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Recombinant E. Coli As a Biofactory for the Biosynthesis of Diverse Nanomaterials
(Distinguished Professor Lee and PhD candidate Choi)
A metabolic research group at KAIST and Chung-Ang University in Korea has developed a recombinant E. coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table. Among the elements, the team could biosynthesize 33 novel nanomaterials for the first time, advancing the forward design of nanomaterials through the biosynthesis of various single and multi-elements.
The study analyzed the nanomaterial biosynthesis conditions using a Pourbaix diagram to predict the producibility and crystallinity. Researchers studied a Pourbaix diagram to predict the stable chemical species of each element for nanomaterial biosynthesis at varying levels of reduction potential (Eh) and pH. Based on the Pourbaix diagram analyses, the initial pH of the reaction was changed from 6.5 to 7.5, resulting in the biosynthesis of various crystalline nanomaterials that were previously amorphous or not synthesized.
This strategy was extended to biosynthesize multi-element nanomaterials. Various single and multi-element nanomaterials biosynthesized in this research can potentially serve as new and novel nanomaterials for industrial applications such as catalysts, chemical sensors, biosensors, bioimaging, drug delivery, and cancer therapy.
A research group consisting of PhD candidate Yoojin Choi, Associate Professor Doh Chang Lee, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST and Associate Professor Tae Jung Park of the Department of Chemistry at Chung-Ang University reported the synthesis. This study, entitled “Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials,” was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on May 21.
A recent successful biosynthesis of nanomaterials under mild conditions without requiring physical and chemical treatments has triggered the exploration of the full biosynthesis capacity of a biological system for producing a diverse range of nanomaterials as well as for understanding biosynthesis mechanisms for crystalline versus amorphous nanomaterials.
There has been increased interest in synthesizing various nanomaterials that have not yet been synthesized for various applications including semiconducting materials, enhanced solar cells, biomedical materials, and many others. This research reports the construction of a recombinant E. coli strain that co-expresses metallothionein, a metal binding protein, and phytochelatin synthase that synthesizes the metal-binding peptide phytochelatin for the biosynthesis of various nanomaterials. Subsequently, an E. coli strain was engineered to produce a diverse range of nanomaterials, including those never biosynthesized before, by using 35 individual elements from the periodic table and also by combining multi-elements.
Distinguished Professor Lee said, “An environmentally-friendly and sustainable process is of much interest for producing nanomaterials by not only chemical and physical methods but biological synthesis. Moreover, there has been much attention paid to producing diverse and novel nanomaterials for new industrial applications. This is the first report to predict the biosynthesis of various nanomaterials, by far the largest number of various single- and multi-elements nanomaterials. The strategies used for nanomaterial biosynthesis in this research will be useful for further diversifying the portfolio of nanomaterials that can be manufactured.”
Figure: The biosynthesis of diverse nanomaterials using recombinant E. coli. This schematic diagram shows the overall conceptualization of the biosynthesis of various single and multi-element nanomaterials using recombinant E. coli under incubation with corresponding elemental precursors. The 35 elements that were tested to biosynthesize nanomaterials are shown in black circles on the periodic table.
2018.05.23 View 11492 -
Capillary Forces at Work for Lithium-Sulfur Batteries
Professor Do Kyung Kim from the KAIST Department of Materials Science and Engineering and his team succeeded in developing high-areal-capacity lithium sulfur batteries (Li-S batteries) by capturing polysulfide with carbon nanofibers. This research will provide new batteries to replace existing lithium rechargeable batteries, shifting the commercialization of related technologies ahead.
Electrical vehicles and large-scale energy storage systems necessitate the development of batteries with high energy density and cost effectiveness, and Li-S batteries are known to be one of the promising alternatives to the predominant lithium ion batteries.
With six times as much energy density, Li-S batteries theoretically thrust electric vehicle to twice the distance of lithium ion batteries. Therefore, they have been spotlighted as next-generation lithium rechargeable batteries because they can go up to 400km once charged.
