractable epilepsy because their mutational burden is less than 5%, which is similar to the level of sequencing artifacts. In the clinical field, this has remained a standing challenge for the genetic diagnosis of somatic mutations in intractable epilepsy.
Professor Jeong Ho Lee’s team at the Graduate School of Medical Science and Engineering analyzed paired brain and peripheral tissues from 232 intractable epilepsy patients with various brain pathologies at Severance Hospital using deep sequencing and extracted the major focal epilepsy genes.
They narrowed down target genes to eight major focal epilepsy genes, eliminating almost all of the false positive calls using deep targeted sequencing. As a result, the advanced method robustly increased the accuracy and enabled them to detect low-level somatic mutations in unmatched Formalin Fixed Paraffin Embedded (FFPE) brain samples, the most clinically relevant samples.
Professor Lee conducted this study in collaboration with Professor Dong Suk Kim and Hoon-Chul Kang at Severance Hospital of Yonsei University. He said, “This advanced method of genetic analysis will improve overall patient care by providing more comprehensive genetic counseling and informing decisions on alternative treatments.”
Professor Lee has investigated low-level somatic mutations arising in the brain for a decade. He is developing innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma at a tech-startup called SoVarGen. “All of the technologies we used during the research were transferred to the company. This research gave us very good momentum to reach the next phase of our startup,” he remarked.
The work was supported by grants from the Suh Kyungbae Foundation, a National Research Foundation of Korea grant funded by the Ministry of Science and ICT, the Korean Health Technology R&D Project from the Ministry of Health & Welfare, and the Netherlands Organization for Health Research and Development.
(Figure: Landscape of somatic and germline mutations identified in intractable epilepsy patients. a Signaling pathways for all of the mutated genes identified in this study. Bold: somatic mutation, Regular: germline mutation. b The distribution of variant allelic frequencies (VAFs) of identified somatic mutations. c The detecting rate and types of identified mutations according to histopathology. Yellow: somatic mutations, green: two-hit mutations, grey: germline mutations.)
2019.08.14 View 26936 -
Newly Identified Meningeal Lymphatic Vessels Answers the Key Questions on Brain Clearance
(Figure: Schematic images of location and features of meningeal lymphatic vessels and their changes associated with ageing.)
Just see what happens when your neighborhood’s waste disposal system is out of service. Not only do the piles of trash stink but they can indeed hinder the area’s normal functioning. That is also the case when the brain’s waste management is on the blink.
The buildup of toxic proteins in the brain causes a massive damage to the nerves, leading to cognitive dysfunction and increased probability of developing neurodegenerative disorders such as Alzheimer's disease. Though the brain drains its waste via the cerebrospinal fluid (CSF), little has been understood about an accurate route for the brain’s cleansing mechanism.
Medical scientists led by Professor Gou Young Koh at the Graduate School of Medical Science and Engineering have reported the basal side of the skull as the major route, so called “hotspot” for CSF drainage.
They found that basal meningeal lymphatic vessels (mLVs) function as the main plumbing pipes for CSF. They confirmed macromolecules in the CSF mainly runs through the basal mLVs. Notably, the team also revealed that the brain’s major drainage system, specifically basal mLVs are impaired with aging. Their findings have been reported in the journal Nature on July 24.
Throughout our body, excess fluids and waste products are removed from tissues via lymphatic vessels. It was only recently discovered that the brain also has a lymphatic drainage system. mLVs are supposed to carry waste from the brain tissue fluid and the CSF down the deep cervical lymph nodes for disposal. Still scientist are left with one perplexing question — where is the main exit for the CSF? Though mLVs in the upper part of the skull (dorsal meningeal lymphatic vessels) were reported as the brain’s clearance pathways in 2014, no substantial drainage mechanism was observed in that section.
“As a hidden exit for CSF, we looked into the mLVs trapped within complex structures at the base of the skull,” says Dr. Ji Hoon Ahn, the first author of this study. The researchers used several techniques to characterize the basal mLVs in detail. They used a genetically engineered lymphatic-reporter mouse model to visualize mLVs under a fluorescence microscope. By performing a careful examination of the mice skull, they found distinctive features of basal mLVs that make them suitable for CSF uptake and drainage. Just like typical functional lymphatic vessels, basal mLVs are found to have abundant lymphatic vessel branches with finger-like protrusions. Additionally, valves inside the basal mLVs allow the flow to go in one direction. In particular, they found that the basal mLVs are closely located to the CSF. Dr. Hyunsoo Cho, the first author of this study explains, “All up, it seemed a solid case that basal mLVs are the brain’s main clearance pathways.
The researchers verified such specialized morphologic characteristics of basal mLVs indeed facilitate the CSF uptake and drainage. Using CSF contrast-enhanced magnetic resonance imaging in a rat model, they found that CSF is drained preferentially through the basal mLVs. They also utilized a lymphatic-reporter mouse model and discovered that fluorescence-tagged tracer injected into the brain itself or the CSF is cleared mainly through the basal mLVs. Jun-Hee Kim, the first author of this study notes, “We literally saw that the brain clearance mechanism utilizing basal outflow route to exit the skull.
