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A Study Shows Reactive Electrolyte Additives Improve Lithium Metal Battery Performance
Stable electrode-electrolyte interfaces constructed by fluorine- and nitrogen-donating ionic additives provide an opportunity to improve high-performance lithium metal batteries A research team showed that electrolyte additives increase the lifetime of lithium metal batteries and remarkably improve the performance of fast charging and discharging. Professor Nam-Soon Choi’s team from the Department of Chemical and Biomolecular Engineering at KAIST hierarchized the solid electrolyte interphase to make a dual-layer structure and showed groundbreaking run times for lithium metal batteries. The team applied two electrolyte additives that have different reduction and adsorption properties to improve the functionality of the dual-layer solid electrolyte interphase. In addition, the team has confirmed that the structural stability of the nickel-rich cathode was achieved through the formation of a thin protective layer on the cathode. This study was reported in Energy Storage Materials. Securing high-energy-density lithium metal batteries with a long lifespan and fast charging performance is vital for realizing their ubiquitous use as superior power sources for electric vehicles. Lithium metal batteries comprise a lithium metal anode that delivers 10 times higher capacity than the graphite anodes in lithium-ion batteries. Therefore, lithium metal is an indispensable anode material for realizing high-energy rechargeable batteries. However, undesirable reactions among the electrolytes with lithium metal anodes can reduce the power and this remains an impediment to achieving a longer battery lifespan. Previous studies only focused on the formation of the solid electrolyte interphase on the surface of the lithium metal anode. The team designed a way to create a dual-layer solid electrolyte interphase to resolve the instability of the lithium metal anode by using electrolyte additives, depending on their electron accepting ability and adsorption tendencies. This hierarchical structure of the solid electrolyte interphase on the lithium metal anode has the potential to be further applied to lithium-alloy anodes, lithium storage structures, and anode-free technology to meet market expectations for electrolyte technology. The batteries with lithium metal anodes and nickel-rich cathodes represented 80.9% of the initial capacity after 600 cycles and achieved a high Coulombic efficiency of 99.94%. These remarkable results contributed to the development of protective dual-layer solid electrolyte interphase technology for lithium metal anodes. Professor Choi said that the research suggests a new direction for the development of electrolyte additives to regulate the unstable lithium metal anode-electrolyte interface, the biggest hurdle in research on lithium metal batteries. She added that anode-free secondary battery technology is expected to be a game changer in the secondary battery market and electrolyte additive technology will contribute to the enhancement of anode-free secondary batteries through the stabilization of lithium metal anodes. This research was funded by the Technology Development Program to Solve Climate Change of the National Research Foundation in Korea funded by the Ministry of Science, ICT & Future Planning and the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy, and Hyundai Motor Company. - PublicationSaehun Kim, Sung O Park, Min-Young Lee, Jeong-A Lee, Imanuel Kristanto, Tae Kyung Lee, Daeyeon Hwang, Juyoung Kim, Tae-Ung Wi, Hyun-Wook Lee, Sang Kyu Kwak, and NamSoon Choi, “Stable electrode-electrolyte interfaces constructed by fluorine- and nitrogen-donating ionic additives for high-performance lithium metal batteries,” Energy Storage Materials,45, 1-13 (2022), (doi: https://doi.org/10.1016/j.ensm.2021.10.031) - ProfileProfessor Nam-Soon ChoiEnergy Materials LaboratoryDepartment of Chemical and Biomolecular EngineeringKAIST
2021.12.16
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Connecting the Dots to Find New Treatments for Breast Cancer
Systems biologists uncovered new ways of cancer cell reprogramming to treat drug-resistant cancers Scientists at KAIST believe they may have found a way to reverse an aggressive, treatment-resistant type of breast cancer into a less dangerous kind that responds well to treatment. The study involved the use of mathematical models to untangle the complex genetic and molecular interactions that occur in the two types of breast cancer, but could be extended to find ways for treating many others. The study’s findings were published in the journal Cancer Research. Basal-like tumours are the most aggressive type of breast cancer, with the worst prognosis. Chemotherapy is the only available treatment option, but patients experience high recurrence rates. On the other hand, luminal-A breast cancer responds well to drugs that specifically target a receptor on their cell surfaces, called estrogen receptor alpha (ERα). KAIST systems