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Technology to Find Optimum Drug Target for Cancer Developed
(Professor Kwang-Hyun Cho (right) and lead author Dr. Minsoo Choi) A KAIST research team led by Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering developed technology to find the optimum drug target according to the type of cancer cell. The team used systems biology to analyze molecular network dynamics that reflect genetic mutations in cancer cells and to predict drug response. The technology could contribute greatly to future anti-cancer drug development. There are many types of genetic variations found in cancer cells, including gene mutations and copy number variations. These variations differ in cancer cells even within the same type of cancer, and thus the drug response varies cell by cell. Cancer researchers worked towards identifying frequently occurring genetic variations in cancer patients and, in particular, the mutations that can be used as an index for specific drugs. Previous studies focused on identifying a single genetic mutation or creating an analysis of the structural characteristics of a gene network. However, this approach was limited in its inability to explain the biological properties of cancer which are induced by various gene and protein interactions in cancer cells, which result in differences in drug response. Gene mutations in cancer cells not only affect the function of the affected gene, but also other genes that interact with the mutated gene and proteins. As a consequence, one mutation could lead to changes in the dynamical properties of the molecular network. Therefore, the responses to anti-cancer drugs by cancer cells differ. The current treatment approach that ignores molecular network dynamics and targets a few cancer-related genes is only effective on a fraction of patients, while many other patients exhibit resistance to the drug. Professor Cho’s team integrated a large-scale computer simulation using super-computing and cellular experiments to analyze changes in molecular network dynamics in cancer cells. This led to development of technology to find the optimum drug target according to the type of cancer cells by predicting drug response. This technology was applied to the molecular network of known tumor suppressor p53. The team used large-scale cancer cell genomic data available from The Cancer Cell Line Encyclopedia (CCLE) to construct different molecular networks specific to the characteristics of genetic variations. Perturbation analysis on drug response in each molecular network was used to quantify changes in cancer cells from drug response and similar networks were clustered. Then, computer simulations were used to analyze the synergetic effects in terms of efficacy and combination to predict the level of drug response. Based on the simulation results from various cancer cell lines including lung, breast, bone, skin, kidney, and ovary cancers were used in drug response experiments for compare analysis. This technique can be applied in any molecular network to identify the optimum drug target for personalized medicine. The research team suggests that the technology can analyze varying drug response due to the heterogeneity of cancer cells by considering the overall modulatory interactions rather than focusing only on a specific gene or protein. Further, the technology aids the prediction of causes of drug resistance and thus the identification of the optimum drug target to inhibit the resistance. This could be core source technology that can be used in drug repositioning, a process of applying existing drugs to new disease targets. Professor Cho said, “Genetic variations in cancer cells are the cause of diverse drug response, but a complete analysis had not yet been made.” He continued, “Systems biology allowed the simulation of drug responses by cancer cell molecular networks to identify fundamental principles of drug response and optimum drug targets using a new conceptual approach.” This research was published in Nature Communications on December 5 and was funded by Ministry of Science and ICT and National Research Foundation of Korea. (Figure 1. Drug response prediction for each cancer cell type from computer simulation and cellular experiment verification for comparison) (Figure 2. Drug response prediction based on cancer cell molecular network dynamics and clustering of cancer cells by their molecular networks) (Figure 3. Identification of drug target for each cancer cell type by cellular molecular network analysis and establishment for personalized medicine strategy for each cancer patient)
A New Spin Current Generating Material Developed
