BIO
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New drug targeting method for microbial pathogens developed using in silico cell
A ripple effect is expected on the new antibacterial discovery using “in silico” cells
Featured as a journal cover paper of Molecular BioSystems
A research team of Distinguished Professor Sang Yup Lee at KAIST recently constructed an in silico cell of a microbial pathogen that is resistant to antibiotics and developed a new drug targeting method that could effectively disrupt the pathogen"s growth using the in silico cell.
Hyun Uk Kim, a graduate research assistant at the Department of Chemical and Biomolecular Engineering, KAIST, conducted this study as a part of his thesis research, and the study was featured as a journal cover paper in the February issue of Molecular BioSystems this year, published by The Royal Society of Chemistry based in Europe.
It was relatively easy to treat infectious microbes using antibiotics in the past. However, the overdose of antibiotics has caused pathogens to increase their resistance to various antibiotics, and it has become more difficult to cure infectious diseases these days.
A representative microbial pathogen is Acinetobacter baumannaii. Originally isolated from soils and water, this microorganism did not have resistance to antibiotics, and hence it was easy to eradicate them if infected. However, within a decade, this miroorganism has transformed into a dreadful super-bacterium resistant to antibiotics and caused many casualties among the U.S. and French soldiers who were injured from the recent Iraqi war and infected with Acinetobacter baumannaii.
Professor Lee’s group constructed an in silico cell of this A. baumannii by computationally collecting, integrating, and analyzing the biological information of the bacterium, scattered over various databases and literatures, in order to study this organism"s genomic features and system-wide metabolic characteristics. Furthermore, they employed this in silico cell for integrative approaches, including several network analysis and analysis of essential reactions and metabolites, to predict drug targets that effectively disrupt the pathogen"s growth. Final drug targets are the ones that selectively kill pathogens without harming human body.
Here, essential reactions refer to enzymatic reactions required for normal metabolic functioning in organisms, while essential metabolites indicate chemical compounds required in the metabolism for proper functioning, and their removal brings about the effect of simultaneously disrupting their associated enzymes that interact with them.
This study attempted to predict highly reliable drug targets by systematically scanning biological components, including metabolic genes, enzymatic reactions, that constitute an in silico cell in a short period of time.
This research achievement is highly regarded as it, for the first time, systematically scanned essential metabolites for the effective drug targets using the concept of systems biology, and paved the way for a new antibacterial discovery. This study is also expected to contribute to elucidating the infectious mechanism caused by pathogens.
"Although tons of genomic information is poured in at this moment, application research that efficiently converts this preliminary information into actually useful information is still lagged behind. In this regard, this study is meaningful in that medically useful information is generated from the genomic information of Acinetobacter baumannii," says Professor Lee. "In particular, development of this organism"s in silico cell allows generation of new knowledge regarding essential genes and enzymatic reactions under specific conditions," he added.
This study was supported by the Korean Systems Biology Project of the Ministry of Education, Science and Technology, and the patent for the development of in silico cells of microbial pathogens and drug targeting methods has been filed.
[Picture 1 Cells in silico]
[Picture 2 A process of generating drug targets without harming human body while effectively disrupting the growth of a pathogen, after predicting metabolites from in silico cells]
2010.04.05 View 16798 -
Prof. Lee"s Team Succeeds in Producing Plastics Without Use of Fossil Fuels
A team of scientists led by Prof. Sang-Yup Lee of the Department of Biological Sciences at KAIST have succeeded in producing the polymers used for everyday plastics through bioengineering, rather than through the use of fossil fuel based chemicals, the university authorities said on Tuesday (Nov. 24).
This groundbreaking research, which may now allow for the production of environmentally conscious plastics, has been published in two papers in the journal Biotechnology and Bioengineering.
Polymers are molecules found in everyday life in the form of plastics and rubbers. The team consisted of scientists from KAIST and Korean chemical company LG Chem focused their research on polylactic acid (PLA), a bio-based polymer which holds the key to producing plastics through natural and renewable resources.