However, several issues make it challenging to readily commercialize Li-S batteries. The low electrical conductivity of sulfur, volumetric expansion and contraction of the battery during charge and discharge, and permanent damage of the electrode caused by the dissolution of the lithium polysulfide into the electrolyte – known as the “shuttle effect” – are three of the biggest obstacles to commercial-grade Li-S batteries.
While there have been numerous attempts to curb, avoid, or alleviate these issues — such as the physical encapsulation of sulfur using various metal oxides or carbonaceous matrices — most of them entail utilizing zero-dimensional (0D) carbon materials. This encapsulation method has been somewhat effective in enhancing the electrical conductivity of sulfur while simultaneously tolerating some volumetric alterations and suppressing the shuttle effect. The downside of 0D carbon material-based encapsulation methods is their complicated synthetic processing and the limited mass loading of sulfur.
With this in mind, the team set out to employ one-dimensional (1D) carbon materials instead. Unlike the 0D case, 1D carbon materials render a large surface area and a long-range conduction path for electrons and lithium ions. Being 1D also solves the undesirable high-contact resistance problem frequently encountered by 0D carbon material-based encapsulation.
The key to developing the proposed material was to exploit the capillary force to decrease the energy associated with the dissolution of polysulfides. As such, carbon nanofibers (CNFs) were found to be suitable for high-areal-capacity lithium-sulfur batteries since capillary force acting between CNFs can take advantage of the high electrical conductivity with the suppressed dissolution of sulfides.
The research findings show that sulfur was successfully contained in between the CNFs by wetting due to the capillary force without the need for complicated synthetic processing, as in the 0D case. The research results indicate that the sulfur contained per unit area (mg/cm2) is five times greater for the newly implemented method, which then enabled the lithium-sulfur battery to achieve an areal capacity of 7 mAh/cm2, which amounts to as much as at most seven times that of conventional lithium ion batteries.
First author Jong Hyuk Yun stated that the unprecedented methods utilized in this study will help further and widen the progress of lithium batteries in general. Meanwhile, Professor Kim said, “This study brought us closer to commercial-grade high-capacity Li-S batteries, which are applicable for a wide variety of products, including electric vehicles, unmanned aerial vehicles (UAVs), and drones.”
This research, led by PhD candidate Yun, was published in the 18th issue of this year’s Nano Letters.
Figure 1. Electrochemical reaction leading to the containment of the sulfur within the carbon nanofiber and the corresponding specific capacity of the battery over a number of charge-discharge cycles
Figure 2. SEM images of the first discharged electrode containing lithium sulfide at the junction between the nanofibers, and the first charged electrode
Figure 3. carbon nanofiber effectively absorbing liquid based lithium polysulfide
2018.05.14 View 7955 -
New Material for Generating Energy-Efficient Spin Currents
(Professor Byong-Guk Park (left) and Professor Kab-Jin Kim)
Magnetic random access memory (MRAM) is emerging as next-generation memory. It allows information to be kept even without an external power supply and its unique blend of high density and high speed operation is driving global semiconductor manufacturers to develop new versions continuously.
A KAIST team, led by Professor Byong-Guk Park in the Department of Materials Science and Engineering and Professor Kab-Jin Kim in the Department of Physics, recently has developed a new material which enables the efficient generation of a spin current, the core part of operating MRAM. This new material consisting of ferromagnet-transition metal bilayers can randomly control the direction of the generated spin current unlike the existing ones.
They also described a mechanism for spin-current generation at the interface between the bottom ferromagnetic layer and the non-magnetic spacer layer, which gives torques on the top magnetic layer that are consistent with the measured magnetization dependence.
When applying this to spin-orbit torque magnetic memory, it shows the increased efficiency of spin torque and generation of the spin current without an external magnetic field. High-speed operation, the distinct feature of spin-orbit torque-based MRAM that carries its non-volatility, can significantly reduce the standby power better than SRAM.
This new material will expect to speed up the commercialization of MRAM. The research team said that this magnetic memory will further be applied to mobile, wearable, and IoT devices.
This study, conducted in collaboration with Professor Kyung-Jin Lee from Korea University and Dr. Mark Stiles from the National Institute of Standards and Technology in the US, was featured in Nature Materials in March. The research was funded by the Creative Materials Discovery Program of the Ministry of Science and ICT.
