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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 35566 -
Two Alumni Win the Korea Best Scientist and Technologist Awards
Vice Chairman Ki-Nam Kim (Left) and Distinguished Professor Sukbok Chang (Right)
<ⓒ Photo by MSIT and KOFST>
Distinguished KAIST Professor Sukbok Chang from the Department of Chemistry and Vice Chairman Ki-Nam Kim of Samsung Electronics were selected as the winners of the “2019 Korea Best Scientist and Technologist Awards” by the Ministry of Science and ICT (MSIT) and the Korean Federation of Science and Technology Societies (KOFST). The awards, which were first handed out in 2003, are the highest honor bestowed to the two most outstanding scientists in Korea every year, and this year’s awardees are of greater significance as they are both KAIST alumni.
Professor Chang was recognized for his pioneering achievements and lifetime contributions to the development of carbon-hydrogen activation strategies, especially for carbon-carbon, carbon-nitrogen, and carbon-oxygen formations. His research group has also been actively involved in the development of 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. The results of his study have been introduced worldwide through many prestigious journals including Science, Nature Chemistry, and Nature Catalysis, making him one of the world's top 1% researchers by the number of references made to his papers by his peers over four consecutive years from 2015 to 2018.
Vice Chairman Kim, who received his M.E. degree from KAIST’s School of Electrical Engineering in 1983, has been credited with playing a leading role in the development of system semiconductors.
The awards were conferred on July 4 at the opening ceremony of the 2019 Korea Science and Technology Annual Meeting.
(END)
2019.07.09 View 12197 -
Deep Learning-Powered 'DeepEC' Helps Accurately Understand Enzyme Functions
(Figure: Overall scheme of DeepEC)
A deep learning-powered computational framework, ‘DeepEC,’ will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions.
A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner.
DeepEC takes a protein sequence as an input and accurately predicts EC numbers as an output. Enzymes are proteins that catalyze biochemical reactions and EC numbers consisting of four level numbers (i.e., a.b.c.d) indicate biochemical reactions. Thus, the identification of EC numbers is critical for accurately understanding enzyme functions and metabolism.
EC numbers are usually given to a protein sequence encoding an enzyme during a genome annotation procedure. Because of the importance of EC numbers, several EC number prediction tools have been developed, but they have room for further improvement with respect to computation time, precision, coverage, and the total size of the files needed for the EC number prediction.
DeepEC uses three convolutional neural networks (CNNs) as a major engine for the prediction of EC numbers, and also implements homology analysis for EC numbers if the three CNNs do not produce reliable EC numbers for a given protein sequence. DeepEC was developed by using a gold standard dataset covering 1,388,606 protein sequences and 4,669 EC numbers.
In particular, benchmarking studies of DeepEC and five other representative EC number prediction tools showed that DeepEC made the most precise and fastest predictions for EC numbers. DeepEC also required the smallest disk space for implementation, which makes it an ideal third-party software component.
Furthermore, DeepEC was the most sensitive in detecting enzymatic function loss as a result of mutations in domains/binding site residue of protein sequences; in this comparative analysis, all the domains or binding site residue were substituted with L-alanine residue in order to remove the protein function, which is known as the L-alanine scanning method.
This study was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 20, 2019, entitled “Deep learning enables high-quality and high-throughput prediction of enzyme commission numbers.”
“DeepEC can be used as an independent tool and also as a third-party software component in combination with other computational platforms that examine metabolic reactions. DeepEC is freely available online,” said Professor Kim.
Distinguished Professor Lee said, “With DeepEC, it has become possible to process ever-increasing volumes of protein sequence data more efficiently and more accurately.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation of Korea. This work was also funded by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean government, the Ministry of Science and ICT.
Profile:
-Professor Hyun Uk Kim (ehukim@kaist.ac.kr)
https://sites.google.com/view/ehukim
Department of Chemical and Biomolecular Engineering
-Distinguished Professor Sang Yup Lee (leesy@kaist.ac.kr)
Department of Chemical and Biomolecular Engineering
http://mbel.kaist.ac.kr
2019.07.09 View 37403 -
KAIST-KU Joint Research Center Opens
The Joint Research Center partnering KAIST and Khalifa University has been completed and the opening of the KAIST center was held on July 5, 2019, following the opening at Khalifa in April.