(Professor Park(left) and Ph.D. candidate Kim) Magnetic random-access memory (MRAM) is a non-volatile device made of thin magnetic film that can maintain information without an external power supply, in contrast to conventional silicon-based semiconductor memory. It also has the potential for high-density integration and high-speed operation. The operation of MRAM involves the control of the magnetization direction by exerting spin current-induced torque on a magnetic material. Spin current is generated using electricity in conventional MRAM, but this study developed materials technology that generates spin current using heat. A KAIST research team led by Professor Byong-Guk Park of the Department of Materials Science and Engineering developed a material that generates spin current from heat, which can be utilized for a new operation principle for MRAM. There have been theoretical reports on the spin Nernst effect, the phenomenon of the thermal generation of spin current, but is yet to have been experimentally proven due to technological limitations. However, the research team introduced a spin Nernst magnetoresistance measurement method using tungsten (W) and platinum (Pt) with high spin orbit coupling which allows for the experimental identification of the spin Nernst effect. They also demonstrated that the efficiency of spin current generation from heat is similar to that of spin current generated from electricity. Professor Park said, “This research has great significance in experimentally proving spin current generation from heat, a new physical phenomenon. We aim to develop the technology as a new operational method for MRAM through further research. This can lower power consumption, and is expected to contribute to the advancement of electronics requiring low power requirement such as wearable, mobile, and IOT devices”. This research was conducted as a joint research project with Professor Kyung-Jin Lee at Korea University and Professor Jong-Ryul Jeong at Chungnam National University. It was published in Nature Communications online on November 9 titled “Observation of transverse spin Nernst magnetoresistance induced by thermal spin current in ferromagnet/non-magnet bilayers.” Ph.D. candidate Dong-Jun Kim at KAIST is the first author. This research was funded by the Ministry of Science and ICT. (Schematic diagram of spin Nernst magnetoresistance) (Research result of new spin current generating materials)
Expanding Gas Storage Capacity of Nanoporous Materials
A KAIST research team led by Professor Jihan Kim of the Department of Chemical and Biomolecular Engineering has successfully proposed a rational defect engineering methodology that can greatly enhance the gas storage capacity of nanoporous materials. The team conducted a high-throughput computational screening of a large experimental metal-organic framework database to identify 13 candidate materials that could experience significant methane uptake enhancement with only a small proportion of linker vacancy defects. This research was published online on November 16 in Nature Communications, with M.S. candidate Sanggyu Chong from KAIST as the first author and post-doctorate researcher Günther Thiele from the Department of Chemistry at UC Berkeley as a contributing author. Metal-organic frameworks, hereinafter MOF, are crystalline nanoporous materials that are comprised of metal clusters and organic linkers continuously bound together by coordination bonds. Due to their ultrahigh surface areas and pore volumes, they have been widely studied for various energy and environment applications. Similar to other crystalline materials, MOFs are never perfectly crystalline and are likely to contain several different types of defects within their crystalline structures. Among these defects, linker vacancy defects, or the random absence of linker vacancies in their designated bonding positions, are known to be controllable by practicing careful control over the synthesis conditions. The research team combined the concepts of rational defect engineering over the linker vacancy defects and the potential presence of inaccessible pores within MOFs to propose a methodology where controlled the introduction of linker vacancy defects could lead to a dramatic enhancement in gas adsorption and storage capacities. The study utilized a Graphic Processing Unit (GPU) code developed by Professor Kim in a high-throughput computational screening of 12,000 experimentally synthesized MOFs to identify the structures with significant amounts of pores that were inaccessible for methane. In determining the presence of inaccessible pores, a flood-fill algorithm was performed over the energy-low regions of the structure, which is the same algorithm used for filling an area with color in Microsoft Paint. For the MOFs with significant amounts of inaccessible pores, as determined from the screening, the research team emulated linker vacancy defects in their crystalline structures so that the previously inaccessible pores would be newly merged into the main adsorption channel with the introduction of defects for additional surface area and pore volume available for adsorption. The research team successfully identified 13 structures that would experience up to a 55.56% increase in their methane uptake with less than 8.33% of the linker vacancy defects. The research team believes that this rational defect engineering scheme can be further utilized for many other applications in areas such as selective adsorption of an adsorbate from a gas mixture and the semi-permanent capture of gas molecules. This research was conducted with the support of the Mid-career Research Program of the National Research Foundation of Korea. Figure1. A diagram for flood fill algorithm and example of identification of inaccessible regions within the MOFs, using the flood fill algorithm Figure2. Methane energy contours before and after detect introduction
New Photocatalyst Converts Carbon Dioxide to 99% Pure Fuel