(Figure: Ferromagnet-transition metal bilayers which can randomly control the direction of the generated spin current)
2018.05.11 View 10162 -
The First Recipient of the KPS Award in Plasma Physics
( Research Professor Sanghoo Park)
Research Professor Sanghoo Park received the Young Researcher Award in Plasma Physics during the Korean Physical Society (KPS)’s Spring Meeting from April 25 to 27.
He is a KAIST graduate with a PhD in Physics and currently holds the position of research professor in the Department of Nuclear and Quantum Engineering.
The Young Researcher Award in Plasma Physics is given to a specialist in plasma who has the potential to make a contribution to plasma and accelerator physics in Korea.
Professor Park has gained recognition for his work, including awards, publications in 24 journals, and 12 technical patent registrations of plasma, which led to his selection as the recipient of this award.
He is now conducting a leading role in this field nationally and internationally by delving into the study of partially-ionized plasma.
Professor Park said, “It is my great honor to become the first recipient of the Young Researcher Award in Plasma Physics. I will continue to engage in research to develop the field of plasma in Korea.”
2018.05.08 View 6686 -
Professor Hee-Sung Park Named Scientist of May
(Professor Hee-Sung Park)
Professor Hee-Sung Park from the Department of Chemistry was named ‘Scientist of May’ sponsored by the Ministry of Science and ICT and the National Research Foundation of Korea. Professor Park was honored in recognition of his developing a tool to engineer designer proteins via diverse chemical modifications. This approach provides a novel platform for investigating numerous diseases such as cancer and dementia.
His research focuses on the production of synthetic proteins and the generation of diverse protein functions as well as the designing and engineering of new translation machinery for genetic code expansion, and the application of synthetic biology techniques for basic cell biology and applied medical science.
Post-translational modifications (PTMs) are constantly taking place during or after protein biosynthesis. PTMs play a vital role in expanding protein functional diversity and, as a result, critically affect numerous biological processes. Abnormal PTMs have been known to trigger various diseases including cancer and dementia. Therefore, this technology enables proteins to reproduce with specific modifications at selected residues and will significantly help establish experimental strategies to investigate fundamental biological mechanisms including the development of targeted cancer therapies.
Professor Park also received 10 million KRW in prize money.
2018.05.04 View 10030 -
Undergrad's Paper Chosen as the Cover Article in Soft Matter
(from left: Research Professor KyuHan Kim and Undergrad Student Subeen Kim)
A KAIST undergraduate student, Subeen Kim, had his paper chosen as the cover article in an international journal during his senior year.
There have been an increasing number of undergraduate students who were published as the first author because the KAIST Undergraduate Research Participation program allows more active research participation by undergraduate students.
Through URP, Kim successfully published his paper in the internationally-renowned journal, Soft Matter, which is published by the Royal Society of Chemistry, and it was chosen as the cover article of that journal in February 2018.
This publication means a lot to him because he designed the cover image himself, based on his imagination and observations.
His research is about controllable one-step double emulsion formation. Double emulsion is a system in which dispersed droplets contain additional immiscible liquid droplets.
Having great retention ability, double emulsion has been used in various applications in the food industry, in cosmetics, and for drug delivery. Nevertheless, two-step emulsification is a conventional approach to produce double emulsions that typically leads to partial destabilization of the emulsion formed during the initial stage. Hence, it does not ensure the stability of a double emulsion. On the other hand, a microfluidic approach with various flow-focusing techniques has been developed, but it has low production efficiency and thus limited industrial applications.
Kim’s results came from the process of phase inversion to solve this problem. He identified the instant formation of double emulsions during the process of phase inversion. Based on this finding, he proposed criteria to achieve high stability of double emulsion.
Through constant research, he developed a quite general method using a combination of an oil soluble poly methyl methacrylate (PMMA) and hydrophobic silica nanoparticle (HDK H18). This new method enables one-step and stable production of double emersions in a stable manner. It also allows control of the number and the volume of inner oil droplets inside the outer water droplets by adjusting PMMA and HDK H18.