biologist Kwang-Hyun Cho and colleagues analyzed the complex molecular and genetic interactions of basal-like and luminal-A breast cancers to find out if there might be a way to switch the former to the latter and give patients a better chance to respond to treatment. To do this, they accessed large amounts of cancer and patient data to understand which genes and molecules are involved in the two types. They then input this data into a mathematical model that represents genes, proteins and molecules as dots and the interactions between them as lines. The model can be used to conduct simulations and see how interactions change when certain genes are turned on or off. “There have been a tremendous number of studies trying to find therapeutic targets for treating basal-like breast cancer patients,” says Cho. “But clinical trials have failed due to the complex and dynamic nature of cancer. To overcome this issue, we looked at breast cancer cells as a complex network system and implemented a systems biological approach to unravel the underlying mechanisms that would allow us to reprogram basal-like into luminal-A breast cancer cells.” Using this approach, followed by experimental validation on real breast cancer cells, the team found that turning off two key gene regulators, called BCL11A and HDAC1/2, switched a basal-like cancer signalling pathway into a different one used by luminal-A cancer cells. The switch reprograms the cancer cells and makes them more responsive to drugs that target ERα receptors. However, further tests will be needed to confirm that this also works in animal models and eventually humans. “Our study demonstrates that the systems biological approach can be useful for identifying novel therapeutic targets,” says Cho. The researchers are now expanding its breast cancer network model to include all breast cancer subtypes. Their ultimate aim is to identify more drug targets and to understand the mechanisms that could drive drug-resistant cells to turn into drug-sensitive ones. This work was supported by the National Research Foundation of Korea, the Ministry of Science and ICT, Electronics and Telecommunications Research Institute, and the KAIST Grand Challenge 30 Project. -Publication Sea R. Choi, Chae Young Hwang, Jonghoon Lee, and Kwang-Hyun Cho, “Network Analysis Identifies Regulators of Basal-like Breast Cancer Reprogramming and Endocrine TherapyVulnerability,” Cancer Research, November 30. (doi:10.1158/0008-5472.CAN-21-0621) -ProfileProfessor Kwang-Hyun ChoLaboratory for Systems Biology and Bio-Inspired EngineeringDepartment of Bio and Brain EngineeringKAIST
2021.12.07
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A Genetic Change for Achieving a Long and Healthy Life
Researchers identified a single amino acid change in the tumor suppressor protein in PTEN that extends healthy periods while maintaining longevity Living a long, healthy life is everyone’s wish, but it is not an easy one to achieve. Many aging studies are developing strategies to increase health spans, the period of life spent with good health, without chronic diseases and disabilities. Researchers at KAIST presented new insights for improving the health span by just regulating the activity of a protein. A research group under Professor Seung-Jae V. Lee from the Department of Biological Sciences identified a single amino acid change in the tumor suppressor protein phosphatase and tensin homolog (PTEN) that dramatically extends healthy periods while maintaining longevity. This study highlights the importance of the well-conserved tumor suppressor protein PTEN in health span regulation, which can be targeted to develop therapies for promoting healthy longevity in humans. The research was published in Nature Communications on September 24, 2021. Insulin and insulin-like growth factor-1 (IGF-1) signaling (IIS) is one of the evolutionarily conserved aging-modulatory pathways present in life forms ranging from tiny roundworms to humans. The proper reduction of IIS leads to longevity in animals but often causes defects in multiple health parameters including impaired motility, reproduction, and growth. The research team found that a specific amino acid change in the PTEN protein improves health status while retaining the longevity conferred by reduced IIS. They used the roundworm C. elegans, an excellent model animal that has been widely used for aging research, mainly because of its very short normal lifespan of about two to three weeks. The PTEN protein is a phosphatase that removes phosphate from lipids as well as proteins. Interestingly, the newly identified amino acid change delicately recalibrated the IIS by partially maintaining protein phosphatase activity while reducing lipid phosphatase activity. As a result, the amino acid change in the PTEN protein maintained the activity of the longevity-promoting transcription factor Forkhead Box O (FOXO) protein while restricting the detrimental upregulation of another transcription factor, NRF2, leading to long and healthy life in animals with reduced IIS. Professor Lee said, “Our study raises the exciting possibility of simultaneously promoting longevity and health in humans by slightly tweaking the activity of one protein, PTEN.” This work was supported by the MInistry of Science and ICT through the National Research Foundation of Korea. -Publication:Hae-Eun H. Park, Wooseon Hwang, Seokjin Ham, Eunah Kim, Ozlem Altintas, Sangsoon Park, Heehwa G. Son, Yujin Lee, Dongyeop Lee, Won Do Heo, and Seung-Jae V. Lee. 2021. “A PTEN variant uncouples longevity from impaired fitness in Caenorhabditis elegans with reduced insulin/IGF-1 signaling,” Nature Communications, 12(1), 5631. (https://doi.org/10.1038/s41467-021-25920-w) -ProfileProfessor Seung-Jae V. LeeMolecular Genetics of Aging LaboratoryDepartment of Biological Sciences KAIST