The joint research center will explore the most impactful technologies that will change people’s lives in the face of the new industrial environment brought about by the Fourth Industrial Revolution. The breakthroughs include smart transportation and smart healthcare such as wireless electric vehicles, unmanned vehicles, and wearable healthcare devices. The two institutions signed an MOU on the Joint Research Agreement on the Technology Development for the Fourth Industrial Revolution in 2018.
This is the second phase of collaboration following the partnership agreement that was signed in 2010 between the two institutions, which aimed to provide the best science and technology education as well as develop nuclear energy in the UAE.
The Khalifa University delegation, headed by Executive Vice President Arif Sultan Al Hammadi and Senior Vice President of Research and Development Steven Griffiths, flew in to attend the ceremony at KAIST. President Sung-Chul Shin, Vice President for Research Hyun Wook Park, Vice President for Planning and Budget Su-chan Chae, Associate Vice President of the International Office Man-Sung Yim joined and Co-Directors of the Joint Research Center Daniel Choi from Khalifa and Jong-Hyun Kim from KAIST also participated in the opening ceremony.
2019.07.06 View 7432 -
Wearable Robot 'WalkON Suit' Off to Cybathlon 2020
Standing upright and walking alone are very simple but noble motions that separate humans from many other creatures. Wearable and prosthetic technologies have emerged to augment human function in locomotion and manipulation. However, advances in wearable robot technology have been especially momentous to Byoung-Wook Kim, a triplegic for 22 years following a devastating car accident.
Kim rejoiced after standing upright and walking again by putting on the ‘WalkON Suit,’ the wearable robot developed by Professor Kyoungchul Kong’s team. Even more, Kim won third prize in the powered exoskeleton race at Cybathlon 2016, an international cyborg Olympics hosted by ETH Zurich.
Now Kim and Professor Kong’s team are all geared up for the Cybathlon Championship 2020. Professor Kong and his startup, Angel Robotics, held a kickoff ceremony for Cybathlon 2020 at KAIST on June 24. The 2020 championship will take place in Switzerland.
Only pilots with complete paralysis of the legs resulting from spinal cord injuries are eligible to participate in the Cybathlon, which takes place every four years. Pilots compete against each other while completing everyday tasks using technical assistance systems in six different disciplines: a brain-computer interface race, a functional electrical stimulation bike race, a powered arm prosthesis race, a powered leg prosthesis race, a powered exoskeleton race, and a powered wheelchair race. The 2016 championship drew 66 pilots from 56 teams representing 25 countries.
In the powered exoskeleton race, pilots complete everyday activities such as getting up from a sofa and overcoming obstacles such as stairs, ramps, or slopes and up to four pilots compete simultaneously on tracks to solve six tasks; and the pilot that solves the most tasks in the least amount of time wins the race.
(Kim, a triplegic for 22 years demonstrates walking and climbing the stairs (below photo) wearing the WalkOn Suit during the media day on June 21 at KAIST.)
Kim, who demonstrated walking and climbing the stairs wearing the WalkON Suit during the media day for the Cybathlon 2020 kickoff ceremony on June 21 at KAIST, said, “I have been confined to a wheelchair for more than 20 years. I am used to it so I feel like the wheelchair is one of my body parts. Actually, I don’t feel any big difficulties in doing everyday tasks in wheelchair. But whenever I face the fact that I will never be able to stand up with my own two legs again, I am so devastated.” He continued, “I still remember the day when I stood up with my own two legs by myself after 22 years. It was beyond description.”
The market for wearable robots, especially for exoskeleton robots, is continuing to grow as the aging population has been a major challenge in almost every advanced country. The global market for these robots expects to see annual growth of 41.2% to 8.3 billion US dollars by 2025. Healthcare wearable robots for the elderly and rehabilitation take up the half of the market share followed by wearable robots for industrial and defense purposes.
Professor Kong from the Department of Mechanical Engineering and his colleagues have developed two wearable robot systems in 2014: The "WalkON Suit" for complete paraplegics and “Angel Suit” for those with partial impairment in walking ability such as the elderly and rehabilitation patients.
Professor Kong said after 15 years of basic research, the team is now able to develop its own distinct technologies. He said their robots are powered by non-resistant precision drives with algorithms recognizing the user’s moving intention. Incorporated with prosthetic devices technology from the Severance Rehabilitation Hospital, their control technology has led to the production of a customizable robot suit optimized for each user’s physical condition.
