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Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease
Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week.
Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear.
Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing.
The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases.
The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD.
Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins.
“Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee.
The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease.
(Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.)
(Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.)
(Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
2019.07.19 View 34223 -
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 34544 -
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 9783 -
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 38198 -
Anti-drone Technology for Anti-Terrorism Applications
(from top right clockwise: Professor Yongdae Kim,
PhD Candidates Yujin Kwon, Juhwan Noh, Hocheol Shin, and Dohyun Kim)
KAIST researchers have developed anti-drone technology that can hijack other drones by spoofing its location using fake GPS signals. This technology can safely guide a drone to a desired location without any sudden change in direction in emergency situations, and thus respond effectively to dangerous drones such as those intending to carry out acts of terrorism.
Advancements in the drone industry have led to the wider use of drones in our daily lives in areas of reconnaissance, searching and rescuing, disaster prevention and response, and delivery services. At the same time, there has also been a growing concern about privacy, safety, and security issues regarding drones, especially those arising from intrusion into private property and secure facilities. Therefore, the anti-drone industry is rapidly expanding to detect and respond to this possible drone invasion.
The current anti-drone systems used in airports and other key locations utilize electronic jamming signals, high-power lasers, or nets to neutralize drones. For example, drones trespassing on airports are often countered with simple jamming signals that can prevent the drones from moving and changing position, but this may result in a prolonged delay in flight departures and arrivals at the airports. Drones used for terrorist attacks – armed with explosives or weapons – must also be neutralized a safe distance from the public and vital infrastructure to minimize any damage.
Due to this need for a new anti-drone technology to counter these threats, a KAIST research team led by Professor Yongdae Kim from the School of Electrical Engineering has developed technology that securely thwarts drones by tricking them with fake GPS signals.
Fake GPS signals have been used in previous studies to cause confusion inside the drone regarding its location, making the drone drift from its position or path. However, such attack tactics cannot be applied in GPS safety mode. GPS safety mode is an emergency mode that ensures drone safety when the signal is cut or location accuracy is low due to a fake GPS signals. This mode differs between models and manufacturers.
Professor Kim’s team analyzed the GPS safety mode of different drone models made from major drone manufacturers such as DJI and Parrot, made classification systems, and designed a drone abduction technique that covers almost all the types of drone GPS safety modes, and is universally applicable to any drone that uses GPS regardless of model or manufacturer. The research team applied their new technique to four different drones and have proven that the drones can be safely hijacked and guided to the direction of intentional abduction within a small margin of error.
Professor Kim said, “Conventional consumer drones equipped with GPS safety mode seem to be safe from fake GPS signals, however, most of these drones are able to be detoured since they detect GPS errors in a rudimentary manner.” He continued, “This technology can contribute particularly to reducing damage to airports and the airline industry caused by illegal drone flights.”
The research team is planning to commercialize the developed technology by applying it to existing anti-drone solutions through technology transfer.” This research, featured in the ACM Transactions on Privacy and Security (TOPS) on April 9, was supported by the Defense Acquisition Program Administration (DAPA) and the Agency for Defense Development (ADD).
Image 1.
Experimental environment in which a fake GPS signal was produced from a PC and injected into the drone signal using directional antennae
Publication:
Juhwan Noh, Yujin Kwon, Yunmok Son, Hocheol Shin, Dohyun Kim, Jaeyeong Choi, and Yongdae Kim. 2019. Tractor Beam: Safe-hijacking of Consumer Drones with Adaptive GPS Spoofing. ACM Transactions on Privacy and Security. New York, NY, USA, Vol. 22, No. 2, Article 12, 26 pages. https://doi.org/10.1145/3309735
Profile: Prof. Yongdae Kim, MS, PhD
yongdaek@kaist.ac.kr
https://www.syssec.kr/
Professor
School of Electrical Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Juhwan Noh, PhD Candidate
juhwan@kaist.ac.kr
PhD Candidate
System Security (SysSec) Lab
School of Electrical Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
(END)
2019.06.25 View 42346 -
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 39813 -
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 46426 -
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 54837 -
Professor Yim Decorated with the Chongjo Order of Merit
Professor Yong-Taek Yim from the Department of Mechanical Engineering was awarded the highest order of merit, the “Chongjo Keunjong Medal,” bestowed to public officials by the government in celebration of Invention Day on May 27.