2021.11.19
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Two Researchers Designated as SUHF Fellows
Professor Taeyun Ku from the Graduate School of Medical Science and Engineering and Professor Hanseul Yang from the Department of Biological Sciences were nominated as 2021 fellows of the Suh Kyungbae Foundation (SUHF). SUHF selected three young promising scientists from 53 researchers who are less than five years into their careers. A panel of judges comprised of scholars from home and abroad made the final selection based on the candidates’ innovativeness and power to influence. Professor You-Bong Hyun from Seoul National University also won the fellowship. Professor Ku’s main topic is opto-connectomics. He will study ways to visualize the complex brain network using innovative technology that transforms neurons into optical elements. Professor Yang will research the possibility of helping patients recover from skin diseases or injuries without scars by studying spiny mouse genes. SUHF was established by Amorepacific Group Chairman Suh Kyungbae in 2016 with 300 billion KRW of his private funds. Under the vision of ‘contributing to humanity by supporting innovative discoveries of bioscience researchers,’ the foundation supports promising Korean scientists who pioneer new fields of research in biological sciences. From 2017 to this year, SUHF has selected 20 promising scientists in the field of biological sciences. Selected scientists are provided with up to KRW 500 million each year for five years. The foundation has provided a total of KRW 48.5 billion in research funds to date.
2021.09.15
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3D Visualization and Quantification of Bioplastic PHA in a Living Bacterial Cell
3D holographic microscopy leads to in-depth analysis of bacterial cells accumulating the bacterial bioplastic, polyhydroxyalkanoate (PHA) A research team at KAIST has observed how bioplastic granule is being accumulated in living bacteria cells through 3D holographic microscopy. Their 3D imaging and quantitative analysis of the bioplastic ‘polyhydroxyalkanoate’ (PHA) via optical diffraction tomography provides insights into biosynthesizing sustainable substitutes for petroleum-based plastics. The bio-degradable polyester polyhydroxyalkanoate (PHA) is being touted as an eco-friendly bioplastic to replace existing synthetic plastics. While carrying similar properties to general-purpose plastics such as polyethylene and polypropylene, PHA can be used in various industrial applications such as container packaging and disposable products. PHA is synthesized by numerous bacteria as an energy and carbon storage material under unbalanced growth conditions in the presence of excess carbon sources. PHA exists in the form of insoluble granules in the cytoplasm. Previous studies on investigating in vivo PHA granules have been performed by using fluorescence microscopy, transmission electron microscopy (TEM), and electron cryotomography. These techniques have generally relied on the statistical analysis of multiple 2D snapshots of fixed cells or the short-time monitoring of the cells. For the TEM analysis, cells need to be fixed and sectioned, and thus the investigation of living cells was not possible. Fluorescence-based techniques require fluorescence labeling or dye staining. Thus, indirect imaging with the use of reporter proteins cannot show the native state of PHAs or cells, and invasive exogenous dyes can affect the physiology and viability of the cells. Therefore, it was difficult to fully understand the formation of PHA granules in cells due to the technical limitations, and thus several mechanism models based on the observations have been only proposed. The team of metabolic engineering researchers led by Distinguished Professor Sang Yup Lee and Physics Professor YongKeun Park, who established the startup Tomocube with his 3D holographic microscopy, reported the results of 3D quantitative label-free analysis of PHA granules in individual live bacterial cells by measuring the refractive index distributions using optical diffraction tomography. The formation and growth of PHA granules in the cells of Cupriavidus necator, the most-studied native PHA (specifically, poly(3-hydroxybutyrate), also known as PHB) producer, and recombinant Escherichia coli harboring