biology
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Professor Kwang-Hyun Cho publishes Encyclopaedia of Systems Biology
Professor Kwang-Hyun Cho
KAIST Biological and Brain Engineering Department’s Professor Kwang-Hyun Cho edited the Encyclopaedia of Systems Biology with three scholars, all experts of Systems Biology in England, Germany and the United States. It is rare that a Korean scientist edits a world renowned academic science encyclopaedia.
The Encyclopaedia, published by the New York office of Springer Verlag, was a grand international project five years in the making by 28 editors and 391 scientists with expertise in Systems Biology from around the world. The Encyclopaedia compiles various research areas of Systems Biology, the new academic paradigm of the 21st century through the integration of IT and BT, comprehensively on 3,000 pages in 4 four volumes.
Professor Kwang-Hyun Cho, who led this international project, majored in electrical engineering and pioneered the field of Systems Biology, the integrated study of biological sciences and engineering, as a new integrated field of IT since the 1990s. The professor has achieved various innovative research results since then. Recently he has investigated “kernel,” an evolutionary core structure in complex biological networks and developed a new cancer treatment through the state space analysis of the molecular network of cancer cells. His work was published in Science Signalling, a sister journal of Science, as a cover story several times, and contributed to foundational research as well as commercialisation of the integrated fields of IT and BT.
2013.08.27 View 8753 -
The new era of personalized cancer diagnosis and treatment
Professor Tae-Young Yoon
- Succeeded in observing carcinogenic protein at the molecular level
- “Paved the way to customized cancer treatment through accurate analysis of carcinogenic protein”
The joint KAIST research team of Professor Tae Young Yoon of the Department of Physics and Professor Won Do Huh of the Department of Biological Sciences have developed the technology to monitor characteristics of carcinogenic protein in cancer tissue – for the first time in the world.
The technology makes it possible to analyse the mechanism of cancer development through a small amount of carcinogenic protein from a cancer patient. Therefore, a personalised approach to diagnosis and treatment using the knowledge of the specific mechanism of cancer development in the patient may be possible in the future.
Until recently, modern medicine could only speculate on the cause of cancer through statistics. Although developed countries, such as the United States, are known to use a large sequencing technology that analyses the patient’s DNA, identification of the interactions between proteins responsible for causing cancer remained an unanswered question for a long time in medicine.
Firstly, Professor Yoon’s research team has developed a fluorescent microscope that can observe even a single molecule. Then, the “Immunoprecipitation method”, a technology to extract a specific protein exploiting the high affinity between antigens and antibodies was developed. Using this technology and the microscope, “Real-Time Single Molecule co-Immunoprecipitation Method” was created. In this way, the team succeeded in observing the interactions between carcinogenic and other proteins at a molecular level, in real time.
To validate the developed technology, the team investigated Ras, a carcinogenic protein; its mutation statistically is known to cause around 30% of cancers.
The experimental results confirmed that 30-50% of Ras protein was expressed in mouse tumour and human cancer cells. In normal cells, less than 5% of Ras protein was expressed. Thus, the experiment showed that unusual increase in activation of Ras protein induces cancer.
The increase in the ratio of active Ras protein can be inferred from existing research data but the measurement of specific numerical data has never been done before.
The team suggested a new molecular level diagnosis technique of identifying the progress of cancer in patients through measuring the percentage of activated carcinogenic protein in cancer tissue.
Professor Yoon Tae-young said, “This newly developed technology does not require a separate procedure of protein expression or refining, hence the existing proteins in real biological tissues or cancer cells can be observed directly.” He also said, “Since carcinogenic protein can be analyzed accurately, it has opened up the path to customized cancer treatment in the future.”
“Since the observation is possible on a molecular level, the technology confers the advantage that researchers can carry out various examinations on a small sample of the cancer patient.” He added, “The clinical trial will start in December 2012 and in a few years customized cancer diagnosis and treatment will be possible.”
Meanwhile, the research has been published in Nature Communications (February 19). Many researchers from various fields have participated, regardless of the differences in their speciality, and successfully produced interdisciplinary research. Professor Tae Young Yoon of the Department of Physics and Professors Dae Sik Lim and Won Do Huh of Biological Sciences at KAIST, and Professor Chang Bong Hyun of Computational Science of KIAS contributed to developing the technique.
