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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.”
The thermal fluctuation and elasticity of cell membranes, lipid vesicles, interacting with pore-forming peptides were reported by a research team at KAIST.
A research team from KAIST, consisted of Sung-Min Choi, Professor of Nuclear and Quantum Engineering Department, and Ji-Hwan Lee, a doctoral student in the Department, published a paper on the “thermal fluctuation and elasticity of lipid vesicles interacting with pore-forming peptides.” The paper was carried by Physical Review Letters, an internationally renowned peer-review journal on physics on July 16, 2010. Cell membranes, which consist of lipid bilayers, play important roles in cells as barriers to maintain concentrations and matrices to host membrane proteins. During cellular processes such as cell fission and fusion, the cell membranes undergo various morphological changes governed by the interplay between protein and lipid membranes. There have been many theoretical and experimental approaches to understand cellular processes driven by protein-lipid membrane interactions. However, it is not fully established how the membrane elastic properties, which play an important role in membrane deformation, are affected by the protein-membrane interactions. Antimicrobial peptides are one of the most common examples of proteins that modify membrane morphology. While the pore-forming mechanisms of antimicrobial peptides in lipid bilayers have been widely investigated, there have been only a few attempts to understand the mechanisms in terms of membrane elastic properties. In particular, the effects of pore formation on the membrane fluctuation and elastic properties, which provide key information to understand the mechanism of antimicrobial peptide activity, have not been reported yet. The research team reports the thermal fluctuation and elasticity of lipid vesicles interacting with pore-forming peptides, which were measured by neutron spin-echo spectroscopy. The results of this study are expected to pay an important role in understanding the elastic behavior and morphological changes of cell membranes induced by protein-membrane interactions, and may provide new insights for developing new theoretical models for membrane fluctuations which include the membrane mediated interaction between protein patches. (a) (b) Figure (a) Schematics for bound melittin and pores in lipid bilayers (b) P NMR signal ratio (with/without Mn2+) of DOPC LUV-melittin vs P/L at 30˚C. The dashed line is a guide for eyes.
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]
KAIST Research Team Identified Promising New Source to Obtain Stem Cells
KAIST Research Team Identified Promising New Source to Obtain Stem Cells A research team at KAIST led by Professor Gou-Young Koh, M.D. and Ph.D., of the Department of Biological Sciences, has found evidence that fat tissue, known as adipose tissue, may be a promising new source of valuable and easy-to-obtain regenerative cells called hematopoietic stem and progenitor cells (HSPCs). HSPCs are adult stem cells that have the ability to generate and develop into many different kinds of cells. They are now used to repair damaged tissues and are being studied for their potential to treat a vast array of chronic and degenerative conditions such as leukemia. Mostly found in bone marrow but with a limited quantity, HSPCs are hard to cultivate in vitro, thus becoming an obstacle to use them for research and therapeutic purposes. Within the adipose tissue is a special cell population known as the stromal vascular fraction (SVF), which share similar properties to those in the bone marrow. Cells in the bone marrow and SVF have the ability to differentiate into several cell types. In addition, both adipose and bone marrow offer similar environments for optimal stem cell growth and reproduction. Given the fact that adipose and bone marrow tissues share similar properties, Dr. Koh and his team conducted a research, injecting granulocyte colony-stimulating factor (G-CSF), a growth hormone used to encourage the development of stem cells, into an adipose tissue of a mouse whose bone marrow is damaged. As a result, the team has found that the SVF derived from adipose tissue contains functional HSPCs capable of generating hematopoietic (blood-forming) cells to repair the damaged bone morrow. The Ministry of Education, Science and Technology nominated the KAIST research as one of its sponsoring 21st Century Frontier R&D Programs. Director Dong-Wook Kim of Stem Cell Research Center (SCRS) that oversees the KAIST team expressed a possibility to use the adipose tissue as an alternative source to obtain stem cells for regeneration medicine. Dr. Koh also said, “It’s been a well known method to extract HSPCs from the bone morrow or blood, but it’s the first time to identify adipose tissue, before considered useless, as a new possible supplier for functional and transplantable HSPCs.” The study results have received an important recognition from the academia—the American Society of Hematology published the research as a main article in its official journal, Blood, for the February 4th, 2010 issue, which is the most citied peer-reviewed publication in the field.