Professor Yim was recognized for his innovative achievements to increase royalty income by introducing an IP-based management system at the Korean Institute of Machinery & Materials. He served as the president of KIMM for three years from 2014.
His idea led to new approaches to help explore diverse revenue creating sources such as dividend earnings and share sales, apart from simply relying on technology transfer fees. His efforts to disseminate the in-house R&D results also led to the foundation of six tech-based startups and spinoffs, which generated 11.2 billion KRW in sales. He also helped set up three spinoffs abroad.
Professor Yim said, “I pushed employee invention as a new value creator at KIMM. I thank each and every researcher and staff member at KIMM who worked so hard to create such an innovative IP-based R&D environment.”
2019.05.28 View 5817 -
5 Biomarkers for Overcoming Colorectal Cancer Drug Resistance Identified
< Professor Kwang-Hyun Cho's Team >
KAIST researchers have identified five biomarkers that will help them address resistance to cancer-targeting therapeutics. This new treatment strategy will bring us one step closer to precision medicine for patients who showed resistance.
Colorectal cancer is one of the most common types of cancer worldwide. The number of patients has surpassed 1 million, and its five-year survival rate significantly drops to about 20 percent when metastasized. In Korea, the surge of colorectal cancer has been the highest in the last 10 years due to increasing Westernized dietary patterns and obesity. It is expected that the number and mortality rates of colorectal cancer patients will increase sharply as the nation is rapidly facing an increase in its aging population.
Recently, anticancer agents targeting only specific molecules of colon cancer cells have been developed. Unlike conventional anticancer medications, these selectively treat only specific target factors, so they can significantly reduce some of the side-effects of anticancer therapy while enhancing drug efficacy.
Cetuximab is the most well-known FDA approved anticancer medication. It is a biomarker that predicts drug reactivity and utilizes the presence of the ‘KRAS’ gene mutation. Cetuximab is prescribed to patients who don’t carry the KRAS gene mutation.
However, even in patients without the KRAS gene mutation, the response rate of Cetuximab is only about fifty percent, and there is also resistance to drugs after targeted chemotherapy. Compared with conventional chemotherapy alone, the life expectancy only lasts five months on average.
In research featured in the FEBS Journal as the cover paper for the April 7 edition, the KAIST research team led by Professor Kwang-Hyun Cho at the Department of Bio and Brain Engineering presented five additional biomarkers that could increase Cetuximab responsiveness using systems biology approach that combines genomic data analysis, mathematical modeling, and cell experiments. The experimental inhibition of newly discovered biomarkers DUSP4, ETV5, GNB5, NT5E, and PHLDA1 in colorectal cancer cells has been shown to overcome Cetuximab resistance in KRAS-normal genes. The research team confirmed that when suppressing GNB5, one of the new biomarkers, it was shown to overcome resistance to Cetuximab regardless of having a mutation in the KRAS gene.
Professor Cho said, “There has not been an example of colorectal cancer treatment involving regulation of the GNB5 gene.” He continued, “Identifying the principle of drug resistance in cancer cells through systems biology and discovering new biomarkers that could be a new molecular target to overcome drug resistance suggest real potential to actualize precision medicine.”
This study was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT (2017R1A2A1A17069642 and 2015M3A9A7067220).
Image 1. The cover of FEBS Journal for April 2019
2019.05.27 View 57459 -
Professor Yim Appointed As Associate Editor of Nuclear Technology
Professor Man-Sung Yim from the Department of Nuclear and Quantum Engineering was appointed as the associate editor (for the Asian region) of Nuclear Technology ― a leading international research journal of the American Nuclear Society. Professor Yim will serve his term for three years from May 2019.
The American Nuclear Society, established in 1954, is comprised of more than 11,000 global members and aims to advance nuclear science, engineering, and technology while supporting the peaceful and beneficial applications of nuclear energy. Since its first publication in 1971, Nuclear Technology has been a representative journal of the society, reporting state-of-the-art information on all phases of the practical applications of nuclear technology.
Professor Yim is being recognized worldwide for his pioneering nuclear education, research, and policy studies in the fields of non-proliferation, safeguards for severe accident management, and waste management. He served as the head professor of the Department of Nuclear and Quantum Engineering and established the Nonproliferation Education and Research Center (NEREC) at KAIST.
Professor Yim remarked, “Asia has an important role to play at the forefront of the world’s nuclear research considering that nuclear development is most actively being carried out in the Asian region these days.”
2019.05.17 View 6248 -
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 52778