The WalkON Suit, which boasts a maximum force of 250 Nm and maximum rotation speed of 45 RPM, gives the user high-energy efficiency modeled after the physiology of the human leg. It allows users to walk on flat ground and down stairs, climb up and down inclines, and sit and lie down. Currently the battery lasts five to six hours for locomotion and the approximate 25 kg of robot weight still remains a technical challenge to upgrade.
Professor Kong’s team has grafted AR glass technology into the WalkOn Suit that one of his pilots put on for the torch relay of the PyongChang Paralympics in 2018. His team is now upgrading the WalkON Suit 4.0 for next year’s competition. Severance Rehabilitation Hospital will help the seven pilots with their training.
Professor Kong said his goal is to make robots that can make people with disabilities much more independent. He stressed, “Wearable robots should be designed for each single user. We provide a very good graphical user interface so that we can design, check, and also verify our optimized design for users’ best performance.”
(Seven pilots and Professor Kong (fifth from left in second row) pose with guests who joined the Cybathlon 2020 kickoff ceremony. President Shin (fifth from right) made a congratulatory remarks during the ceremony.)
2019.06.25 View 40738 -
Hydrogen-Natural Gas Hydrates Harvested by Natural Gas
A hydrogen-natural gas blend (HNGB) can be a game changer only if it can be stored safely and used as a sustainable clean energy resource. A recent study has suggested a new strategy for stably storing hydrogen, using natural gas as a stabilizer. The research proposed a practical gas phase modulator based synthesis of HNGB without generating chemical waste after dissociation for the immediate service.
The research team of Professor Jae Woo Lee from the Department of Chemical and Biomolecular Engineering in collaboration with the Gwangju Institute of Science and Technology (GIST) demonstrated that the natural gas modulator based synthesis leads to significantly reduced synthesis pressure simultaneously with the formation of hydrogen clusters in the confined nanoporous cages of clathrate hydrates. This approach minimizes the environmental impact and reduces operation costs since clathrate hydrates do not generate any chemical waste in both the synthesis and decomposition processes.
For the efficient storage and transportation of hydrogen, numerous materials have been investigated. Among others, clathrate hydrates offer distinct benefits. Clathrate hydrates are nanoporous inclusion compounds composed of a 3D network of polyhedral cages made of hydrogen-bonded ‘host’ water molecules and captured ‘guest’ gas or liquid molecules.
In this study, the research team used two gases, methane and ethane, which have lower equilibrium conditions compared to hydrogen as thermodynamic stabilizers. As a result, they succeeded in stably storing the hydrogen-natural gas compound in hydrates. According to the composition ratio of methane and ethane, structure I or II hydrates can be formed, both of which can stably store hydrogen-natural gas in low-pressure conditions.
The research team found that two hydrogen molecules are stored in small cages in tuned structure I hydrates, while up to three hydrogen molecules can be stored in both small and large cages in tuned structure II hydrates. Hydrates can store gas up to about 170-times its volume and the natural gas used as thermodynamic stabilizers in this study can also be used as an energy source.
The research team developed technology to produce hydrates from ice, produced hydrogen-natural gas hydrates by substitution, and successfully observed that the tuning phenomenon only occurs when hydrogen is involved in hydrate formation from the start for both structures of hydrates.
They expect that the findings can be applied to not only an energy-efficient gas storage material, but also a smart platform to utilize hydrogen natural gas blends, which can serve as a new alternative energy source with targeted hydrogen contents by designing synthetic pathways of mixed gas hydrates.
The research was published online in Energy Storage Materials on June 6, with the title ‘One-step formation of hydrogen clusters in clathrate hydrates stabilized via natural gas blending’.
Professor Lee said, “HNGB will utilize the existing natural gas infrastructure for transportation, so it is very likely that we can commercialize this hydrate system. We are investigating the kinetic performance through a follow-up strategy to increase the volume of gas storage.
This study was funded by the National Research Foundation of Korea and BK21 plus program.
(Figure1. Schematics showing the storage method for hydrogen in a natural gas hydrate using a substitution method and storage method directly from ice to a hydrogen-natural gas hydrate.)
(Figure 2. Artificially synthesized and dissociated hydrogen-natural gas hydrates. The Raman spectra of tuned sI and sII hydrate showing the hydrogen clusters in each cage.)
2019.06.21 View 41414 -
Real-Time Analysis of MOF Adsorption Behavior
Researchers have developed a technology to analyze the adsorption behavior of molecules in each individual pore of a metal organic framework (MOF). This system has large specific surface areas, allowing for the real-time observation of the adsorption process of an MOF, a new material effective for sorting carbon dioxide, hydrogen, and methane.