"The polyesters and other polymers we use everyday are mostly derived from fossil oils made through the refinery or chemical process," said Lee. "The idea of producing polymers from renewable biomass has attracted much attention due to the increasing concerns of environmental problems and the limited nature of fossil resources. PLA is considered a good alternative to petroleum based plastics as it is both biodegradable and has a low toxicity to humans."
Until now PLA has been produced in a two-step fermentation and chemical process of polymerization, which is both complex and expensive. Now, through the use of a metabolically engineered strain of E.coli, the team has developed a one-stage process which produces polylactic acid and its copolymers through direct fermentation. This makes the renewable production of PLA and lactate-containing copolymers cheaper and more commercially viable.
"By developing a strategy which combines metabolic engineering and enzyme engineering, we"ve developed an efficient bio-based one-step production process for PLA and its copolymers," said Lee. "This means that a developed E. coli strain is now capable of efficiently producing unnatural polymers, through a one-step fermentation process,"
This combined approach of systems-level metabolic engineering and enzyme engineering now allows for the production of polymer and polyester based products through direct microbial fermentation of renewable resources.
"Global warming and other environmental problems are urging us to develop sustainable processes based on renewable resources," concluded Lee. "This new strategy should be generally useful for developing other engineered organisms capable of producing various unnatural polymers by direct fermentation from renewable resources".
2009.11.30 View 15102 -
Prof. Sang-Yup Lee Founding Member of Board of Editors of mBop
Prof. Sang-Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST has been appointed as one of the founding board of editors of the mBio which will be launched next year, the university reported on Friday (Nov. 20).
mBio is the American Society for Microbiology"s first all-online, open access journal which will be launched in next May. According to the mBio website, the journal"s scope "will reflect the enormity of the microbial world, a highly interconnected biosphere where microbes interact with living and non-living matter to produce outcomes that range from symbiosis to pathogenesis, energy acquisition and conversion, climate change, geologic change, food and drug production, and even animal behavioral change."
Prof. Lee, LG Chem Chair Professor, is currently the Dean of the College of Life Science and Bioengineering and director of the Center for Systems and Synthetic Biotechnology. He received his B.S. in Chemical Engineering from Seoul National Univeristy in Korea and his M.S. and Ph.D. in Chemical Engineering from Northwestern University.
As of September 2009, he has published 298 journal papers and has more than 440 patents either registered or applied. Also, he has published 47 books/book chapters, "Systems Biology and Biotechnology of Escherichia Coli" being the latest.
His research interests are systems biology and biotechnology, industrial biotechnology, metabolic engineering, synthetic biology and nanobiotechnology. In particular, he has pioneered systems metabolic engineering, which integrates systems biology with metabolic engineering, for the development of micropoganisms possessing superior properties for industrial applications.
2009.11.20 View 12688 -
KAIST, CJ Sign MOU for Joint Research in Fundamental Technologies
KAIST and CJ Corporation, Korea"s leading foodstuff maker, have reached an agreement for an enhanced industry-academy cooperation in the biotechnology area, the university authorities said on Tuesday (Nov. 10).
KAIST President Nam-Pyo Suh signed a memorandum of understanding with Kim Jin-soo, CEO of CJ, at the KAIST campus on Tuesday (Nov. 10).
Under the agreement, KAIST and CJ will cooperate in nurturing elite research manpower and conducting joint researches in fundamental technologies. Specifically, CJ researchers will suggest research subjects linked with doctorate programs to KAIST, and once these subjects are accepted by KAIST, CJ researchers will conduct research under the guidance of KAIST professors to get doctorate degrees. All the costs including research expenses incurred during the program will be provided by CJ.
The agreement also calls for CJ to provide funding for the research subjects it selected among the ones suggested by KAIST"s biotechnology professors.
CJ CEO Jin-Soo Kim said: "Through the joint researches with KAIST which has the highest research capabilities, CJ can strengthen basic research capabilities and secure elite research manpower. We hope that the KAIST-CJ partnership will become a successful model for cooperation between industry and academia."