Prof. Woo's Team Discovers Eco-Friendly Solid-Oxide Fuel Cell System
A KAIST research team led by Prof. Seong-Ihl Woo of the Department of Chemical & Biomolecular Engineering has found a method to use glycerol, a byproduct from the production of biodiesel, as fuel for solid oxide fuel cells (SOFC), university authorities said on Tuesday (Oct. 27). The research finding shows that glycerol can be an environmentally sustainable fuel when it is used for operating SOFCs with internal reforming, instead of hydrogen and methane. The finding was published in the Oct. 14, 2009 online edition of ChemSusChem, a sister journal of Angewandte Chemie, the world"s leading chemistry journal. Biodiesel is an attractive alternative energy source because of its low sulfur content and demand is growing worldwide as oil price soars. Bio-derived glycerol will not contribute to the greenhouse effect and has the potential to contribute to reducing global warming. Currently, glycereol is used as a raw material in the cosmetic, pharmacy, food, and tobacco industries. However, its supply exceeds its demand as the volume of biodiesel production increases. The production of 1 ton of biodiesel produces 0.1 ton of glycerol. Many researchers have investigated various routes for the consumption of surplus glycerol. The research is expected to contribute to sustainable growth by reducing the emissions of carbon dioxide and reusing generated carbon dioxide for the production of biomass. The new method enables manufacturers to use glycerol as a fuel for operating SOFC.
KAIST Secures Top Ranking of Korean Universities
KAIST won the No. 1 position for the second year in a row in the daily JoongAng Ilbo"s university rankings for 2009. Seoul National University took back the No. 2 spot, followed in order by POSTECH, Korea and Yonsei universities. The survey was conducted in the four categories, educational environment/finance, professors" research, general reputation/social advancement and globalization. KAIST scored 293 points out of possible 400 this year, while the second-ranking SNU and third-ranking POSTECH earned 234 and 226 points, respectively. The daily noted that KAIST particularly excelled in the category of educational environment/finance. It observed that donations to KAIST surged almost 100 times for the past three years since 2006 when President Suh took office. In specific rankings of universities by academic disciplines, SNU came in first overall. KAIST topped in the science and engineering field, while Korea University ranked first in liberal arts studies. This year, 88 four-year universities participated in the survey. The daily JoongAng Ilbo started its annual evaluation of Koran universities in 1994 to stimulate productive competition among institutions of higher learning and to provide objective standards for students and their parents to select schools for application. For more information, news.joins.com/article/391/3789391.html
KAIST Senior Wins Prizes at International Design Contests
Sung-Joon Kim, a senior at the Department of Industrial Design, KAIST, has recently won the highest prize at the iF Communication Design Award held in Hanover, Germany, university officials said on Monday (June 3). The prizewinning work entitled "1/2 PROJECT" introduces a donation system in which a customer buys a bottle of drink, for example, containing only a half of its price value and donate the remaining half of the value. The work which was created as part of the Samsung Design Membership was also awarded a silver prize at the International Design Excellence Awards (IDEA) of the United States. Award ceremonies of the two prizes are scheduled for in Muenchen in August and in Miami in September, respectively. "The design project is aimed at making donation a part of everyday life by teaming up with big-name beverage makers," said Kim. iF Communication Design Award and the IDEA are among the world"s three leading international design competitions. The other one is the Red Dot Design Award presented in Essen, Germany. Early this year, Kim, leading a team, presented a portable life saving equipment called "Rescue Stick" to the two competitions and won high honors.
Prof. Cho Identifies Dynamics of Signal Transportation System in Control of Cell Proliferation
KAIST, Jan. 22, 2009 -- A research team led by Prof. Kwang-Hyun Cho of the Department of Bio and Brain Engineering, KAIST, has identified a hidden mechanism of the dynamic behavior of signal transportation system involved in the control of cell proliferation, university authorities said. The finding is expected to provide a clue to appropriately controlling the pathway of ERK protein which is known to play a significant role in causing and spreading cancer. The research was featured as the cover paper of the latest online edition of the Journal of Cell Science. The Ras-Raf-MEK-ERK pathway (or ERK pathway) is an important signal transduction system involved in the control of cell proliferation, survival and differentiation. However, the dynamic regulation of the pathway by positive- and negative-feedback mechanism, in particular the functional role of Raf kinase inhibitor protein (RKIP) are still incompletely understood. RKIP is a physiological endogenous inhibitor of MEK phosphorylation by Raf kinases, but also participates in a positive-feedback loop in which ERK can inactivate RKIP. "We attempted to unearth the hidden dynamics of these feedback mechanisms and to identify the functional role of RKIP through combined efforts of biochemical experiments and computer simulations based on an experimentally validated mechanical model," Prof. Cho was quoted as saying.