Accurate measurements and assessments of gas adsorption isotherms are important for characterizing porous materials and developing their applications. The existing technology is only able to measure the amount of gas molecules adsorbed to the material, without directly observing the adsorption behavior.
The research team led by Professor Jeung Ku Kang from the Graduate School of Energy, Environment, Water and Sustainability (EEWS) prescribed a real time gas adsorption crystallography system by integrating an existing X-ray diffraction (XRD) measurement device that can provide structural information and a gas adsorption measurement device.
Specifically, the system allowed the observation of a mesoporous MOF that has multiple pores rather than a single pore structure. The research team categorized the adsorption behaviors of MOF molecules by pore type, followed by observations and measurements, resulting in the identification of a stepwise adsorption process that was previously not possible to analyze.
Further, the team systematically and quantitatively analyzed how the pore structure and the type of adsorption molecule affect the adsorption behavior to suggest what type of MOF structure is appropriate as a storage material for each type of adsorption behavior.
Professor Kang said, “We quantitatively analyzed each pore molecule in real time to identify the effects of chemical and structural properties of pores on adsorption behavior.” He continued, “By understanding the real-time adsorption behavior of molecules at the level of the pores that form the material, rather than the whole material, we will be able to apply this technology to develop a new high-capacity storage material.”
This research was published in Nature Chemistry online on May 13, 2019 under the title ‘Isotherms of Individual Pores by Gas Adsorption Crystallography’.
(Figure. Schematic illustration of molecules adsorbed on metal organic frameworks with different pores of various structures, where the In-situ X-ray crystallography has been developed to classify each pore structure and analyze the position of the molecule to determine the amount of molecules adsorbed to each pore.)
2019.06.18 View 39236 -
Play Games With No Latency
One of the most challenging issues for game players looks to be resolved soon with the introduction of a zero-latency gaming environment. A KAIST team developed a technology that helps game players maintain zero-latency performance. The new technology transforms the shapes of game design according to the amount of latency.
Latency in human-computer interactions is often caused by various factors related to the environment and performance of the devices, networks, and data processing. The term ‘lag’ is used to refer to any latency during gaming which impacts the user’s performance.
Professor Byungjoo Lee at the Graduate School of Culture Technology in collaboration with Aalto University in Finland presented a mathematical model for predicting players' behavior by understanding the effects of latency on players. This cognitive model is capable of predicting the success rate of a user when there is latency in a 'moving target selection' task which requires button input in a time constrained situation.
The model predicts the players’ task success rate when latency is added to the gaming environment. Using these predicted success rates, the design elements of the game are geometrically modified to help players maintain similar success rates as they would achieve in a zero-latency environment. In fact, this research succeeded in modifying the pillar heights of the Flappy Bird game, allowing the players to maintain their gaming performance regardless of the added latency.
Professor Lee said, "This technique is unique in the sense that it does not interfere with a player's gaming flow, unlike traditional methods which manipulate the game clock by the amount of latency. This study can be extended to various games such as reducing the size of obstacles in the latent computing environment.”
This research, in collaboration with Dr. Sunjun Kim from Aalto University and led by PhD candidate Injung Lee, was presented during the 2019 CHI Conference on Human Factors in Computing Systems last month in Glasgow in the UK.
This research was supported by the National Research Foundation of Korea (NRF) (2017R1C1B2002101, 2018R1A5A7025409), and the Aalto University Seed Funding Granted to the GamerLab respectively.
Figure 1. Overview of Geometric Compensation
Publication:
Injung Lee, Sunjun Kim, and Byungjoo Lee. 2019. Geometrically Compensating Effect of End-to-End Latency in Moving-Target Selection Games. In Proceedings of the 2019 CHI Conference on Human Factors in Computing Systems (CHI’19) . ACM, New York, NY, USA, Article 560, 12 pages. https://doi.org/10.1145/3290605.3300790
Video Material:
https://youtu.be/TTi7dipAKJs
Profile: Prof. Byungjoo Lee, MD, PhD
byungjoo.lee@kaist.ac.kr
http://kiml.org/
Assistant Professor
Graduate School of Culture Technology (CT)
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Injung Lee, PhD Candidate
edndn@kaist.ac.kr
PhD Candidate
Interactive Media Lab
Graduate School of Culture Technology (CT)
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon 34141, Korea
Profile: Postdoc. Sunjun Kim, MD, PhD
kuaa.net@gmail.com
Postdoctoral Researcher
User Interfaces Group
Aalto University
https://www.aalto.fi Espoo 02150, Finland
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2019.06.11 View 46722 -
Professor Cheol-Ho Jeong Honored with the DTU Lecturer of the Year
A KAIST alumnus and an associate professor at the Technical University of Denmark (DTU), Dr. Cheol-Ho Jeong was selected as the recipient of the Lecturer of the Year 2019 Award by DTU.