2009.11.11 View 12443 -
Board Chairman Chung Makes First Visit to Building Named After Him
Moon-Soul Chung, chairman of the KAIST board of trustees, visited the building built with his donation on Monday (Oct. 19) for the first time since he made the deed of gift eight years ago, university authorities said on Monday (Oct. 19).
In 2000, Chung, founder and former CEO of Mirae Corp, manufacturer of semiconductor testing equipment, announced retirement and handed over the presidency of his company to one of his managing directors. One year later in 2001, he donated 30 billion won, then equivalent to $30 million, to KAIST. It was by then the largest amount given by a single donor.
The major part of his donation went to constructing a building for the newly-established Department of Bio and Brain Engineering, and it was named after him. However, Chung did not attend the ground-breaking and dedication ceremonies, saying that he would not enter the building until KAIST achieved a breakthrough technology which can inject a hope to Koreans.
On his first visit to the building, he was briefed on the major research outcomes of the department over the past seven years, which were highlighted by the recent invention of an apparatus for measuring perfusion rate of legs. A KAIST team headed by Prof. Chul-Hee Choi invented a light leakage prevention unit including a light emitting device for radiating light having a certain wavelength onto a living body injected with Indocyanine Green (ICG).
According to Prof. Choi, the invention relates to an apparatus for measuring the perfusion rate of legs. The invention also includes a light leakage prevention housing formed to prevent transmission of external light.
Chung expressing satisfaction with the achievements and encouraged professors, researchers and students working at the Moon-Soul Chung Building.
2009.10.20 View 14247 -
Prof. Cho Elected Editor-in-Chief of Systems Biology
Prof. Kwang-Hyun Cho of Department of Bio and Brain Engineering at KAIST has been recently elected editor-in-chief of the Systems Biology, an international journal published by the London-based Institution of Engineering and Technology (IET), the university authorities said on Wednesday (Sept. 23)
By the year 2012, Cho will oversee the editorial process of the journal covering intra- and inter-cellular dynamics, using systems- and signal-oriented approaches. IET, one of the world"s leading professional societies for the engineering and technology community, has a worldwide membership of more than 150,000.
Prof. Cho"s research interests cover the areas of systems science with bio-medical applications including systems biology and bio-inspired engineering based on molecular systems biology. He is currently an editorial board member of Systems and Synthetic Biology (Springer, Netherlands, from 2006), BMC Systems Biology (BMC, London, U.K., from 2007), Gene Regulation and Systems Biology (Libertas Academica, New Zealand, from 2007), and Bulletin of Mathematical Biology (Springer, New York, from 2008), and an editorial advisory board member of Molecular BioSystems (The Royal Society of Chemistry, U.K.).
2009.09.24 View 16373 -
Prof. Lee"s Team Pioneers Biotechnological Production of Chemical Using Renewable Materials
A research team led by Prof. Sang-Yup Lee of the Bio and Brain Engineering Department at KAIST has succeeded in engineering the bacterium E. coli to produce the industrial chemical putrescine, university authorities said on Monday (Aug. 31).
Putrescine, a four carbon chain diamine, is an important platform chemical with a wide range of applications for the pharmaceutical, agrochemical and chemical industries. It is currently used to synthesize nylon-4,6, a widely used engineering plastic.
The research result, published in the Biotechnology and Bioengineering journal, proviDrdes a renewable alternative to the traditional process using fossil fuels.
Currently the production of putrescine on an industrial scale relies on chemical synthesis, which requires non-renewable petrochemicals and expensive catalyst systems. This process is highly toxic and flammable with potentially severe repercussions for both the environment and human health.
"For the first time we have developed a metabolically engineered E. coli strain that efficiently produces putrescine," said Professor Lee. "The development of a bio-refinery for chemicals and materials is very important in a world where dependency on fossil fuels is an increasing concern."