C. necator PHB biosynthesis pathway were comparatively examined. From the reconstructed 3D refractive index distribution of the cells, the team succeeded in the 3D visualization and quantitative analysis of cells and intracellular PHA granules at a single-cell level. In particular, the team newly presented the concept of “in vivo PHA granule density.” Through the statistical analysis of hundreds of single cells accumulating PHA granules, the distinctive differences of density and localization of PHA granules in the two micro-organisms were found. Furthermore, the team identified the key protein that plays a major role in making the difference that enabled the characteristics of PHA granules in the recombinant E. coli to become similar to those of C. necator. The research team also presented 3D time-lapse movies showing the actual processes of PHA granule formation combined with cell growth and division. Movies showing the living cells synthesizing and accumulating PHA granules in their native state had never been reported before. Professor Lee said, “This study provides insights into the morphological and physical characteristics of in vivo PHA as well as the unique mechanisms of PHA granule formation that undergo the phase transition from soluble monomers into the insoluble polymer, followed by granule formation. Through this study, a deeper understanding of PHA granule formation within the bacterial cells is now possible, which has great significance in that a convergence study of biology and physics was achieved. This study will help develop various bioplastics production processes in the future.” This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (Grants NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) and the Bio & Medical Technology Development Program (Grant No. 2021M3A9I4022740) from the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea to S.Y.L. This work was also supported by the KAIST Cross-Generation Collaborative Laboratory project. -PublicationSo Young Choi, Jeonghun Oh, JaeHwang Jung, YongKeun Park, and Sang Yup Lee. Three-dimensional label-free visualization and quantification of polyhydroxyalkanoates in individualbacterial cell in its native state. PNAS(https://doi.org./10.1073/pnas.2103956118) -ProfileDistinguished Professor Sang Yup LeeMetabolic Engineering and Synthetic Biologyhttp://mbel.kaist.ac.kr/ Department of Chemical and Biomolecular Engineering KAIST Endowed Chair Professor YongKeun ParkBiomedical Optics Laboratoryhttps://bmokaist.wordpress.com/ Department of PhysicsKAIST
2021.07.28
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VP Sang Yup Lee Honored with the Pony Chung Innovation Award
Vice President for Research Sang Yup Lee became the recipient of the Innovation Award by the Pony Chung Foundation that was established to honor the late Se-yung Chung, the former chairman of Hyundai Development Company. He will receive 200 million KRW in prize money. Chairman Chung developed Korea’s first domestically manufactured automobile, ‘Pony,’ in the mid-1970s that became the cornerstone of Korea’s auto industry today. Distinguished Professor Lee, from the Department of Chemical and Biomolecular Engineering, is a pioneering scholar in the field of systems metabolic engineering who developed various micro-organisms for producing a wide range of fuels, chemicals, materials, and natural compounds. He recently was elected as a foreign member of the Royal Society in the UK and is the first Korean ever elected into the National Academy of Inventors (NAI) in the US as well as one of 13 scholars elected as an International Member of both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US.
2021.07.13
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Professor Jung Receives the Hansong Science Award
Professor Yousung Jung of the Department of Chemical and Biomolecular Engineering has been selected as the recipient of the 5th Hansong Science Award in Chemistry. The award recognizes young and mid-career scholars who made outstanding achievement in physics, chemistry, and life sciences. Recipients receive 50 million KRW in prize money. Professor Jung was recognized for finding a new way to predict synthesis potentials when designing data-based materials and molecules through AI-powered inverse technology. Conventionally, new material discovery mainly relied on a method where the new materials were proposed by an expert’s intuition or experimental trial, then synthesized to measure the properties of the material before it was used. However, this method took a lot of time, which resulted in an inefficient discovery process. Professor Jung’s AI reverse design technology is reported to be more efficient for discovering new materials by finding crystal structures with desired properties using data and AI algorithms. "AI reverse design technology can accelerate the development of new materials and new drugs," Professor Jung said. "It can be used as an algorithm for future autonomous laboratories implemented by robots, algorithms, and data without human intervention," he added.