Kim enrolled at KAIST as a KAIST Presidential Fellowship and Presidential Science Scholarship in 2014. While studying both chemical and biomolecular engineering and chemistry he has been developing his hypothesis and conducting research.
He was able to begin conducting research because he has taken part in URP projects twice. In his sophomore year, he studied the formation of high internal phase double emulsions. After one year, he conducted research to produce superabsorbent resins, which are the base material for diapers, by using colloid particles. Using partial research outcomes, he published his paper in Nature Communications as a second author.
Kim said, “Double majoring the chemical and biomolecular engineering and chemistry has helped me producing this outcome. I hope that this research contributes to commercializing double emulsions. I will continue to identify accurate principles to produce chemicals that can be controlled exquisitely.”
Figure 1. The cover article of Soft Matter
2018.05.03 View 10786 -
Cross-Generation Collaborative Labs Open
KAIST opened two cross-generation collaborative labs last month. This novel approach will pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires.
This is one of the Vision 2031 innovation initiatives established to extend the spectrum of knowledge and research competitiveness. The selected labs will be funded for five years and the funding will be extended if necessary. KAIST will continue to select new labs every year.
A five-member selection committee including the Nobel Laureates Professor Klaus Von Klitzing at the Max-Planck Institute for Solid State Research and Dr. Kurt Wüthrich from ETH Zürich selected the first two labs with senior-junior pairs in March.
(Two renowned scholars' Cross-Generation Collaborative Labs which opened last month.
Distinguished Professor Lee's lab (above) andChair Professor Sung's lab)
Both labs are run by world-renowned scholars: the Systems Metabolic Engineering and Systems Healthcare Laboratory headed by Distinguished Professor Sang-Yup Lee in the Department of Chemical and Biomolecular Engineering and the Acousto-Microfluidics Research Center for Next-Generation Healthcare led by Chair Professor Hyung Jin Sung in the Department of Mechanical Engineering.
Distinguished Professor Lee will be teamed up with Professor Hyun Uk Kim, and their lab aims to mass produce new eco-friendly chemical materials as well as higher-value-added materials which will be used for medicine. The new platform technologies created in the lab are expected to provide information which will benefit human healthcare.
Meanwhile, the Acousto-Microfluidics Research Center for Next-Generation Healthcare will team up with Professors Hyoungsoo Kim and Yeunwoo Cho under Chair Professor Sung. The lab will conduct research on controlling fluids and objects exquisitely on a micro-nano scale by using high-frequency acoustic waves. The lab plans to develop a next-generation healthcare platform for customized diagnoses as well as disease treatment.
KAIST President Sung-Chul Shin, who introduced this novel idea in his research innovation initiative, said that he hopes the Cross-Generation Collaborative Labs will contribute to honoring senior scholars’ research legacies and passing knowledge down to junior researchers in order to further develop their academic achievements. He said, “I sincerely hope the labs will make numerous research breakthroughs in the very near future.”
2018.05.03 View 11760 -
Professor Ju, to Receive Grants from HFSP
(Professor Young Seok Ju)
Professor Young Seok Ju from the Graduate School of Medical Science and Engineering was selected as a young investigator to receive research funds from the Human Frontiers Science Program.
The Human Frontiers Science Program (HFSP) was founded in 1989 with members of the G7 and European Union to stimulate innovative research in the field of life sciences.
Professor Ju placed third out of the eight teams that were selected from 158 applicants representing 60 countries. He is now the fourth Korean to receive a research grant as a young investigator. Professor Jae Kyoung Kim from the Department of Mathematical Sciences also received this prize last year, hence KAIST has produced grant recipients for two consecutive years.
Professor Ju is a medical doctor specializing in cancer genomics and computer biology. He has been studying somatic mutations and their functional consequences in human cancer in a bioinformatics way. He has published papers in international journals including Nature, Science, Genome Research, and Journal of Clinical Oncology.
With a title ‘Tracing AID/APOBEC- and MSI-mediated hyper-mutagenesis in the clonal evolution of gastric cancer,’ Professor Ju will receive 1.05 million dollars for three years along with Professor Bon-Kyoung Koo from the Institute of Molecular Biotechnology at Austrian Academy of Sciences, and Sinppert Hugo from University Medical Center Utrecht.