The team developed a strain of E.coli capable of producing putrescine through metabolic engineering. This is where a cell"s metabolic and regulatory networks are enhanced in order to increase production of a needed material.
First the team weakened or deleted competing metabolic pathways within the E. coli strain before deleting pathways which cause putrescine degradation. They also amplified the crucial enzyme Spec C, which converts the chemical ornithine into putrescine. Finally the putrescine exporter, which allows excretion of intracellularly made putrescine, was engineered while a global regulator was engineered to further increase the concentration of putrescine. The final result of this process was an engineered E.coli strain which produced 24.2 g of putrescine per litre.
However, as it was believed that putrescine is toxic to microorganisms the team had to study putrescine tolerance in E.coli before it could be engineered to overproduce the chemical to the levels needed for industrial production.
The results revealed that E. coli can tolerate at least 0.5 M of putrescine, which is tenfold higher than the usual concentration in the cell. This level of tolerance was an important surprise as it means that E. coli can be engineered to overproduce putrescine to industrially competitive levels.
"The previously expected toxicity of putrescine may explain why its microbial production has been overlooked," said Lee. "Now a metabolically engineered E. coli strain has been developed which is capable of efficiently producing putrescine using renewable methods to an industrial level. This metabolic engineering framework should be useful for developing metabolically engineered microorganisms for the efficient production of other chemicals from renewable resources," he added.
2009.09.01 View 14491 -
KAIST College of Life Sciences and Bioengineering Signs MOU with Harvard
KAIST’s College of Life Sciences and Bioengineering recently signed a memorandum of understanding (MOU) with Harvard University’s Center for Brain Science on July 20, which will allow for joint research and exchange in researchers between the two institutions.
Headed by Director Kenneth Blum, Harvard’s Center for Brain Science leads the world in brain-related research. The new MOU will allow for research cooperation, exchanges of professors, researchers, and students, joint usage of infrastructure and research materials, and finally, sharing of research assignments.
The Dean of the College of Life Sciences and Bioengineering Sang Yup Lee, who concerted efforts to form the MOU said, “This agreement will bring together two of the world’s leading brain-related research teams, and I hope that combining their expertise will bring great advances in brain science and engineering.
KAIST’s College of Life Science and Bioengineering, which is known for its creative interdisciplinary research, is producing exemplary research results in the field of brain science from its Biological Sciences and Bio and Brain Engineering departments.
In addition to cooperation with Harvard, KAIST has also formed partnerships with Emory University, Japan’s RIKEN Brain Institute, and Germany’s Max Planck Institute. Not only does it have a worldwide network pertaining to brain research, but KAIST has also engaged in cooperative research with prominent domestic institutions such as, Asan Medical Center, the Korea Research Institute of Bioscience and Biotechnology, the Korea Research Institute of Standards and Science, and the SK Corporation. Through these connections, KAIST has managed to lead in mutually cooperative brain interdisciplinary research.
2009.08.10 View 16591
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KAIST Professor Sang-Yup Lee Chair of International Metabolic Engineering Conference Due Next Year
KAIST distinguished professor Sang-Yup Lee was named to chair the 17th Metabolic Engineering Conference which will convene on Jeju Island, Korea, next year, under the theme of "Metabolic Engineering for Green Growth." It was decided at the 16th Biochemical Engineering Conference held in Burlington, Vermont, on July 5-9.
Metabolic Engineering Conference in 2010 will not only involve presentations and discussions about metabolic engineering, but will inaugurate the “World Council on Industrial Biotechnology,” which will bring together global corporations and the world’s experts in industrial biochemical engineering, according to sources at KAIST.
A KAIST official commented, “The fact that the Metabolic Engineering Conference is to be held here [in Korea] proves that Korea is being acknowledged as a key player in this field.”
As the world faces the depletion of fossil fuels and environmental pollution, nations are showing increasing interest in industrial biochemical alternatives, such as microscopic organisms or new chemicals, to solve their problems. In addition, efficient production of biochemical materials and bio-fuels using microbes is deemed vital for the future.