(Professor Song, Ph.D. candidates Kim, and Lim (from left)) A KAIST research team led by Professor Hyunjoon Song of the Department of Chemistry developed a metal oxide nanocatalyst that converts carbon dioxide to 99% pure methane. This technology directly uses sunlight to convert carbon dioxide into methane, which is more efficient in terms of energy storage capacity, compared to the conventional way of storing the electricity produced by solar cells in batteries. The research team used cheap catalytic materials to significantly enhance the reaction efficiency and selectivity of the chemical energy storage method. This research was conducted as a joint research project with Professor Ki Min Nam at Mokpo National University with co-first authors Dr. Kyung-Lyul Bae and Ph.D. candidates Jinmo Kim and Chan Kyu Lim. The study was published in Nature Communications on November 7. Although there is growing interest in sunlight as an energy resource, its usage has been limited to daytime and the power output varies with the weather. If sunlight could be directly converted to chemical energy, such as fuel, the limitations of energy storage and its usage could be overcome. In particular, the usage of sunlight to convert carbon dioxide, a main cause of the greenhouse effect in our atmosphere, is of great interest since both energy and environmental issues can be addressed. However, the stability of carbon dioxide made it difficult to convert it to other molecules. Thus, there was a need for a catalyst with enhanced efficiency and selectivity. Professor Song’s team synthesized zinc oxide nanoparticles, often used in sun cream. The nanoparticles were then bound to copper oxide as single particles, forming a colloidal form of zinc oxide-copper oxide nanoparticles. Zinc oxides produce high energy electrons using light, and this energy is used to convert carbon dioxide into methane. Further, zinc oxide can also produce electrons with light and transfer the electrons to copper oxide. Similar to the principles of photosynthesis in leaves, the electron transfer reaction could be maintained for a long time. As a consequence, although the reaction was conducted in aqueous solution, methane of 99% purity could be obtained from carbon dioxide. Conventional heterogeneous photocatalysts were in solid powder form with irregular structures and were not dispersed in water. Professor Song’s team used a nanochemical synthesis method to control the structure of the catalyst particles to be regular and maintained over a large surface area. This led to increasing carbon dioxide conversion activity by hundreds of fold in solution compared to existing catalysts. Professor Song said, “A long time will be needed for the commercialization of the direct conversion reaction of carbon dioxide using sunlight. However, the precise control of catalyst structures at nanoscale would enhance the efficiency of photocatalyst reactions.” He continued, “Applying this method to various phtocatalysts will maximize the catalysts performance.” (Figure 1. Scheme for carbon dioxide conversion reaction using nano photocatalyst in aqueous solution) (Figure 2. Structure, photocatalytic CO2 conversion, and stability of ZnO-Cu2O nanocatalyst )
Mutant Gene Network in Colon Cancer Identified
The principles of the gene network for colon tumorigenesis have been identified by a KAIST research team. The principles will be used to find the molecular target for effective anti-cancer drugs in the future. Further, this research gained attention for using a systems biology approach, which is an integrated research area of IT and BT. The KAIST research team led by Professor Kwang-Hyun Cho for the Department of Bio and Brain Engineering succeeded in the identification. Conducted by Dr. Dongkwan Shin and student researchers Jonghoon Lee and Jeong-Ryeol Gong, the research was published in Nature Communications online on November 2. Human cancer is caused by genetic mutations. The frequency of the mutations differs by the type of cancer; for example, only around 10 mutations are found in leukemia and childhood cancer, but an average of 50 mutations are found in adult solid cancers and even hundreds of mutations are found in cancers due to external factors, such as with lung cancer. Cancer researchers around the world are working to identify frequently found genetic mutations in patients, and in turn identify important cancer-inducing genes (called ‘driver genes’) to develop targets for anti-cancer drugs. However, gene mutations not only affect their own functions but also affect other genes through interactions. Therefore, there are limitations in current treatments targeting a few cancer-inducing genes without further knowledge on gene networks, hence current drugs are only effective in a few patients and often induce drug resistance. Professor Cho’s team used large-scale genomic data from cancer patients to construct a mathematical model on the cooperative effects of multiple genetic mutations found in gene interaction networks. The basis of the model construction was The Cancer Genome Atlas (TCGA) presented at the International Cancer Genome Consortium. The team successfully quantified the effects of mutations in gene networks to group colon cancer patients by clinical characteristics. Further, the critical transition phenomenon that occurs in tumorigenesis was identified using large-scale computer simulation analysis, which was the first hidden gene network principle to be identified. Critical transition is the phenomenon in which the state of matter is