Figure 1: Schematic diagram of observed interactions at the molecular level in real time using fluorescent microscope. The carcinogenic protein from a mouse tumour is fixed on the microchip, and its molecular characteristics are observed live.
Figure 2: Molecular interaction data using a molecular level fluorescent microscope. A signal in the form of spike is shown when two proteins combine. This is monitored live using an Electron Multiplying Charge Coupled Device (EMCCD). It shows signal results in bright dots.
An organism has an immune system as a defence mechanism to foreign intruders. The immune system is activated when unwanted pathogens or foreign protein are in the body. Antibodies form in recognition of the specific antigen to protect itself. Organisms evolved to form antibodies with high specificity to a certain antigen. Antibodies only react to its complementary antigens. The field of molecular biology uses the affinity between antigens and antibodies to extract specific proteins; a technology called immunoprecipitation. Even in a mixture of many proteins, the protein sought can be extracted using antibodies. Thus immunoprecipitation is widely used to detect pathogens or to extract specific proteins.
Technology co-IP is a well-known example that uses immunoprecipitation. The research on interactions between proteins uses co-IP in general. The basis of fixing the antigen on the antibody to extract antigen protein is the same as immunoprecipitation. Then, researchers inject and observe its reaction with the partner protein to observe the interactions and precipitate the antibodies. If the reaction occurs, the partner protein will be found with the antibodies in the precipitations. If not, then the partner protein will not be found. This shows that the two proteins interact.
However, the traditional co-IP can be used to infer the interactions between the two proteins although the information of the dynamics on how the reaction occurs is lost. To overcome these shortcomings, the Real-Time Single Molecule co-IP Method enables observation on individual protein level in real time. Therefore, the significance of the new technique is in making observation of interactions more direct and quantitative.
Additional Figure 1: Comparison between Conventional co-IP and Real-Time Single Molecule co-IP
2013.04.01 View 17146 -
Ligand Recognition Mechanism of Protein Identified
Professor Hak-Sung Kim
-“Solved the 50 year old mystery of how protein recognises and binds to ligands”
- Exciting potential for understanding life phenomena and the further development of highly effective therapeutic agent development
KAIST’s Biological Science Department’s Professor Hak-Sung Kim, working in collaboration with Professor Sung-Chul Hong of Department of Physics, Seoul National University, has identified the mechanism of how the protein recognizes and binds to ligands within the human body.
The research findings were published in the online edition of Nature Chemical Biology (March 18), which is the most prestigious journal in the field of life science.
Since the research identified the mechanism, of which protein recognises and binds to ligands, it will take an essential role in understanding complex life phenomenon by understanding regulatory function of protein.
Also, ligand recognition of proteins is closely related to the cause of various diseases. Therefore the research team hopes to contribute to the development of highly effective treatments.
Ligands, well-known examples include nucleic acid and proteins, form the structure of an organism or are essential constituents with special functions such as information signalling.
In particular, the most important role of protein is recognising and binding to a particular ligand and hence regulating and maintaining life phenomena. The abnormal occurrence of an error in recognition of ligands may lead to various diseases.
The research team focused on the repetition of change in protein structure from the most stable “open form” to a relatively unstable “partially closed form”.
Professor Kim’s team analysed the change in protein structure when binding to a ligand on a molecular level in real time to explain the ligand recognition mechanism.
The research findings showed that ligands prefer the most stable protein structure. The team was the first in the world to identify that ligands alter protein structure to the most stable, the lowest energy level, when it binds to the protein.
In addition, the team found that ligands bind to unstable partially-closed forms to change protein structure.
The existing models to explain ligand recognition mechanism of protein are “Induced Custom Model”, which involves change in protein structure in binding to ligands, and the “Structure Selection Model”, which argues that ligands select and recognise only the best protein structure out of many. The academic world considers that the team’s research findings have perfectly proved the models through experiments for the first time in the world.
Professor Kim explained, “In the presence of ligands, there exists a phenomenon where the speed of altering protein structure is changed. This phenomenon is analysed on a molecular level to prove ligand recognition mechanism of protein for the first time”. He also said, “The 50-year old mystery, that existed only as a hypothesis on biology textbooks and was thought never to be solved, has been confirmed through experiments for the first time.”
Figure 1: Proteins, with open and partially open form, recognising and binding to ligands.
