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Creation of Synthetic Antibodies: Professor Hak Seong Kim
Synthetics antibodies which can replace antibodies from humans used as ingredients of medicines have been developed. It can increase the costs to 1/100 of the current costs and is much easier to develop. It is expected that the development period will be shortened from 10 years to 5. Prof. Hak Seong Kim from the Biology department of KAIST conducted a joint research with Prof. Dong Seob Kim to reconstruct proteins and has succeeded. The synthetic antibody displays much strength in terms of its productivity, structural formation, and bonding capability, and is thus regarded as an ideal protein. It can replace the antigens that are currently in use. It is expected that Korea will therefore be able to lead the world market for protein medicines which is a 192trillion won industry. The original antibody has been used for not only treating diseases, but also for various other applications in the fields of medical sciences and biology. However, it is produced through a very complex process involving the incubation of animal cells, and is therefore very expensive. Also, most antibodies are already patented by more developed countries, so a high royalty fee must be paid. Because of this, many countries including Korea has been concentrating on developing biosimilars copying the antibody medicines for which the patents have already expired. This causes Korea to be behind in the development of antibody protein pharmaceuticals. Prof. Kim’s research team has focused on the face that the protein existing in some eels are not antibodies but functions as one, and has been successful in developing a synthetic antibody. The synthetic antibody can be mass produced from the colon bacillus, which allows it to be produced at 1/100 the original cost. It is in a module structure which allows the structuring of the antibody into the desired structure, enabling it to be developed into a protein-based medicine within 5 years. Together with this, the coherence with the important antigens can be easily controlled, thus allowing for highly effective treatments, less side-effects, high security regarding heat and pH, and the immunogen levels being negligeable. This suggests a very high rate of the antibody being converted into a protein based medication. The synthetic antibody technology has been tested as a sample for the cure for lung diseases and rheumatism and has been proven to be appropriate. Animal testing will be conducted soon. Prof Kim said “The original antibodies had a small area allowing the bonding with antibodies, creating barriers for raising bonding strength and structuring. The newly created antibody carries only the strengths and will become a new protein based medicine purely created by Korean technology to replace the antibodies currently used in medications.” Furthermore, he added that, “The synthesized antibody structuring and designing technology will be widely used in the areas of detecting, diagnosing, and analyzing diseases.” At the same time, this research result has been published in the Feb 10th issue of the PNAS, and has been supported by the future promising pioneer business program held by the Ministry of Education and Technology.
Bioengineers develop a new strategy for accurate prediction of cellular metabolic fluxes
A team of pioneering South Korean scientists has developed a new strategy for accurately predicting cellular metabolic fluxes under various genotypic and environmental conditions. This groundbreaking research is published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) on August 2, 2010. To understand cellular metabolism and predict its metabolic capability at systems-level, systems biological analysis by modeling and simulation of metabolic network plays an important role. The team from the Korea Advanced Institute of Science and Technology (KAIST), led by Distinguished Professor Sang Yup Lee, focused their research on the development of a new strategy for more accurate prediction of cellular metabolism. “For strain improvement, biologists have made every effort to understand the global picture of biological systems and investigate the changes of all metabolic fluxes of the system under changing genotypic and environmental conditions,” said Lee. The accumulation of omics data, including genome, transcriptome, proteome, metabolome, and fluxome, provides an opportunity to understand the cellular physiology and metabolic characteristics at systems-level. With the availability of the fully annotated genome sequence, the genome-scale in silico (means “performed on computer or via computer simulation.”) metabolic models for a number of organisms have been successfully developed to improve our understanding on these biological systems. With these advances, the development of new simulation methods to analyze and integrate systematically large amounts of biological data and predict cellular metabolic capability for systems biological analysis is important. Information used to reconstruct the genome-scale in silico cell is not yet complete, which can make the simulation results different from the physiological performances of the real cell. Thus, additional information and procedures, such as providing additional constraints (constraint: a term to exclude incorrect metabolic fluxes by restricting the solution space of in silico cell) to the model, are often incorporated to improve the accuracy of the in silico cell. By employing information generated from the genome sequence and annotation, the KAIST team developed a new set of constraints, called Grouping Reaction (GR) constraints, to accurately predict metabolic fluxes. Based on the genomic information, functionally related reactions were organized into different groups. These groups were considered for the generation of GR constraints, as condition- and objective function- independent constraints. Since the method developed in this study does not require complex information but only the genome sequence and annotation, this strategy can be applied to any organism with a completely annotated genome sequence. “As we become increasingly concerned with environmental problems and the limits of fossil resources, bio-based production of chemicals from renewable biomass has been receiving great attention. Systems biological analysis by modeling and simulation of biological systems, to understand cellular metabolism and identify the targets for the strain improvement, has provided a new paradigm for developing successful bioprocesses,” concluded Lee. This new strategy for predicting cellular metabolism is expected to contribute to more accurate determination of cellular metabolic characteristics, and consequently to the development of metabolic engineering strategies for the efficient production of important industrial products and identification of new drug targets in pathogens.”