suddenly changed through phase transition. It was not possible to identify the presence of transition phenomenon in the past, as it was difficult to track the sequence of gene mutations during tumorigenesis. The research team used a systems biology-based research method to find that colon cancer tumorigenesis shows a critical transition phenomenon if the known driver gene mutations follow sequentially. Using the developed mathematical model, it can be possible to develop a new anti-cancer targeting drug that most effectively inhibits the effects of many gene mutations found in cancer patients. In particular, not only driver genes, but also other passenger genes affected by the gene mutations, could be evaluated to find the most effective drug targets. Professor Cho said, “Little was known about the contribution of many gene mutations during tumorigenesis.” He continued, “In this research, a systems biology approach identified the principle of gene networks for the first time to suggest the possibility of anti-cancer drug target identification from a new perspective.” This research was funded by the Ministry of Science and ICT and the National Research Foundation of Korea. Figure1. Formation of giant clusters via mutation propagation Figure2. Critical transition phenomenon by cooperative effect of mutations in tumorigenesis
Highly Flexible Organic Flash Memory for Foldable and Disposable Electronics
A KAIST team reported ultra-flexible organic flash memory that is bendable down to a radius of 300μm. The memory exhibits a significantly-long projected retention rate with a programming voltage on par with the present industrial standards. A joint research team led by Professor Seunghyup Yoo of the School of Electrical Engineering and Professor Sung Gap Im of the Department of Chemical and Biomolecular Engineering said that their memory technology can be applied to non-conventional substrates, such as plastics and papers, to demonstrate its feasibility over a wide range of applications. With Dr. Seungwon Lee and Dr. Hanul Moon playing the role of leading authors, the research was published in Nature Communications on September 28. Flash memory is a non-volatile, transistor-based data-storage device that has become essential in most electronic systems in daily life. With straightforward operation mechanisms and easy integration into NAND or NOR array architecture, flash memory has been established as the most successful and dominant non-volatile memory technology by far. Despite promising demonstrations in the early stages of organic electronics, the overall progress in this field has been far slower than that of thin-film transistors (TFTs) or other devices based on flexible materials. It has been challenging, in particular, to develop flash memory that simultaneously exhibits a significant level of flexibility and performance. This is mainly due to the scarcity of flexible dielectric layers, which are responsible for the tunneling and blocking of charges. The solution processing used for the preparation of most of the polymeric dielectric layers also makes it difficult to use them in flash memory due to the complexity involved in the formation of the bilayer dielectric structure, which is the key to flash memory operations. The research team tried to overcome these hurdles and realize highly flexible flash memory by employing thin polymeric insulators grown with initiated chemical vapor deposition (iCVD), a vapor-phase growth technique for polymers that was previously shown to be promising for the fabrication of flexible TFTs. It was further shown that these iCVD-based polymeric insulators, when coupled with rational device design and material choice, can make a significant contribution to flash memory as well. Memory using conventional polymer insulating films has often required a voltage as high as 100 V (volt) in order to attain long memory retention. If the device is made to operate at a low voltage, the short retention period of less than a month was problematic. The KAIST team produced flash memory with programming voltages around 10 V and a projected data retention time of over 10 years, while maintaining its memory performance even at a mechanical strain of 2.8%. This is a significant improvement over the existing inorganic insulation layer-based flash memory that allowed only a 1% strain. The team demonstrated the virtually foldable memory devices by fabricating the proposed flash memory on a 6-micrometer-thick ultrathin plastic film. In addition, it succeeded in producing them on printing paper, opening a way for disposable smart electronic products such as electronic paper and electronic business card. Professor Yoo said, " This study well illustrates that even highly flexible flash memory can be made to have a practically viable level of performance, so that it contributes to full-fledged wearable electronic devices and smart electronic paper." (Figure 1. Structure of flexible flash memory ) (Figure 2. Foldable flash memory)
High-Speed Motion Core Technology for Magnetic Memory
