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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 24083 -
KAIST to Transfer Core Tech to Domestic Companies amid Japan's Export Curbs
< Associate Vice President Kyung-Cheol Choi of the Office of University-Industry Cooperation (OUIC) at KAIST >
KAIST will transfer four core technologies related to materials, parts, and equipment to domestic companies to help them combat the latest export curbs triggered by Korea’s removal from Japan’s ‘white list’ of preferential trade partners. In addition, KAIST’s five patented technologies in the field of artificial intelligence (AI) and materials and parts will also be transferred to the companies in order to reduce the reliance on Japan and achieve technological independence through the ‘localization’ of key technologies.
KAIST announced these university-industry cooperation promotion plans at the ‘2019 KAIST Core Tech Transfer Day Conference’ held in Seoul on September 17. More than 200 entrepreneurs and investors attended the briefing and on-site consulting sessions delivered by nine KAIST professors who led the development of the technologies.
The four technologies were presented at the conference as those that can replace Japanese technologies subject to the export curbs. They include:
1. ‘Transparent fluorinated polyimide with low thermal expansion’ developed by Professor Sang-Youl Kim of the Department of Chemistry
2. ‘A non-destructive electromagnetic performance testing system’ developed by Professor Jung-Ryul Lee of the Department of Aerospace Engineering
3. ‘A nanotechnology-based electrode material for use in advanced secondary batteries’ developed by Professor Do-Kyung Kim of the Department of Materials Science and Engineering
4. ‘A high-resolution photoresist’ developed by Professor Emeritus Jin-Baek Kim of the Department of Chemistry.
Of particular interest is the non-destructive electromagnetic performance testing system technology developed by Professor Jung-Ryul Lee. This new cost-effective technology enables tests that were impossible to carry out using conventional technologies and yields a cost reduction of more than 50 percent compared to foreign technologies.
By introducing Professor Do-Kyung Kim’s new electrode material technology, the efficiency of electric vehicles can be increased. As this technology uses relatively low-cost sodium ion batteries, industries can prepare for the possible jump from the more expensive lithium batteries currently being used.
Another five patented AI and materials and parts technologies disclosed at the conference include:
1. ‘Enhanced HTTP adaptive streaming with CNN-based super-resolution’ developed by Professor Dong-soo Han of the School of Electrical Engineering
2. ‘Method and apparatus of brain-computer interface design for estimating choice behavior and decision strategy’ developed by Professor Sang-Wan Lee of the Department of Bio and Brain Engineering
3. ‘Eco-friendly fabrication of metal oxide nanoparticles and fabrication of non-toxic polymer sunscreen ingredients by electron irradiation’ developed by Professor Sung-Oh Cho of the Department of Nuclear and Quantum Engineering
4. ‘High-density nanofiber yarn-based coloricmetric gas sensors’ developed by Professor Il-Doo Kim of the Department of Materials Science and Engineering
5. ‘Silicon-pocket energy storage electrode with high energy density and its manufacturing technology’ developed by Professor Jeung-Ku Kang of the Graduate school of EEWS.
The patented nanofiber-based coloricmetric gas sensor technology developed by Professor Il-Doo Kim allows for the diagnosis of diseases by only using the patient’s respiration. Due to its high productivity and processability, it is expected to be applied to various fields in the fast-growing disease diagnosis sensor market, which includes mobile devices and wearable sensors.
Moreover, Professor Dong-soo Han’s patented adaptive streaming technology attracted attention along with the ever-growing Over The Top (OTT) and Video On Demand (VOD) service markets, since it has significant potential for improving the streaming quality of videos and reducing costs for video providers.
Professor Kyung-Cheol Choi, the Associate Vice President of the Office of University-Industry Cooperation (OUIC) at KAIST, said, “KAIST OUIC and KAIST Advisors on Materials and Parts (KAMP) have been working tirelessly to help Korean companies cope with the recent Japanese export restrictions. KAIST’s efforts will enhance the competitiveness and growth of the Korean industry and economy, turning this national crisis into opportunity.”
(END)
2019.09.20 View 5909 -
Highly Uniform and Low Hysteresis Pressure Sensor to Increase Practical Applicability
< Professor Steve Park (left) and the First Author Mr. Jinwon Oh (right) >
Researchers have designed a flexible pressure sensor that is expected to have a much wider applicability. A KAIST research team fabricated a piezoresistive pressure sensor of high uniformity with low hysteresis by chemically grafting a conductive polymer onto a porous elastomer template.
The team discovered that the uniformity of pore size and shape is directly related to the uniformity of the sensor. The team noted that by increasing pore size and shape variability, the variability of the sensor characteristics also increases.
Researchers led by Professor Steve Park from the Department of Materials Science and Engineering confirmed that compared to other sensors composed of randomly sized and shaped pores, which had a coefficient of variation in relative resistance change of 69.65%, their newly developed sensor exhibited much higher uniformity with a coefficient of variation of 2.43%. This study was reported in Small as the cover article on August 16.
Flexible pressure sensors have been actively researched and widely applied in electronic equipment such as touch screens, robots, wearable healthcare devices, electronic skin, and human-machine interfaces. In particular, piezoresistive pressure sensors based on elastomer‐conductive material composites hold significant potential due to their many advantages including a simple and low-cost fabrication process.