Native-like Spider Silk Produced in Metabolically Engineered Bacterium
Microscopic picture of 285 kilodalton recombinant spider silk fiber Researchers have long envied spiders’ ability to manufacture silk that is light-weighted while as strong and tough as steel or Kevlar. Indeed, finer than human hair, five times stronger by weight than steel, and three times tougher than the top quality man-made fiber Kevlar, spider dragline silk is an ideal material for numerous applications. Suggested industrial applications have ranged from parachute cords and protective clothing to composite materials in aircrafts. Also, many biomedical applications are envisioned due to its biocompatibility and biodegradability. Unfortunately, natural dragline silk cannot be conveniently obtained by farming spiders because they are highly territorial and aggressive. To develop a more sustainable process, can scientists mass-produce artificial silk while maintaining the amazing properties of native silk? That is something Sang Yup Lee at the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, the Republic of Korea, and his collaborators, Professor Young Hwan Park at Seoul National University and Professor David Kaplan at Tufts University, wanted to figure out. Their method is very similar to what spiders essentially do: first, expression of recombinant silk proteins; second, making the soluble silk proteins into water-insoluble fibers through spinning. For the successful expression of high molecular weight spider silk protein, Professor Lee and his colleagues pieced together the silk gene from chemically synthesized oligonucleotides, and then inserted it into the expression host (in this case, an industrially safe bacterium Escherichia coli which is normally found in our gut). Initially, the bacterium refused to the challenging task of producing high molecular weight spider silk protein due to the unique characteristics of the protein, such as extremely large size, repetitive nature of the protein structure, and biased abundance of a particular amino acid glycine. “To make E. coli synthesize this ultra high molecular weight (as big as 285 kilodalton) spider silk protein having highly repetitive amino acid sequence, we helped E. coli overcome the difficulties by systems metabolic engineering,” says Sang Yup Lee, Distinguished Professor of KAIST, who led this project. His team boosted the pool of glycyl-tRNA, the major building block of spider silk protein synthesis. “We could obtain appreciable expression of the 285 kilodalton spider silk protein, which is the largest recombinant silk protein ever produced in E. coli. That was really incredible.” says Dr. Xia. But this was only step one. The KAIST team performed high-cell-density cultures for mass production of the recombinant spider silk protein. Then, the team developed a simple, easy to scale-up purification process for the recombinant spider silk protein. The purified spider silk protein could be spun into beautiful silk fiber. To study the mechanical properties of the artificial spider silk, the researchers determined tenacity, elongation, and Young’s modulus, the three critical mechanical parameters that represent a fiber’s strength, extensibility, and stiffness. Importantly, the artificial fiber displayed the tenacity, elongation, and Young’s modulus of 508 MPa, 15%, and 21 GPa, respectively, which are comparable to those of the native spider silk. “We have offered an overall platform for mass production of native-like spider dragline silk. This platform would enable us to have broader industrial and biomedical applications for spider silk. Moreover, many other silk-like biomaterials such as elastin, collagen, byssus, resilin, and other repetitive proteins have similar features to spider silk protein. Thus, our platform should also be useful for their efficient bio-based production and applications,” concludes Professor Lee. This work is published on July 26 in the Proceedings of the National Academy of Sciences (PNAS) online.