Figure 2: Ligands temporarily bind to a stable protein structure, open form, which changes into the most stable structure, closed form. In addition, binding to partially closed form also changes protein structure to closed form.
2013.04.01 View 10345 -
High Efficiency Bio-butanol production technology developed
KAIST and Korean Company cooperative research team has developed the technology that increases the productivity of bio-butanol to equal that of bio-ethanol and decreases the cost of production.
Professor Lee Sang Yeop (Department of Biological-Chemical Engineering) collaborated with GS Caltex and BioFuelChem Ltd. to develop a bio-butanol production process using the system metabolism engineering method that increased the productivity and decreased the production cost.
Bio-butanol is being widely regarded as the environmentally friendly next generation energy source that surpasses bio-ethanol.
The energy density of bio-butanol is 29.9MJ (mega Joule) per Liter, 48% larger than bio-ethanol (19.6MJ) and comparable to gasoline (32MJ). Bio-butanol is advantageous in that it can be processed from inedible biomass and is therefore unrelated to food crises.
Especially because bio-butanol shows similar characteristics especially in its octane rating, enthalpy of vaporization, and air-fuel ratio, it can be used in a gasoline engine.
However barriers such as difficulty in gene manipulation of producer bacterium and insufficient information prevented the mass production of bio-butanol.
Professor Lee’s team applied the system metabolism engineering method that he had invented to shift the focus to the production pathway of bio-butanol and made a new metabolism model.
In the new model the bio-butanol production pathway is divided into the hot channel and the cold channel.
The research team focused on improving the efficiency of the hot channel and succeeded in improving the product yield of 49% (compared to theoretical yield) to 87%.
The team furthered their research and developed a live bio-butanol collection and removal system with GS Caltex. The collaboration succeeded in producing 585g of butanol using 1.8kg of glucose at a rate of 1.3g per hour, boasting world’s highest concentration, productivity, and rate and improving productivity of fermentation by three fold and decreasing costs by 30%.
The result of the research was published in world renowned ‘mBio’ microbiology journal.
2012.12.21 View 8531 -
Liver Damage Mechanism of Hepatitis C Proven
KAIST researchers found mechanics behind a Hepatitis C virus, thereby taking a step closer to the development of a cure for Hepatitis C.
Professor Choi Chul Hui (Department of Biological and Brain Engineering) and Professor Shin Eui Chul (Graduate School of Medical Sciences) proved, for the first time in the world, the mechanism behind liver damage of a patient with Hepatitis C.
It is anticipated that this discovery will allow for the development of a Hepatitis C cure that has no side effects and little Liver damage.
Hepatitis C is an immune response of the body to the Hepatitis C virus and causes liver irritation.
Around 170million people are infected with Hepatitis C worldwide including 1% of the Korean population. Once infected, most cases turn into chronic cases and may lead to liver cancer.
However it was impossible to infect Hepatitis C within a test tube cell environment until 2005 and up till then Chimpanzees were used to study the virus which proved to be a huge barrier to research.
The research team used cells infected with Hepatitis C virus and found out that the virus works by increasing the destruction of cells by the TNF-a protein responsible for the cell’s immune response.
In addition the protein structure of the virus that causes this reaction was successfully found.
Conventionally the Hepatitis C medication focused on the suppressing the growth of the virus and therefore had many side effects.
The experimental results allow new medication aimed at suppressing the actual mechanism of liver damage to be discovered.
The result was selected as the cover dissertation of the September Edition of the Hepatolog magazine.
2012.09.11 View 11454
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Production of chemicals without petroleum
Systems metabolic engineering of microorganisms allows efficient production of natural and non-natural chemicals from renewable non-food biomass
In our everyday life, we use gasoline, diesel, plastics, rubbers, and numerous chemicals that are derived from fossil oil through petrochemical refinery processes. However, this is not sustainable due to the limited nature of fossil resources. Furthermore, our world is facing problems associated with climate change and other environmental problems due to the increasing use of fossil resources. One solution to address above problems is the use of renewable non-food biomass for the production of chemicals, fuels and materials through biorefineries. Microorganisms are used as biocatalysts for converting biomass to the products of interest. However, when microorganisms are isolated from nature, their efficiencies of producing our desired chemicals and materials are rather low. Metabolic engineering is thus performed to improve cellular characteristics to desired levels. Over the last decade, much advances have been made in systems biology that allows system-wide characterization of cellular networks, both qualitatively and quantitatively, followed by whole-cell level engineering based on these findings. Furthermore, rapid advances in synthetic biology allow design and synthesis of fine controlled metabolic and gene regulatory circuits. The strategies and methods of systems biology and synthetic biology are rapidly integrated with metabolic engineering, thus resulting in "systems metabolic engineering".