(Professor Kab-Jin Kim of the Department of Physics) A joint research team led by Professor Kab-Jin Kim of the Department of Physics, KAIST and Professor Kyung-Jin Lee at Korea University developed technology to dramatically enhance the speed of next generation domain wall-based magnetic memory. This research was published online in Nature Materials on September 25. Currently-used memory materials, D-RAM and S-RAM, are fast but volatile, leading to memory loss when the power is switched off. Flash memory is non-volatile but slow, while hard disk drives (HDD) have greater storage but are high in energy usage and weak in physical shock tolerance. To overcome the limitations of existing memory materials, ‘domain wall-based, magnetic memory’ is being researched. The core mechanism of domain wall magnetic memory is the movement of a domain wall by the current. Non-volatility is secured by using magnetic nanowires and the lack of mechanical rotation reduced power usage. This is a new form of high density, low power next-generation memory. However, previous studies showed the speed limit of domain wall memory to be hundreds m/s at maximum due to the ‘Walker breakdown phenomenon’, which refers to velocity breakdown from the angular precession of a domain wall. Therefore, there was a need to develop core technology to remove the Walker breakdown phenomenon and increase the speed for the commercialization of domain wall memory. Most domain wall memory studies used ferromagnetic bodies, which cannot overcome the Walker breakdown phenomenon. The team discovered that the use of ‘ferrimagnetic‘ GdFeCo at certain conditions could overcome the Walker breakdown phenomenon and using this mechanism they could increase domain wall speed to over 2Km/s at room temperature. Domain wall memory is high-density, low-power, and non-volatile memory. The memory could be the leading next-generation memory with the addition of the high speed property discovered in this research. Professor Kim said, “This research is significant in discovering a new physical phenomenon at the point at which the angular momentum of a ferrimagnetic body is 0 and it is expected to advance the implementation of next-generation memory in the future.” This research was funded by the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) (No. 2017R1C1B2009686, NRF-2016R1A5A1008184) and by the DGIST R&D Program of the Ministry of Science, ICT and Future Planning (17-BT-02). (Figure 1. Concept Map of Domain Wall Memory Material using Ferrimagnetic Body) (Figure 2. Scheme and Experimental Results of Domain Wall Speed Measurements)
The Medici Effect: Highly Flexible, Wearable Displays Born in KAIST
(Ph.D. candidate Seungyeop Choi) How do you feel when technology you saw in a movie is made into reality? Collaboration between the electrical engineering and textile industries has made TVs or smartphone screens displaying on clothing a reality. A research team led by Professor Kyung Cheol Choi at the School of Electrical Engineering presented wearable displays for various applications including fashion, IT, and healthcare. Integrating OLED (organic light-emitting diode) into fabrics, the team developed the most highly flexible and reliable technology for wearable displays in the world. Recently, information displays have become increasingly important as they construct the external part of smart devices for the next generation. As world trends are focusing on the Internet of Things (IoTs) and wearable technology, the team drew a lot of attention by making great progress towards commercializing clothing-shaped ‘wearable displays’. The research for realizing displays on clothing gained considerable attention from academia as well as industry when research on luminescence formed in fabrics was introduced in 2011; however, there was no technology for commercializing it due to its surface roughness and flexibility. Because of this technical limitation, clothing-shaped wearable displays were thought to be unreachable technology. However, the KAIST team recently succeeded in developing the world’s most highly efficient, light-emitting clothes that can be commercialized. The research team used two different approaches, fabric-type and fiber-type, in order to realize clothing-shaped wearable displays. In 2015, the team successfully laminated a thin planarization sheet thermally onto fabric to form a surface that is compatible with the OLEDs approximately 200 hundred nanometers thick. Also, the team reported their research outcomes on enhancing the reliability of operating fiber-based OLEDs. In 2016, the team introduced a dip-coating method, capable of uniformly depositing layers, to develop polymer light-emitting diodes, which show high luminance even on thin fabric. Based on the research performance in 2015 and 2016, Ph.D. candidate Seungyeop Choi took the lead in the research team and succeeded in realizing fabric-based OLEDs, showing high luminance and efficiency while maintaining the flexibility of the fabric. The long-term reliability of this wearable device that has the world’s best electrical and optical characteristics was verified through their self-developed, organic and inorganic encapsulation technology. According to the team, their wearable device facilitates the operation of OLEDs even at a bending radius of 2mm. According to Choi, “Having wavy structures and empty spaces, fiber plays a significant role in lowering the mechanical stress on the OLEDs.” “Screen displayed on our daily clothing is no longer a future technology,” said Professor Choi. “Light-emitting clothes will have considerable influence on not only the e-textile industry but also the automobile and healthcare industries.” Moreover, the research team remarked, “It means a lot to