KAIST Professor Finds Paradox in Human Behaviors on Road
-Strange as it might seem, closing roads can cut delays A new route opened to ease traffic jam, but commuting time has not been reduced.Conversely, motorists reached their destinations in shorter times after a big street was closed. These paradoxical phenomena are the result of human selfishness, according to recent findings of a research team led by a KAIST physics professor. Prof. Ha-Woong Jeong, 40, at the Department of Physics, conducted a joint research with a team from Santa Fe Institute of the U.S. to analyze the behaviors of drivers in Boston, New York and London. Their study found that when individual drivers, fed with traffic information via various kinds of media, try to choose the quickest route, it can cause delays for others and even worsen congestion. Prof. Jeong and his group"s study will be published in the Sept. 18 edition of the authoritative Physical Review Letters. The London-based Economist magazine introduced Prof. Jeong"s finding in its latest edition. Prof. Jeong, a pioneer in the study of "complex system," has published more than 70 research papers in the world"s leading science journals, including Nature, PNAS and Physical Review Letters. "Initially, my study was to reduce annoyance from traffic jam during rush hours," Prof. Jeong said. "Ultimately, it is purposed to eliminate inefficiency located in various corners of social activities, with the help of the network science." The Economist article read (in part): "...when individual drivers each try to choose the quickest route it can cause delays for others and even increase hold-ups in the entire road network. "The physicists give a simplified example of how this can happen: trying to reach a destination either by using a short but narrow bridge or a longer but wide motorway. In their hypothetical case, the combined travel time of all the drivers is minimized if half use the bridge and half the motorway. But that is not what happens. Some drivers will switch to the bridge to shorten their commute, but as the traffic builds up there the motorway starts to look like a better bet, so some switch back. Eventually the traffic flow on the two routes settles into what game theory calls a Nash equilibrium, named after John Nash, the mathematician who described it. This is the point where no individual driver could arrive any faster by switching routes. "The researchers looked at how this equilibrium could arise if travelling across Boston from Harvard Square to Boston Common. They analysed 246 different links in the road network that could be used for the journey and calculated traffic flows at different volumes to produce what they call a “price of anarchy” (POA). This is the ratio of the total cost of the Nash equilibrium to the total cost of an optimal traffic flow directed by an omniscient traffic controller. In Boston they found that at high traffic levels drivers face a POA which results in journey times 30% longer than if motorists were co-ordinated into an optimal traffic flow. Much the same thing was found in London (a POA of up to 24% for journeys between Borough and Farringdon Underground stations) and New York (a POA of up to 28% from Washington Market Park to Queens Midtown Tunnel). "Modifying the road network could reduce delays. And contrary to popular belief, a simple way to do that might be to close certain roads. This is known as Braess’s paradox, after another mathematician, Dietrich Braess, who found that adding extra capacity to a network can sometimes reduce its overall efficiency. "In Boston the group looked to see if the paradox could be created by closing any of the 246 links. In 240 cases their analysis showed that a closure increased traffic problems. But closing any one of the remaining six streets reduced the POA of the new Nash equilibrium. Much the same thing was found in London and New York. More work needs to be done to understand these effects, say the researchers. But even so, planners should note that there is now evidence that even a well intentioned new road may make traffic jams worse."