Professor Jeong received his B.S., M.Sc., and Ph. D. degrees from KAIST’s Department of Mechanical Engineering in August 2007 under the supervision of Professor Jeong-Guon Ih, and has been serving as an assistant followed by associate professor at DTU’s Department of Electrical Engineering since October 2007. His research covers wide arrays of architectural acoustics, environmental acoustics, psychoacoustics, and structural acoustics. Every year, the students at DTU nominate one or two lecturer(s) of the year. The award celebrates and honors the selected lecturers for showing great commitment not only to education itself, but also to their communication and engagement with the students.
This year, the DTU student union Polyteknisk Forening nominated Professor Jeong for his outstanding course evaluations for his excellent teaching over the years. One of the student testimonies for the award read, "Professor Jeong is one of the best teachers I have ever had at DTU. He is very humane and approachable."
The awards ceremony was held on May 3 at DTU during the 2019 Annual Commemoration Party and Professor Jeong was warmly congratulated by the Crown Prince Couple of Denmark. The other award was given to Professor Robert Madsen from DTU’s Chemistry department.
©Photo and Quote: Ulrik Jantzen, Büro Jantzen, Camilla Christiane Hermann.
2019.05.30 View 7368 -
'Think Out of the Box,' Team Circos Wins the P4G Innovation Sprint
<The winning team of the P4G Innovation Sprint poses with the Crown Prince of Denmark (sixth from the left in the first row) and President Shin (fifth from the left in the first row) during the awarding ceremony.>
Team Circos from KAIST and Denmark made a new sustainable business model for Hempel, a global coating supplier group in Denmark, and won the first prize at the P4G (the Partnership for Green Growth and Global Goals) Innovation Sprint held at KAIST’s Seoul campus on May 22. The six-member team was awarded one million KRW in prize money by the Crown Prince of Denmark. Two of winning team members have the privilege of traveling to visit Hempel in Denmark.
The winning team thought outside the box, inspired by box wine which reduced the sales price from traditional bottled wine. Six teams made up of members from different academic disciplines spent two nights and three days brainstorming ways to resolve the challenges of corporations such as Velux and Hempel from Denmark and SK from Korea.
The P4G Innovation Sprint is one of the events co-hosted by KAIST and Technological University of Denmark in celebration of the 60th anniversary of diplomatic relations establishment between Denmark and Korea and the 8th anniversary of the Green Growth Alliance between the two countries. The Crown Prince Couple also made a royal visit to Korea in honor of the 60th anniversary celebration and Green Growth Alliance between the two countries.
This Innovation Sprint aimed to develop young academics’ perspectives, skills, and talents for the next generation to better research the Sustainable Development Goals set by UN.
Three teams made their final five-minute pitches before the Crown Prince and President Sung-Chul
Shin and responded to questions from the four-member jury.
The Crown Prince of Denmark and President Shin both agreed that the collaborative and convergent ideas will address global problems.
The Crown Prince stressed in his congratulatory remarks the importance of partnership in this polarizing world to achieve sustainable improvements saying, “Partnerships are only possible to sustain through collaboration and hard work while staying curious, creative, and critical. " He also shared the special relationship with KAIST. His father-in-law Professor John Donaldson used to be a visiting professor of applied mathmatics at KAIST back in 2003.
President Shin added, “Collaboration across boundaries is most critical for responding to these issues. In that sense, this P4G Innovation Sprint is a shining example for demonstrating the collaborative efforts between teammates from diverse disciplines. When we work together and build convergent ideas, we will be more innovative and go further.”