KAIST Opens Cell Bench Research Center
KAIST opened a cell bench research center on the campus on Monday, Nov. 17, as a joint project with Samsung Electric Co. and Samsung Medical Center. On hand at the opening ceremony were about 100 persons from the three organizations, including KAIST President Nam-Pyo Suh, Samsung Electric"s Chief Technology Officer (CTO) Byung-Cheon Koh and Samsung Medical Center Vice President Hyo-Geun Lim. The newly-opened research center will be involved in the development of individually-tailored anti-cancer medicine using bio-inspired cell chips and technologies for clinical applications. Prof. Young-Ho Cho of the Department of Bio and Brain Engineering was named director of the research center. "Top-notch professionals from the electronic industry, academia and the medical community have gathered together to establish this research center. We expect the center will open a new path for the science and technology community and the industry to combine their strengths and develop innovative anti-cancer therapeutics," said KAIST President Nam-Pyo Suh at the opening ceremony. "The development of bio-cell chip technology represents a new challenge for the Samsung Electric which has focused on information technologies thus far. Through cooperation with KAIST and Samsung Medical Center, we expect to be able to develop a simple and efficient cure for cancer patients," commented Samsung Electric CTO Byung-Cheon Koh. The research center will be initially concentrating on the development of cell chips for lung cancer, one of the primary causes of death for Koreans.
President Nam-Pyo Suh Receives Lifetime Achievement Award from SPE
President Nam-Pyo Suh has been selected as a recipient of the Lifetime Achievement Award by the Society of Plastic Engineers (SPE). The SPE is the largest professional organization that promotes polymer-related R&D. The SPE announced that it recognizes President Suh’s many contributions to the field of polymer processing. President Suh established the first university/industry cooperative research program at MIT known as the MIT-Industry Polymer Processing Program, which became a model in establishing similar programs at many other universities by NSF. Among the many new materials, products and manufacturing processes invented by him are: Microcellular plastics, known as MuCell and used commercially worldwide, USM high pressure foam molding technology, electrostatic charge-decay NDE technique for polymeric materials, and foam/straight plastic lamination process (a major industrial product).
Researchers Find Mechanism of Tumor Suppressor Genes
By Kim Tae-gyu. Staff ReporterTHE Korea Times 02-06-2004 Korean scientists continue to break new ground in fighting cancer as domestic researchers examined the mechanism of a gene which can help detect and treat various sorts of cancer. Korea Advanced Institute of Science and Technology (KAIST) Prof. Lim Dae-sik on Thursday said his team uncovered the mechanism of RASSF1A (Ras Association Domain Family 1 A), or tumor suppressor genes, for the first time in the world. The gene was widely considered to play an important role in reducing the proliferation of cancer cells, but its exact function and processes have remained unknown up to now. It is the second cancer-related breakthrough by Koreans in a week after Korea Institute of Science and Technology (KIST) Prof. Chung Hesson unveiled the oral anti-cancer drug. ``Cancer results from the failed management of cell cycles due to things like radiation. After a two-year intensive study, we found out how RASSF1A governs the cell cycle,"" Lim said. Lim added cancer is caused by abnormal cells, which continue to grow and divide out of control unlike normal cells, which die over time. Cancer cells develop into malignant tumors, eventually inflicting damaging effect on the human body. As a result, a lack of the RASSF1A indicates a high possibility of cancer and injection of it into cells is believed to help cure the deadly disease, according to Lim. Dr. Song Min-sup, who took charge of the research, said the findings will especially pave the way for the detection and treatment of lung cancer. ``The dearth of RASSF1A was reported mostly in the case of lung cancer. The new findings will provide insight into the diagnosis and cure of lung cancer from its early stages,"" Song explained. Lung cancer is a very elusive disease because it doesn"t cause symptoms in its infancy. When symptoms do occur, usually it is too late. ``We expect commercial detection kits or drugs for lung cancer in around five years after pre-clinic experimentation and two-phase clinic trials,"" Song expected. Details of the study is available in the scientific journal Nature Cell Biology in its February edition. email@example.com
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