Maximum Yield Amino Acid-Producing Microorganism Developed with use of System Biotechnology
Maximum Yield Amino Acid-Producing Microorganism Developed with use of System Biotechnology A team led by Sang-Yup Lee, a distinguished professor of Chemical and Biomolecular Engineering and chair professor of LG Chemical, has succeeded in developing maximum yield L-valine-producing microorganism by using System Biotechnology methods. The research results will be published at the April fourth week (April 23 - 27) edition of the Proceedings of the National Academy of Sciences (PNAS) of the USA. Prof. Lee’s team has developed maximum yield amino acid-producing microorganism (target substance of L-valine, an essential amino-acid) by using microorganism E cell system and simulation methods. His team produced initial producing microorganism by selectively operating necessary parts in colon bacillus genome and excavated preliminary target gene which is to newly be operated through transcriptome analysis using DNA chips. Then they performed a great amount of gene deletion experiment on computer by using MBEL979, E-cells of colon bacillus, and excavated secondary engineering targets. And they finally succeeded in developing maximum yield valine-producing microorganism that can extract 37.8 grams of valine from 100 grams of glucose by applying experiment results to the actual development of microorganism so as to achieve the optimization of metabolic flux in cells, Prof. Lee said, “Since successfully used for the development of microorganism on a systematic system level, system biotechnology methods are expected to significantly contribute to the development of all biotechnology-relevant industries. At the beginning, we had huge obstacles in fusing IT and BT, but my team mates cleverly overcame such obstacles, hence I’m very proud of them.” The producing microorganism and its developing methods are pending international applications (PCT).
Professor Seong-Ihl Woo Develops New High-Speed Research Method
Professor Seong-Ihl Woo Develops New High-Speed Research Method Reduce research periods and expenses for thin film materials several ten times Posted on the online version of Proceedings of National Academy of Sciences of the United States of America (PNAS) on January 9 A team led by Seong-Ihl Woo, a professor of KAIST Department of Chemical & Biomolecular Engineering and the director of the Center for Ultramicrochemical Process Systems, has developed a high-speed research method that can maximize research performances and posted the relevant contents on the online version of Proceedings of National Academy of Sciences of the United States of America (PNAS), a distinguished scientific journal, on January 9, 2007. Professor Woo’s team has developed a high-speed research method that can fabricate several tens or several thousands of thin films with different compositions (mixing ratio) at the same time and carry out structural analysis and performance evaluation more than ten times faster and accurately, which leads to the shortening of the research processes of thin film materials. This is an epoch-making method that can reduce research periods and expenses several ten times or more, compared to the previous methods. The qualities of final products of electronic materials, displays, and semi-conductors depend on the features of thin film materials. Averagely, it takes about two weeks or longer to fabricate a functional thin film and analyze and evaluate its performances. In order to fabricate thin film materials in need successfully, more than several thousand times of tests are required. The existing thin film-fabricating equipment is expensive one demanding high-degree vacuum, such as chemical vapor deposition, sputtering, physical vapor deposition, laser evaporation, and so on. In order to fabricate thin films of various compositions with this equipment, a several million won-worth target (solid-state raw material) and precursors (volatile organic metal compound) pricing several hundreds won per gram are required. Therefore, huge amount of experiment expense is demanded for fabrication of several ten thousands of thin films with various compositions. Professor Woo’s team has developed ‘combinatorial droplet chemical deposition’ equipment, which does not demand high-degree vacuum and is automated by computers and robots, by using a new high-speed research measure. The equipment is priced at about 1/5 of the existing equipment and easy for maintenance. This equipment uses cheap reagents, instead of expensive raw materials. Reagents necessary to form required compositions are dissolved in water or proper solvents, and then applied by high frequencies to make several micrometer-scaled droplets (fine liquid droplet). Theses droplets are moved by nitrogen and dropped onto a substrate, which is to be fabricated into a thin film, and then subsequent thermal treatment is applied to the substrate to fabricate a thin film of required composition. At this moment, several tens or several hundreds of thin films with various compositions can be fabricated at the same time by reducing the size of thin film specimens into millimeter scale with the use of shade mask and adjusting vaporization time with masks, the moving speed of which can be adjusted. The expenses for materials necessary for the fabrication of thin films with this equipment amount to several ten thousands won per 100 grams, which is in the range of 1/100 and 1/10 of the previous methods, and the research period can be shortened into one of several tenth. “If this new method is applied to the development of elements in the fields of core energy, material and health, which have not been discovered by the existing research methods so far, as well as researches in thin film material field, substantial effects will be brought,” said Professor Woo. ‘Combinatorial droplet chemical vaporization’ equipment is pending a domestic patent application and international patent applications at Japan and Germany. This equipment will be produced by order and provided to general researchers.
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