realize clothing-shaped OLEDs that have the world’s best luminance and efficiency. It is the most flexible fabric-based light-emitting device among those reported. Moreover, noting that this research carried out an in-depth analysis of the mechanical characteristics of the clothing-spared, light-emitting device, the research performance will become a guideline for developing the fabric-based electronics industry.” This research was funded by the Ministry of Trade, Industry and Energy and collaborated with KOLON Glotech, INC. The research performance was published in Scientific Reports in July. (OLEDs operating in fabrics) (Current-voltage-luminance and efficiency of the highly flexible, fabric-based OLEDs;Image of OLEDs after repetitive bending tests;Verification of flexibility through mechanical simulation)
Solutal Marangoni Flows of Miscible Liquid Drive Transport without Surface Contamination
(Professor Hyoungsoo Kim, Department of Mechanical Engineering, KAIST) A research team led by Hyoungsoo Kim, a professor of Mechanical Engineering at KAIST, succeeded in quantifying the phenomenon called, the Marangoni effect, which occurs at the interface between alcohol and water. It is expected that this finding will be a valuable resource used for effectively removing impurities from a surface fluid without any contamination, and developing materials that can replace surfactants. This research, co-conducted with a research team led by Professor Howard A. Stone at Princeton University, was published online in Nature Physics on July 31. The Marangoni effect, also known as tears of wine, is generated when two fluids having a different surface tension meet, causing finite mixing, spreading time and length scale. Typically, people believe that infinitely miscible liquids immediately mix together; however, it is not always true according to this paper. The typical surface tension of alcohol is three times lower than that of water, and this different surface tension generates the Marangoni-driven convection flow at the interface of the two liquids. In addition, there is a certain amount of time required for them to mix. This phenomenon has been discussed many times since it was discovered in early the 20th century, yet there was a limit to quantifying and explaining it. Professor Kim, considering the mixing and spreading mechanism, used various flow visualization techniques and equipment for capturing high speed images in his experiment. Through the flow visualization methods, the team succeeded in quantifying and explaining the complex, physicochemical phenomenon generated between water and alcohol. Moreover, they developed a theoretical model to predict the physicochemical hydrodynamic phenomena. The theoretical model can predict the speed of Marangoni-driven convection flow, the area of a drop of alcohol and the time required to develop the flow field. Hence, this model can map out types of materials (e.g., alcohol) and the volume of a drop of liquid as applicable to target a specific situation. Moreover, the research team believes that the interfacial flow enables the driving of bulk flows and that it can be a source of technology for effectively delivering drugs and removing impurities from a surface of substance without causing secondary contamination. Above all, the results show a possibility for replacing surfactant with alcohol as a material used for delivering drugs. In the case of the drug delivery, some drugs are encapsulated with a surfactant in order to be effectively transported in vivo; however, the surfactant accumulates in the body, which can cause various side effects, such as heart disease. Therefore, using new materials like alcohol for drug delivery will contribute to preventing the side effects caused by the surfactant. “The surfactant is used for delivering drugs, but it is difficult to be expelled from the body. This will cause various side effects, such as heart diseases in asthmatic patients,” said Professor Kim. “I hope that using new materials, like alcohol, will free people from these side effects.” (Marangoni-driven convection flow generated at the interface between water and alcohol, and the flow visualization results) - A drop of alcohol on a water surface - Comparison of mixing structures on the surface - Marangoni mixing flow under the free surface
Material-Independent Nanocoating Antimicrobial Spray Significantly Extends the Shelf Life of Produce
The edible coating on produce has drawn a great deal of attention in the food and agricultural industry. It could not only prolong postharvest shelf life of produce against external changes in the environment but also provide additional nutrients to be useful for human health. However, most versions of the coating have had intrinsic limitations in their practical application. First, highly specific interactions between coating materials and target surfaces are required for a stable and durable coating. Even further, the coating of bulk substrates, such as fruits, is time consuming or is not achievable in the conventional solution-based coating. In this respect, material-independent and rapid coating strategies are highly demanded. The research team led by Professor Insung Choi of the Department of Chemistry developed a sprayable nanocoating technique using plant-derived polyphenol that can be applied to any surface. This new nanocoating process can be completed in seconds