Professor Ju said, “As a young investigator, it is my great honor to receive this research fund from this organization. Through this internationally collaborative research, I will carry out groundbreaking research to understand the pathophysiology of cancers at a molecular level.”
2018.04.24 View 8670 -
Deep Learning Predicts Drug-Drug and Drug-Food Interactions
A Korean research team from KAIST developed a computational framework, DeepDDI, that accurately predicts and generates 86 types of drug-drug and drug-food interactions as outputs of human-readable sentences, which allows in-depth understanding of the drug-drug and drug-food interactions.
Drug interactions, including drug-drug interactions (DDIs) and drug-food constituent interactions (DFIs), can trigger unexpected pharmacological effects, including adverse drug events (ADEs), with causal mechanisms often unknown. However, current prediction methods do not provide sufficient details beyond the chance of DDI occurrence, or require detailed drug information often unavailable for DDI prediction.
To tackle this problem, Dr. Jae Yong Ryu, Assistant Professor Hyun Uk Kim and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at Korea Advanced Institute of Science and Technology (KAIST), developed a computational framework, named DeepDDI, that accurately predicts 86 DDI types for a given drug pair. The research results were published online in Proceedings of the National Academy of Sciences of the United States of America (PNAS) on April 16, 2018, which is entitled “Deep learning improves prediction of drug-drug and drug-food interactions.”
DeepDDI takes structural information and names of two drugs in pair as inputs, and predicts relevant DDI types for the input drug pair. DeepDDI uses deep neural network to predict 86 DDI types with a mean accuracy of 92.4% using the DrugBank gold standard DDI dataset covering 192,284 DDIs contributed by 191,878 drug pairs. Very importantly, DDI types predicted by DeepDDI are generated in the form of human-readable sentences as outputs, which describe changes in pharmacological effects and/or the risk of ADEs as a result of the interaction between two drugs in pair. For example, DeepDDI output sentences describing potential interactions between oxycodone (opioid pain medication) and atazanavir (antiretroviral medication) were generated as follows: “The metabolism of Oxycodone can be decreased when combined with Atazanavir”; and “The risk or severity of adverse effects can be increased when Oxycodone is combined with Atazanavir”. By doing this, DeepDDI can provide more specific information on drug interactions beyond the occurrence chance of DDIs or ADEs typically reported to date.
DeepDDI was first used to predict DDI types of 2,329,561 drug pairs from all possible combinations of 2,159 approved drugs, from which DDI types of 487,632 drug pairs were newly predicted. Also, DeepDDI can be used to suggest which drug or food to avoid during medication in order to minimize the chance of adverse drug events or optimize the drug efficacy. To this end, DeepDDI was used to suggest potential causal mechanisms for the reported ADEs of 9,284 drug pairs, and also predict alternative drug candidates for 62,707 drug pairs having negative health effects to keep only the beneficial effects. Furthermore, DeepDDI was applied to 3,288,157 drug-food constituent pairs (2,159 approved drugs and 1,523 well-characterized food constituents) to predict DFIs. The effects of 256 food constituents on pharmacological effects of interacting drugs and bioactivities of 149 food constituents were also finally predicted. All these prediction results can be useful if an individual is taking medications for a specific (chronic) disease such as hypertension or diabetes mellitus type 2.
Distinguished Professor Sang Yup Lee said, “We have developed a platform technology DeepDDI that will allow precision medicine in the era of Fourth Industrial Revolution. DeepDDI can serve to provide important information on drug prescription and dietary suggestions while taking certain drugs to maximize health benefits and ultimately help maintain a healthy life in this aging society.”
Figure 1. Overall scheme of Deep DDDI and prediction of food constituents that reduce the in vivo concentration of approved drugs
2018.04.18 View 11844 -
Professor Gou Young Koh, 2018 Laureate of Ho-Am Prize
Distinguished Professor Gou Young Koh from the Graduate School of Medical Science and Engineering was appointed a 2018 laureate in medicine of the Ho-Am Prize by the Ho-Am Foundation. Professor Koh is a renowned expert in the field of tumor angiogenesis by exploring the hidden nature of capillary and lymphatic vessels in human organs.