Various research results have been reported for ways to improve the performance of piezoresistive pressure sensors, most of which have been focused on increasing the sensitivity. Despite its significance, maximizing the sensitivity of composite-based piezoresistive pressure sensors is not necessary for many applications. On the other hand, sensor-to-sensor uniformity and hysteresis are two properties that are of critical importance to realize any application.
The importance of sensor-to-sensor uniformity is obvious. If the sensors manufactured under the same conditions have different properties, measurement reliability is compromised, and therefore the sensor cannot be used in a practical setting.
In addition, low hysteresis is also essential for improved measurement reliability. Hysteresis is a phenomenon in which the electrical readings differ depending on how fast or slow the sensor is being pressed, whether pressure is being released or applied, and how long and to what degree the sensor has been pressed. When a sensor has high hysteresis, the electrical readings will differ even under the same pressure, making the measurements unreliable.
Researchers said they observed a negligible hysteresis degree which was only 2%. This was attributed to the strong chemical bonding between the conductive polymer and the elastomer template, which prevents their relative sliding and displacement, and the porosity of the elastomer that enhances elastic behavior.
“This technology brings forth insight into how to address the two critical issues in pressure sensors: uniformity and hysteresis. We expect our technology to play an important role in increasing practical applications and the commercialization of pressure sensors in the near future,” said Professor Park.
This work was conducted as part of the KAIST‐funded Global Singularity Research Program for 2019, and also supported by the KUSTAR‐KAIST Institute.
Figure 1. Image of a porous elastomer template with uniform pore size and shape (left), Graph showing high uniformity in the sensors’ performance (right).
Figure 2. Hysteresis loops of the sensor at different pressure levels (left), and after a different number of cycles (right).
Figure 3. The cover page of Small Journal, Volume 15, Issue 33.
Publication:
Jinwon Oh, Jin‐Oh Kim, Yunjoo Kim, Han Byul Choi, Jun Chang Yang, Serin Lee, Mikhail Pyatykh, Jung Kim, Joo Yong Sim, and Steve Park. 2019. Highly Uniform and Low Hysteresis Piezoresistive Pressure Sensors Based on Chemical Grafting of Polypyrrole on Elastomer Template with Uniform Pore Size. Small. Wiley-VCH Verlag GmbH & Co. KgaA, Weinheim, Germany, Volume No. 15, Issue No. 33, Full Paper No. 201901744, 8 pages. https://doi.org/10.1002/smll.201901744
Profile: Prof. Steve Park, MS, PhD
stevepark@kaist.ac.kr
http://steveparklab.kaist.ac.kr/
Assistant Professor
Organic and Nano Electronics Laboratory
Department of Materials Science and Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon 34141, Korea
Profile: Mr. Jinwon Oh, MS
jwoh1701@gmail.com
http://steveparklab.kaist.ac.kr/
Researcher
Organic and Nano Electronics Laboratory
Department of Materials Science and Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Prof. Jung Kim, MS, PhD
jungkim@kaist.ac.kr
http://medev.kaist.ac.kr/
Professor
Biorobotics Laboratory
Department of Mechanical Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Joo Yong Sim, PhD
jsim@etri.re.kr
Researcher
Bio-Medical IT Convergence Research Department
Electronics and Telecommunications Research Institute (ETRI)
https://www.etri.re.krDaejeon 34129, Korea
(END)
2019.08.19 View 25642 -
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 34480 -
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 38126 -
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 39780 -
Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.
The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates.
Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats.
The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass.
Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization.
To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced.
They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production.
“This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee.
This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17.
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 (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557).
(Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.)
# # #
Source:
Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5
Profile
Dr. Sang Yup Lee
leesy@kaist.ac.kr
Distinguished Professor at the Department of Chemical and Biomolecular Engineering
KAIST
2019.06.19 View 46366 -
Early Genome Catastrophes Can Cause Non-Smoking Lung Cancer
Some teenagers harbor catastrophic changes to their genomes that can lead to lung cancer later on in life, even if they never smoke
(Professor Young Seok Ju at the Graduate School of Medical Science and Engineering)
Catastrophic rearrangements in the genome occurring as early as childhood and adolescence can lead to the development of lung cancer in later years in non-smokers. This finding, published in Cell, helps explain how some non-smoking-related lung cancers develop.
Researchers at KAIST, Seoul National University and their collaborators confirmed that gene fusions in non-smokers mostly occur early on, sometimes as early as childhood or adolescence, and on average about three decades before cancer is diagnosed. The study showed that these mutant lung cells, harboring oncogenic seeds, remain dormant for several decades until a number of further mutations accumulate sufficiently for progression into cancer. This is the first study to reveal the landscape of genome structural variations in lung adenocarcinoma.
Lung cancer is the leading cause of cancer-related deaths worldwide, and lung adenocarcinoma is its most common type. Most lung adenocarcinomas are associated with chronic smoking, but about a fourth develop in non-smokers. Precisely what happens in non-smokers for this cancer to develop is not clearly understood.