<Winning team member Nicolai Thorball from DTU pitches at the final in the presence of the Crown Prince of Denmark and KAIST President Shin.>
“The canned packaging in the paint industry results in 40 times more carbon emission in the course of production. However, when using aluminum packaging which is recyclable, the waste amount will be cut dramatically,” pitched Nicolai Thorball from DTU on exchange at Seoul National University. Nicolai, whose major is environmental engineering, is one of two Danish students including Thomsen Xandra Flyvbjerg from the University of Southern Denmark. Flyvbjergy, majoring in business, is now on exchange at Sungkynkwan University.
“I am very glad to have the chance to understand the concept of the circular economy and green growth at the sprint. It was also very challenging to make ideation from so many ideas brainstormed,” said Dong-Eun Lee, a KAIST undergraduate from the Department of Biological Sciences. He said that he learned a lot from his two other teammates who are from the Program of Green Business & Policy at KAIST College of Business, Jae-Hee Park and Kyung-Hyun Kim. Juho Park majoring in mechanical engineering at KAIST was one of the team.
Circos’ solution for a sustainable model received acclaim from the jury members. DTU Senior Vice President Marianne Thellerson, one of jurors, claimed their model has very high market feasibility, saying, “Their idea could be commercialized right now into the market.” Professor Hee-Kyung Park from KAIST who helped participants’ ideation as one of four mentors said, “The winning team perfectly met all the components of the evaluation criteria, Solution, Acceleration, and Pitch.”
At this sprint, 10 students from Denmark and 29 KAIST students were divided into 6 teams and given the challenges of three companies. The Danish window facility company Velux presented its future glass window system and the paint company Hempel their circular economic new business model. SK challenged the students to help it become a global clean energy solution company. The event was based on a hacker blueprint that found the optimal solution to the topics proposed.
2019.05.23 View 9145 -
Engineered Microbial Production of Grape Flavoring
(Image 1: Engineered bacteria that produce grape flavoring.)
Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts.
Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway.
The authors tuned the bacterial metabolic pathway by optimizing the levels of AAMT1, the key enzyme in the process. To maximize production of MANT, the authors tested six strategies, including increasing the supply of a precursor compound and enhancing the availability of a co-substrate. The most productive strategy proved to be a two-phase extractive culture, in which MANT was extracted into a solvent. This strategy produced MANT on the scale of 4.47 to 5.74 grams per liter, a significant amount, considering that engineered microbes produce most natural products at a scale of milligrams or micrograms per liter.
According to the authors, the results suggest that MANT and other related molecules produced through industrial processes can be produced at scale by engineered microbes in a manner that would allow them to be marketed as natural one, instead of artificial one.
This study, featured at the Proceeding of the National Academy of Sciences of the USA on May 13, was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT.
(Image 2. Overview of the strategies applied for the microbial production of grape flavoring.)
2019.05.15 View 55310 -
Autophagy in Dendritic Cells Helps Anticancer Activity
Autophagy contributes to the homeostasis of a cell and recently another function of autophagy has been reported. A KAIST research team found that the autophagy of dendritic cells supports T-cell anticancer activity.
Autophagy is a process of maintaining cell homeostasis by removing cellular waste and damaged cellular organelles; nevertheless, its role in the presentation of phagocytized tumor-associated antigens remains vague.
Meanwhile, dendritic cells are the ones that recognize pathogens or cancer antigens, and induce immune responses in T cells. When cancer cells are killed by radiation or an anticancer drug, dendritic cells absorb and remove them and present antigens on their surface to transfer them to T-cells.
Professor Heung Kyu Lee from the Graduate School of Medical Science and Engineering and his team found that the autophagy of dendritic cells plays a key role in T-cell activation and they proposed the principles of enhancing anti-cancer effects.
Their experiments showed that T-cell activation of dendritic cells as well as anticancer immune response dropped when there is a deficiency of Atg5 (autophagy-related) in dendritic cells.
Interestingly, Atg5-deficient dendritic cells significantly elevated receptor CD36 on the surface of the cells, which increased the phagocytosis of apoptotic tumor cells yet restricted the activation of T-cells.
At this time, when introducing antibodies into the system in order to block the receptor CD36, the anti-tumor T-cell response increased substantially while tumor growth declined.
Professor Lee said, “This study allowed us to explore the role of autophagy in the anti-cancer immune response of T-cells. We look forward to developing targeted anti-cancer therapies using the receptor CD36.”
This research was published in Autophagy (10.1080/15548627.2019.1596493) on March 22, 2019.
Figure 1.Mechanism of autophagy in dendritic cells
Figure 2. A role of autophagy in dendritic cells
2019.05.13 View 51088