It has long been suggested that CSF turnover and drainage declines with ageing. However, alteration of mLVs associated with ageing is poorly understood. In this study, the researchers observed changes of mLVs in young (3-month-old) and aged (24~27-months-old) mice. They found that the structure of the basal mLVs and their lymphatic valves in aged mice become severely flawed, thus hampering CSF clearance. The corresponding author of this study, Dr. Koh says, “By characterizing the precise route for fluids leaving the brain, this study improves our understanding on how waste is cleared from the brain. Our findings also provide further insights into the role of impaired CSF clearance in the development of age-related neurodegenerative diseases.”
Many current therapies for Alzheimer’s disease target abnormally accumulated proteins, such as beta-amyloid. By mapping out a precise route for the brain’s waste clearance system, this study may be able to help find ways to improve the brain’s cleansing function. Such breakthrough might become quite a sensational strategy for eliminating the buildup of aging-related toxic proteins. “It definitely warrants more extensive investigation of mLVs in patients with age-related neurodegenerative disease such as Alzheimer’s disease prior to clinical investigation,” adds Professor Koh.
2019.07.25 View 31046 -
President Shin Shares Innovation Strategy at Moscow
President Sung-Chul Shin shared the recipe for success for rapid national development through university education during the Island 10-22 Conference held at the Skolov Institute of Science and Technology in Moscow on July 16.
President Shin stressed how urgent it is for higher education to rapidly embrace the new global economic environment brought about by the Fourth Industrial Revolution in his keynote address entitled ‘Roles and Responsibilities of Universities for Rapid National Development’.
The Island 10-22 Conference is a summit co-organized by the National University of Science and Technology MISIS and University of the National Technological Initiative 2035 and supported by the Ministry of Science and Higher Education of the Russian Federation. More than 30 world-renowned experts, presidents of leading technological universities including President Peretz Lavie from the Israel Institute of Technology Technion, President Scott Pulsipher from Western Governors University and specialists in big data participated in the conference as speakers and discussed a diverse spectrum of ideas for making innovations and digital transformations in universities. More than 1,600 participants joined the conference.
During his keynote speech, President Shin explained how Korea has achieved such rapid economic growth over the past half century. He cited the Korean government’s vision and innovation policies as factors leading to Korea’s phenomenal success. KAIST, one of the results of the Korean government’s innovation policy, led the nation to advanced technological breakthroughs in industries such as semiconductors. Such visionary policies and investments in science, technology, and education eventually made the Korea of today possible.
President Shin said that KAIST distinguished itself through its new vision of C3 that fosters intellectual creativity, caring for others, and a challenging mind . Under Vision 2031, a blueprint for becoming a leading global university, President Shin said the KAIST continues to strive for innovations in convergent education,research and entreprenurship.
2019.07.18 View 5303 -
High-Performance Sodium Ion Batteries Using Copper Sulfide
(Prof.Yuk and his two PhD candidates Parks)
Researchers presented a new strategy for extending sodium ion batteries’ cyclability using copper sulfide as the electrode material. This strategy has led to high-performance conversion reactions and is expected to advance the commercialization of sodium ion batteries as they emerge as an alternative to lithium ion batteries.
Professor Jong Min Yuk’s team confirmed the stable sodium storage mechanism using copper sulfide, a superior electrode material that is pulverization-tolerant and induces capacity recovery. Their findings suggest that when employing copper sulfide, sodium ion batteries will have a lifetime of more than five years with one charge per a day. Even better, copper sulfide, composed of abundant natural materials such as copper and sulfur, has better cost competitiveness than lithium ion batteries, which use lithium and cobalt.
Intercalation-type materials such as graphite, which serve as commercialized anode materials in lithium ion batteries, have not been viable for high-capacity sodium storage due to their insufficient interlayer spacing. Thus, conversion and alloying reactions type materials have been explored to meet higher capacity in the anode part. However, those materials generally bring up large volume expansions and abrupt crystallographic changes, which lead to severe capacity degradation.
The team confirmed that semi-coherent phase interfaces and grain boundaries in conversion reactions played key roles in enabling pulverization-tolerant conversion reactions and capacity recovery, respectively.
Most of conversion and alloying reactions type battery materials usually experience severe capacity degradations due to having completely different crystal structures and large volume expansion before and after the reactions. However, copper sulfides underwent a gradual crystallographic change to make the semi-coherent interfaces, which eventually prevented the pulverization of particles. Based on this unique mechanism, the team confirmed that copper sulfide exhibits a high capacity and high cycling stability regardless of its size and morphology.
Professor Yuk said, “Sodium ion batteries employing copper sulfide can advance sodium ion batteries, which could contribute to the development of low-cost energy storage systems and address the micro-dust issue”
This study was posted in Advanced Science on April 26 online and selected as the inside back cover for June issue.
(Figure: Schematic model demonstrating grain boundaries and phase interfaces formations.)
2019.07.15 View 26635 -
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
(END)
2019.07.09 View 33523