Researchers analyzed the genomes of 138 lung adenocarcinoma patients, including smokers and non-smokers, with whole-genome sequencing technologies. They explored DNA damage that induced neoplastic transformation.
Lung adenocarcinomas that originated from chronic smoking, referred to as signature 4-high (S4-high) cancers in the study, showed several distinguishing features compared to smoking-unrelated cancers (S4-low).
People in the S4-high group were largely older, men and had more frequent mutations in a cancer-related gene called KRAS. Cancer genomes in the S4-high group were hypermutated with simple mutational classes, such as the substitution, insertion, or deletion of a single base, the building block of DNA.
But the story was very different in the S4-low group. Generally, mutational profiles in this group were much more silent than the S4-high group. However, all cancer-related gene fusions, which are abnormally activated from the merging of two originally separate genes, were exclusively observed in the S4-low group.
The patterns of genomic structural changes underlying gene fusions suggest that about three in four cases of gene fusions emerged from a single cellular crisis causing massive genomic fragmentation and subsequent imprecise repair in normal lung epithelium.
Most strikingly, these major genomic rearrangements, which led to the development of lung adenocarcinoma, are very likely to be acquired decades before cancer diagnosis. The researchers used genomic archaeology techniques to trace the timing of when the catastrophes took place.
Researchers started this study seven years ago when they discovered the expression of the KIF5B-RET gene fusion in lung adenocarcinoma for the first time. Professor Young-Seok Ju, co-lead author from the Graduate School of Medical Science and Engineering at KAIST says, “It is remarkable that oncogenesis can begin by a massive shattering of chromosomes early in life. Our study immediately raises a new question: What induces the mutational catastrophe in our normal lung epithelium.”
Professor Young Tae Kim, co-lead author from Seoul National University says, “We hope this work will help us get one step closer to precision medicine for lung cancer patients.”
The research team plans to further focus on the molecular mechanisms that stimulate complex rearrangements in the body, through screening the genomic structures of fusion genes in other cancer types.
This study was supported by the National Research Foundation of Korea (NRF), Korea Health Industry Development Institute (KHIDI), Suh Kyungbae Foundation, the College of Medicine Research Foundations at Seoul National University and others.
Figure.
(Smoking-unrelated oncogenesis of lung cancers by gene fusions)
Publication.
Jake June-Koo Lee, Seongyeol Park et al., Tracing Oncogene Rearrangements in the Mutational History of Lung Adenocarcinoma
Cell 177, June 13 2019, online publication ahead of print at May 30, 2019
https://doi.org/10.1016/j.cell.2019.05.013
Profile: Prof Young Seok Ju, MD, PhD
ysju@kaist.ac.kr
http://julab.kaist.ac.kr
Associate Professor
Graduate School of Medical Science and Engineering (GSMSE)
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon 34141, Korea
Profile: Prof Young Tae Kim, MD, PhD
ytkim@snu.ac.kr
Professor
Seoul National University Cancer Research Institute
Department of Thoracic and Cardiovascular Surgery
Seoul National University Hospital Seoul 03080, Korea
2019.05.31 View 54791 -
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 5853 -
'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.
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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.)
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KAIST 2019 Commencement at a Glance
(KAIST 2019 Commencement Ceremony)
This year, KAIST awarded a total of 2,705 degrees: 654 PhD degrees, 1,255 master’s degrees, and 796 bachelor’s degrees. Including this year’s numbers, KAIST has conferred a total of 63,830 degrees since its foundation in 1971.
Parents, family, and friends came to campus to congratulate the graduates with big smiles and hugs. Faculty and staff members also attended the ceremony to celebrate their graduation. This year, distinguished guests including National Assembly Member Kyung-Jin Kim and Vice Minister for Science, Technology and Innovation Dae-sik came to celebrate the day with the KAIST community.
During the commencement, KAIST also announced the recipients of its undergraduate academic awards. The Minister of Science and ICT Award was won by Do-Yoon Kim from the Department of Aerospace Engineering, the KAIST Board of Trustee Chairperson Award went to Se-rin Lee from the Department of Materials Science and Engineering, the KAIST Presidential Award was won by Hee-Ju Kim from the Department of Physics, the KAIST Alumni Association President Award went to Hyeon-Seong Park from the School of Electrical Engineering, and finally the KAIST Development Foundation Chairperson Award was won by Gyeong-Hoon Lee from the Department of Mathematical Sciences.
This year’s valedictorian Eun-Seok Jeong from the School of Computing said, “I believe that we are able to stand here today because we challenged ourselves to confront our shortcomings and our uncertainty. If we continue to develop, we will become a better person than we were yesterday.”
(KAIST President Sung-Chul Shin and Woo-Seok Jeong, '19 PhD in Aerospace Engineering)
As a KAIST alumnus and fellow scientist, President Sung-Chul Shin offered his congratulations and emphasized that graduates should continue to pursue the C³ spirit. “In this age of great transformation, embrace challenges and exercise creativity as you have learnt through your education and research at KAIST. And keep in mind the importance of caring for others. Please remember that challenge and creativity will have more meaning if rendered with a caring spirit,” he said.
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