“The Korean government has become a model to other countries thanks to its leadership in carrying out the ‘Green Growth’ policy,” Professor Sang-Yup Lee said. He stated that KAIST is recognized for its research in advanced biochemical material and fuel production methods.
“Green Growth,” a concept first developed by ESCAP, the UN agency working for social and economic cooperation in Asia and the Pacific, aims to achieve sustainable economic growth without destroying the environment.
Ref. Department of Biochemical Engineering, Metabolic and BioMolecular Engineering Lab, KAIST
2009.07.17 View 13730 -
Prof. Cho Appointed Editor-in-Chief of Systems Biology Encyclopedia
Prof. Kwang-Hyun Cho of the Department of Bio and Brain Engineering, KAIST, has been appointed as the editor-in-chief of the Encyclopedia of Systems Biology which is currently in development by Springer, a New York-based publishing company, university authorities said on Monday (July 6).
Prof. Cho will share the position with three other eminent scholars from Britain, Germany and the United States. Cho will be responsible for selecting editorial members for each section of the Encyclopedia and overseeing the overall editorial process.
The Encyclopedia of Systems Biology is a multi-volume reference compilation of the research outcomes in the field of systems biology all over the world. The ESB will consist of alphabetically ordered description of systems biology concepts and is envisaged to ultimately comprise 6-12 volumes. Publication of the Encyclopedia is scheduled for 2011.
2009.07.08 View 13506 -
KAIST Prof. Park Selected as Winner of Clemson Award
Professor Tae-Gwan Park of the Department of Biological Sciences, KAIST, was chosen as the winner of the 2009 Clemson Award for Fundamental Research, university authorities said on Tuesday (April 7).
The award is the highest recognition of the Society for Biomaterials, an international organization of more than 3,000 members that promotes research in the field of biomaterials. Prof. Park is cited for his outstanding achievements in interdisciplinary research covering gene transferring, gene therapy and neogenesis. It is rare for a non-U.S. national to win the prize in the 36-year history of the award.
The award will be given to Professor Park at the Annual Meeting of the society which will be held in San Antonio, Texas, on April 22.
2009.04.09 View 12858 -
Workshop on Biomedical IC to Be Held on March 26
KAIST will hold a workshop on "biomedical IC for future healthcare system" on March 26 at a lecture room of the School of Electrical Engineering & Computer Science. The workshop is organized by SEECS and the Korean Institute of Next Generation Computing.
At the workshop, a variety of new technologies expected to expedite the development of biomedical systems will be presented. KAIST Prof. Hoi-Jun Yoo will speak on the "body channel communication" using the human body as the signal transmission medium and Dr. Seung-Hwan Kim of Electronics and Telecommunications Research Institute (ETRI) on a wearable vital sign monitoring system.
Other subjects are CMOS (complementary metal-oxide semiconductor) fully electronic biosensor for biomolecular detection to be presented by KAIST Prof. Gyu-Hyeong Cho; nerve interface and IC (integrated circuit) system design by KAIST Prof. Yoon-gi Nam; design of neural recording and stimulation IC using time-varying magnetic field by KAIST Prof. Seong-Hwan Cho; low power multi-core digital signal processor for hearing aid by Dong-Wook Kim, senior researcher at the Samsung Advanced Institute of Technology; and a non-contact cardiac sensor by KAIST Prof. Seung-Chul Hong.
With the advent of the ageing society, medical expenses of the elderly people are rapidly increasing. As a way to address the issue, interests are growing in "ubiquitous healthcare," a technology that uses a large number of environmental and patient sensors and actuators to monitor and improve patients’ physical and mental condition.
The upcoming workshop is the first academic event on biomedical integrated chips to be held in Korea. The workshop will provide a valuable opportunity for experts in biomedical area to get together and examine the present status of Korean biomedical area and discuss about its future, KAIST officials said.
2009.03.20 View 18518