2021.07.13
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Hydrogel-Based Flexible Brain-Machine Interface
The interface is easy to insert into the body when dry, but behaves ‘stealthily’ inside the brain when wet Professor Seongjun Park’s research team and collaborators revealed a newly developed hydrogel-based flexible brain-machine interface. To study the structure of the brain or to identify and treat neurological diseases, it is crucial to develop an interface that can stimulate the brain and detect its signals in real time. However, existing neural interfaces are mechanically and chemically different from real brain tissue. This causes foreign body response and forms an insulating layer (glial scar) around the interface, which shortens its lifespan. To solve this problem, the research team developed a ‘brain-mimicking interface’ by inserting a custom-made multifunctional fiber bundle into the hydrogel body. The device is composed not only of an optical fiber that controls specific nerve cells with light in order to perform optogenetic procedures, but it also has an electrode bundle to read brain signals and a microfluidic channel to deliver drugs to the brain. The interface is easy to insert into the body when dry, as hydrogels become solid. But once in the body, the hydrogel will quickly absorb body fluids and resemble the properties of its surrounding tissues, thereby minimizing foreign body response. The research team applied the device on animal models, and showed that it was possible to detect neural signals for up to six months, which is far beyond what had been previously recorded. It was also possible to conduct long-term optogenetic and behavioral experiments on freely moving mice with a significant reduction in foreign body responses such as glial and immunological activation compared to existing devices. “This research is significant in that it was the first to utilize a hydrogel as part of a multifunctional neural interface probe, which increased its lifespan dramatically,” said Professor Park. “With our discovery, we look forward to advancements in research on neurological disorders like Alzheimer’s or Parkinson’s disease that require long-term observation.” The research was published in Nature Communications on June 8, 2021. (Title: Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity) The study was conducted jointly with an MIT research team composed of Professor Polina Anikeeva, Professor Xuanhe Zhao, and Dr. Hyunwoo Yook. This research was supported by the National Research Foundation (NRF) grant for emerging research, Korea Medical Device Development Fund, KK-JRC Smart Project, KAIST Global Initiative Program, and Post-AI Project. -PublicationPark, S., Yuk, H., Zhao, R. et al. Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity. Nat Commun 12, 3435 (2021). https://doi.org/10.1038/s41467-021-23802-9 -ProfileProfessor Seongjun ParkBio and Neural Interfaces LaboratoryDepartment of Bio and Brain EngineeringKAIST
2021.07.13
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Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS). Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3. Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives. The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds. The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected. “We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST. “The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee. This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326). -PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118) -ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
2021.07.08
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Prof. Sang Wan Lee Selected for 2021 IBM Academic Award
Professor Sang Wan Lee from the Department of Bio and Brain Engineering was selected as the recipient of the 2021 IBM Global University Program Academic Award. The award recognizes individual faculty members whose emerging science and technology contains significant interest for universities and IBM. Professor Lee, whose research focuses on artificial intelligence and computational neuroscience, won the award for his research proposal titled A Neuroscience-Inspired Approach for Metacognitive Reinforcement Learning. IBM provides a gift of $40,000 to the recipient’s institution in recognition of the selection of the project but not as a contract for services. Professor Lee’s project aims to exploit the unique characteristics of human reinforcement learning. Specifically, he plans to examines the hypothesis that metacognition, a human’s ability to estimate their uncertainty level, serves to guide sample-efficient and near-optimal exploration, making it possible to achieve an optimal balance between model-based and model-free reinforcement learning. He was also selected as the winner of the Google Research Award in 2016 and has been working with DeepMind and University College London to conduct basic research on decision-making brain science to establish a theory on frontal lobe meta-enhance learning. "We plan to conduct joint research for utilizing brain-based artificial intelligence technology and frontal lobe meta-enhanced learning technology modeling in collaboration with an international research team including IBM, DeepMind, MIT, and Oxford,” Professor Lee said.