He was recognized for demonstrating the effective reduction of tumor progression and metastasis via tumor vessel normalization. This counterintuitive study result is regarded as a stepping stone for a drug discovery to prevent microvascular diseases.
Besides Professor Koh, Professor Hee Oh from Yale University (Science), Professor Nam-Gyu Park from Sungkyunkwan University (Engineering), Opera Singer Kwangchul Youn (The Arts) and Sister Carla Kang (Community Service) received awards.
The Ho-Am Prize is presented to individuals who have contributed to academics, the arts, and social development, or furthered the welfare of humanity, and commemorates the noble spirit of public service espoused by the late Chairman Byung-chull Lee, who used the pen name Ho-Am.
It was established in 1990 by Kun-Hee Lee, the chairman of Samsung. Awards have been presented to 143 individuals worth a total of 24.4 billion KRW.
2018.04.11 View 8421 -
KAIST to Host FinTech Conference 2018
KAIST will be hosting a FinTech Conference with Princeton University (USA), Tsinghua University (China), and EDHEC Business School (France) in Seoul from April 12 to 13 titled State of the Art in Robo-Advising Systems: Financial Technologies for Enhanced Social Security.
The Bendhein Center for Finance and Department of Operations Research and Financial Engineering from Princeton University, Fintech Lab from Tsinghua University, and the Risk Institute from EDHEC will participate as co-hosting organizations in this conference organized by the Department of Industrial & Systems Engineering and the KAIST Center for Wealth Management Technologies.
The conference will discuss issues required for providing customized asset management to the public in terms of theory, technology, and industry.
During the conference, KAIST President Sung-Chul Shin and Chairman and CEO of the National Pension Service Sung Joo Kim will deliver welcoming addresses.
Professor John Mulvey from Princeton University, Professor Michael Dempster from Cambridge University, Professors Wei Xu and Changle Lin from Tsinghua University, Professor Lionel Martellini from EDHEC, and Professor Woo Chang Kim from KAIST are some of the invited speakers at the event.
Moreover, renowned experts in related fields will also participate in the conference, including Founder of Vanguard Group John Bogle, Jin Lee from Ant Financial, Youngsuh Cho from Shinhan Financial Group, Jung-Hwan Lee from Samsung Asset Management, and Hye Young Sung from the National Pension Service Research Institute.
Professor Kim said, “Only a small number of wealthy people can receive life-cycle customized asset management services due to the high cost structure; however, new technology derived from the Fourth Industrial Revolution can reduce the service price in an innovative manner, ultimately leading it to be popularized.”
“In an era with the poverty rate of older people reaching almost 50%.Fintech can enable individuals to manage their assets in an active manner, reinforcing social security without additional social costs in the period,” he added.
These four universities have been hosting the FinTech Conference since 2017. China will host the conference this fall, followed by France next year.
Samsung Asset Management, Alibaba Group, and Ant Financial will sponsor the conference. Anyone interested in this event can find more details at http://wmt.kaist.ac.kr/conference.html.
2018.04.02 View 8289 -
Two Professors Receive the Asan Medical Award
(Professor Ho Min Kim and Chair Profesor Eunjoon Kim (from far right)
Chair Professor Eunjoon Kim of the Department of Biological Sciences and Professor Ho Min Kim from the Graduate School of Medical Science & Engineering won the 11th Asan Medical Award in the areas of basic medicine and young medical scholar on March 21.
The Asan Medical Award has been recognizing the most distinguished scholars in the areas of basic and clinical medicines annually since 2007.
Chair Professor Kim won the 300 million KRW award in recognition of his research in the mechanism of synaptic brain dysfunction and its relation with neural diseases.
The young medical scholar’s award recognizes a promising scholar under the age of 40. Professor Kim won the award for identifying the key protein structure and molecular mechanism controlling immunocytes and neurons. He earned a 50 million KRW prize.
2018.03.26 View 9127