to form nanometer-thick films, allowing for the coating of commodity goods, such as shoe insoles and fruits, in a controlled fashion. For example, spray-coated mandarin oranges and strawberries show significantly-prolonged postharvest shelf life, suggesting the practical potential in edible coatings of perishable produce. The technology has been patented and is currently being commercialized for widespread use as a means of preserving produce. The research results have recently been published in Scientific Reports on Aug 1. Polyphenols, a metabolite of photosynthesis, possess several hydroxyl groups and are found in a large number of plants showing excellent antioxidant properties. They have been widely used as a nontoxic food additive and are known to exhibit antibacterial, as well as potential anti-carcinogenic capabilities. Polyphenols can also be used with iron ions, which are naturally found in the body, to form an adhesive complex, which has been used in leather tanning, ink, etc. The research team combined these chemical properties of polyphenol-iron complexes with spray techniques to develop their nanocoating technology. Compared to conventional immersion coating methods, which dip substrates in specialized coating solutions, this spray technique can coat the select areas more quickly. The spray also prevents cross contamination, which is a big concern for immersion methods. The research team has showcased the spray’s ability to coat a variety of different materials, including metals, plastics, glass, as well as textile fabrics. The polyphenol complex has been used to form antifogging films on corrective lenses, as well as antifungal treatments for shoe soles, demonstrating the versatility of their technique. Furthermore, the spray has been used to coat produce with a naturally antibacterial, edible film. The coatings significantly improved the shelf life of tangerines and strawberries, preserving freshness beyond 28 days and 58 hours, respectively. (Uncoated fruit decomposed and became moldy under the same conditions). See the image below. a –I, II: Uncoated and coated tangerines incubated for 14 and 28 days in daily-life settings b –I: Uncoated and coated strawberries incubated for 58 hours in daily-life settings b –II: Statistical investigation of the resulting edibility. Professor Choi said, “Nanocoating technologies are still in their infancy, but they have untapped potential for exciting applications. As we have shown, nanocoatings can be easily adapted for several different uses, and the creative combination of existing nanomaterials and coating methods can synergize to unlock this potential.”
Cooperative Tumor Cell Membrane-Targeted Phototherapy
A KAIST research team led by Professor Ji-Ho Park in the Bio and Brain Engineering Department at KAIST developed a technology for the effective treatment of cancer by delivering synthetic receptors throughout tumor tissue. The study, led by Ph.D. candidate Heegon Kim, was published online in Nature Communications on June 19. Cancer targeted therapy generally refers to therapy targeting specific molecules that are involved in the growth and generation of cancer. The targeted delivery of therapeutics using targeting agents such as antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumors have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. To solve this problem, the team constructed a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumor cell membrane-selective localization of synthetic receptors to amplify the subsequent targeting of therapeutics. Here, synthetic and biological nanocomponents refer to liposomes and extracellular vesicles, respectively. The synthetic receptors are first delivered selectively to tumor cell membranes in the perivascular region using liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the synthetic receptors are transferred to neighboring cells and further spread throughout the tumor tissues where the molecular targets are limited. Hitchhiking extracellular vesicles for delivery of synthetic receptors was possible since extracellular vesicles, such as exosomes, mediate intercellular communications by transferring various biological components such as lipids, cytosolic proteins, and RNA through a membrane fusion process. They also play a supportive role in promoting tumor progression in that tumor-derived extracellular vesicles deliver oncogenic signals to normal host cells. The team showed that this tumor cell membrane-targeted delivery of synthetic receptors led to a uniform distribution of synthetic receptors throughout a tumor and subsequently led to enhanced phototherapeutic efficacy of the targeted photosensitizer. Professor Park said, “The cooperative tumor targeting system is expected to be applied in treating various diseases that are hard to target.” The research was funded by the Basic Science Research Program through the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, and the National R&D Program for Cancer Control funded by the Ministry for Health and Welfare. (Ph.D. candidates Hee Gon Kim (left) and Chanhee Oh) Figure 1. A schematic of a cooperative tumor targeting system via delivery of synthetic receptors. Figure 2. A confocal microscopic image of a tumor section after cooperative targeting by synthetic receptor delivery. Green and magenta represent vessels and therapeutic agents inside a tumor respectively.