2021.06.25
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Natural Rainbow Colorants Microbially Produced
Integrated strategies of systems metabolic engineering and membrane engineering led to the production of natural rainbow colorants comprising seven natural colorants from bacteria for the first time A research group at KAIST has engineered bacterial strains capable of producing three carotenoids and four violacein derivatives, completing the seven colors in the rainbow spectrum. The research team integrated systems metabolic engineering and membrane engineering strategies for the production of seven natural rainbow colorants in engineered Escherichia coli strains. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries. Colorants are widely used in our lives and are directly related to human health when we eat food additives and wear cosmetics. However, most of these colorants are made from petroleum, causing unexpected side effects and health problems. Furthermore, they raise environmental concerns such as water pollution from dyeing fabric in the textiles industry. For these reasons, the demand for the production of natural colorants using microorganisms has increased, but could not be readily realized due to the high cost and low yield of the bioprocesses. These challenges inspired the metabolic engineers at KAIST including researchers Dr. Dongsoo Yang and Dr. Seon Young Park, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team reported the study entitled “Production of rainbow colorants by metabolically engineered Escherichia coli” in Advanced Science online on May 5. It was selected as the journal cover of the July 7 issue. This research reports for the first time the production of rainbow colorants comprising three carotenoids and four violacein derivatives from glucose or glycerol via systems metabolic engineering and membrane engineering. The research group focused on the production of hydrophobic natural colorants useful for lipophilic food and dyeing garments. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, three carotenoids comprising astaxanthin (red), -carotene (orange), and zeaxanthin (yellow), and four violacein derivatives comprising proviolacein (green), prodeoxyviolacein (blue), violacein (navy), and deoxyviolacein (purple) could be produced. Thus, the production of natural colorants covering the complete rainbow spectrum was achieved. When hydrophobic colorants are produced from microorganisms, the colorants are accumulated inside the cell. As the accumulation capacity is limited, the hydrophobic colorants could not be produced with concentrations higher than the limit. In this regard, the researchers engineered the cell morphology and generated inner-membrane vesicles (spherical membranous structures) to increase the intracellular capacity for accumulating the natural colorants. To further promote production, the researchers generated outer-membrane vesicles to secrete the natural colorants, thus succeeding in efficiently producing all of seven rainbow colorants. It was even more impressive that the production of natural green and navy colorants was achieved for the first time. “The production of the seven natural rainbow colorants that can replace the current petroleum-based synthetic colorants was achieved for the first time,” said Dr. Dongsoo Yang. He explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals. “As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Lee. This work was supported by the "Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01550602)" Rural Development Administration, Republic of Korea. -Publication:Dongsoo Yang, Seon Young Park, and Sang Yup Lee. Production of rainbow colorants by metabolically engineered Escherichia coli. Advanced Science, 2100743. -Profile Distinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
2021.06.09
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Ultrafast, on-Chip PCR Could Speed Up Diagnoses during Pandemics
A rapid point-of-care diagnostic plasmofluidic chip can deliver result in only 8 minutes Reverse transcription-polymerase chain reaction (RT-PCR) has been the gold standard for diagnosis during the COVID-19 pandemic. However, the PCR portion of the test requires bulky, expensive machines and takes about an hour to complete, making it difficult to quickly diagnose someone at a testing site. Now, researchers at KAIST have developed a plasmofluidic chip that can perform PCR in only about 8 minutes, which could speed up diagnoses during current and future pandemics. The rapid diagnosis of COVID-19 and other highly contagious viral diseases is important for timely medical care, quarantining and contact tracing. Currently, RT-PCR uses enzymes to reverse transcribe tiny amounts of viral RNA to DNA, and then amplifies the DNA so that it can be detected by a fluorescent probe. It is the most sensitive and reliable diagnostic method. But because the PCR portion of the test requires 30-40 cycles of heating and cooling in special machines, it takes about an hour to perform, and samples must typically be sent away to a lab, meaning that a patient usually has to wait a day or two to receive their diagnosis. Professor Ki-Hun Jeong at the Department of Bio and Brain Engineering and his colleagues wanted to develop a plasmofluidic PCR chip that could quickly heat and cool miniscule volumes of liquids, allowing accurate point-of-care diagnoses in a fraction of the time. The research was reported in ACS Nano on May 19. The researchers devised a postage stamp-sized polydimethylsiloxane chip with a microchamber array for the PCR reactions. When a drop of a sample is added to the chip, a vacuum pulls the liquid into the microchambers, which are positioned above glass nanopillars with gold nanoislands. Any microbubbles, which could interfere with the PCR reaction, diffuse out through an air-permeable wall. When a white LED is turned on beneath the chip, the gold nanoislands on the nanopillars quickly convert light to heat, and then rapidly cool when the light is switched off. The researchers tested the device on a piece of DNA containing a SARS-CoV-2 gene, accomplishing 40 heating and cooling cycles and fluorescence detection in only 5 minutes, with an additional 3 minutes for sample loading. The amplification efficiency was 91%, whereas a comparable conventional PCR process has an efficiency of 98%. With the reverse transcriptase step added prior to sample loading, the entire testing time with the new method could take 10-13 minutes, as opposed to about an hour for typical RT-PCR testing. The new device could provide many opportunities for rapid point-of-care diagnostics during a pandemic, the researchers say. -Publication Ultrafast and Real-Time Nanoplasmonic On-Chip Polymerase Chain Reaction for Rapid and Quantitative Molecular Diagnostics ACS Nano (https://doi.org/10.1021/acsnano.1c02154) -Professor Ki-Hun Jeong Biophotonics Laboratory https://biophotonics.kaist.ac.kr/ Department of Bio and Brain Engineeinrg KAIST
2021.06.08
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