Bio-based p-Xylene Oxidation into Terephthalic Acid by Engineered E.coli
KAIST researchers have established an efficient biocatalytic system to produce terephthalic acid (TPA) from p-xylene (pX). It will allow this industrially important bulk chemical to be made available in a more environmentally-friendly manner. The research team developed metabolically engineered Escherichia coli (E.coli) to biologically transform pX into TPA, a chemical necessary in the manufacturing of polyethylene terephthalate (PET). This biocatalysis system represents a greener and more efficient alternative to the traditional chemical methods for TPA production. This research, headed by Distinguished Professor Sang Yup Lee, was published in Nature Communications on May 31. The research team utilized a metabolic engineering and synthetic biology approach to develop a recombinant microorganism that can oxidize pX into TPA using microbial fermentation. TPA is a globally important chemical commodity for manufacturing PET. It can be applied to manufacture plastic bottles, clothing fibers, films, and many other products. Currently, TPA is produced from pX oxidation through an industrially well-known chemical process (with a typical TPA yield of over 95 mol%), which shows, however, such drawbacks as intensive energy requirements at high temperatures and pressure, usage of heavy metal catalysts, and the unavoidable byproduct formation of 4-carboxybenzaldehyde. The research team designed and constructed a synthetic metabolic pathway by incorporating the upper xylene degradation pathway of Pseudomonas putida F1 and the lower p-toluene sulfonate pathway of Comamonas testosteroni T-2, which successfully produced TPA from pX in small-scale cultures, with the formation of p-toluate (pTA) as the major byproduct. The team further optimized the pathway gene expression levels by using a synthetic biology toolkit, which gave the final engineered E. coli strain showing increased TPA production and the complete elimination of the byproduct. Using this best-performing strain, the team designed an elegant two-phase (aqueous/organic) fermentation system for TPA production on a larger scale, where pX was supplied in the organic phase. Through a number of optimization steps, the team ultimately achieved production of 13.3 g TPA from 8.8 g pX, which represented an extraordinary yield of 97 mol%. The team has developed a microbial biotechnology application which is reportedly the first successful example of the bio-based production of TPA from pX by the microbial fermentation of engineered E. coli. This bio-based TPA technology presents several advantages such as ambient reaction temperature and pressure, no use of heavy metals or other toxic chemicals, the removable of byproduct formation, and it is 100% environmentally compatible. Professor Lee said, “We presented promising biotechnology for producing large amounts of the commodity chemical TPA, which is used for PET manufacturing, through metabolically engineered gut bacterium. Our research is meaningful in that it demonstrates the feasibility of the biotechnological production of bulk chemicals, and if reproducible when up-scaled, it will represent a breakthrough in hydrocarbon bioconversions.” Ph.D. candidate Zi Wei Luo is the first author of this research (DOI:10.1038/ncomms15689).The research was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) of the Ministry of Science, ICT & Future Planning through the National Research Foundation of Korea. Figure: Biotransformation of pX into TPA by engineered E. coli. This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced TPA from pX. The engineered E. coli was developed through reconstituting a synthetic metabolic pathway for pX conversion to TPA and optimized for increased TPA yield and byproduct elimination. Two-phase partitioning fermentation system was developed for demonstrating the feasibility of large-scale production of TPA from pX using the engineered E. coli strains, where pX was supplied in the organic phase and TPA was produced in the aqueous phase.
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