In the paper published online in Nature Chemical Biology on May 17, Professor Sang Yup Lee and his colleagues at the Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea present new general strategies of systems metabolic engineering for developing microorganisms for the production of natural and non-natural chemicals from renewable biomass. They first classified the chemicals to be produced into four categories based on whether they have thus far been identified to exist in nature (natural vs. nonnatural) and whether they can be produced by inherent pathways of microorganisms (inherent, noninherent, or created): natural-inherent, natural-noninherent, non-natural-noninherent, and non-natural-created ones. General strategies for systems metabolic engineering of microorganisms for the production of these chemicals using various tools and methods based on omics, genome-scale metabolic modeling and simulation, evolutionary engineering, synthetic biology are suggested with relevant examples. For the production of non-natural chemicals, strategies for the construction of synthetic metabolic pathways are also suggested. Having collected diverse tools and methods for systems metabolic engineering, authors also suggest how to use them and their possible limitations.
Professor Sang Yup Lee said "It is expected that increasing number of chemicals and materials will be produced through biorefineries. We are now equipped with new strategies for developing microbial strains that can produce our desired products at very high efficiencies, thus allowing cost competitiveness to those produced by petrochemical refineries."
Editor of Nature Chemical Biology, Dr. Catherine Goodman, said "It is exciting to see how quickly science is progressing in this field – ideas that used to be science fiction are taking shape in research labs and biorefineries. The article by Professor Lee and his colleagues not only highlights the most advanced techniques and strategies available, but offers critical advice to progress the field as a whole."
The works of Professor Lee have been supported by the Advanced Biomass Center and Intelligent Synthetic Biology Center of Global Frontier Program from the Korean Ministry of Education, Science and Technology through National Research Foundation.
Contact: Dr. Sang Yup Lee, Distinguished Professor and Dean, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930)
2012.05.23 View 11683
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10 Technolgies to Change the World in 2012: The Future Technology Global Agenda Council
The Future Technology Global Agenda Council which is under the World Economy Forum and which KAIST’s biochemical engineering department’s Prof. Sang Yeob Lee is the head of, chose the 10 new technologies that will change the world in year 2012.
The ten technologies include: IT, synthetic biology and metabolic engineering, Green Revolution 2.0, material construction nanotechnology, systematic biology and the simulation technology of biological systems, the technology to use CO2 as a natural resource, wireless power transmission technology, high density energy power system, personalized medical/nutritional/disease preventing system, and new education technology.
The technologies were chosen on the basis of the opinions various science, industry, and government specialists and is deemed to have high potential to change the world in the near future.
The Future Technology Global Agenda Council will choose ten new technologies yearly starting this year in order to solve the problems the world now faces.
The informatics systems that was ranked 1st place, sifts only the data necessary for decision making out of the overflowing amount of data. Much interest has been spurred at the Davos forum.
The synthetic biology and metabolic engineering chosen is expected to play an important role in creating new medicines and producing chemical substances and materials from reusable resources.
Biomass has also been chosen as one of the top ten most important technologies as it was seen to be necessary to lead the second Green Revolution in order to stably provide food for the increasing population and to create bio refineries.
Nanomaterials structured at the molecular level are expected to help us solve problems regarding energy, food, and resources.
Systematic biology and computer modeling is gaining importance in availing humans to construct efficient remedies, materials, and processes while causing minimum effects on the environment, resource reserves, and other people.
The technology to convert CO2, which is considered a problem all over the world, into a useful resource is also gaining the spotlight
Together with such technologies, wireless power transmission technology, high density energy power system, personalized medical/nutritional/disease preventing system, and new education technology are also considered the top ten technologies to change the world.
Prof. Lee said, “Many new discoveries are being made due to the accelerating rate of technological advancements. Many of the technologies that the council has found are sustainable and important for the construction of our future.”
2012.04.04 View 10264
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Future of Petrochemical Industry: The Age of Bio-Refineries
The concept of bio-refinery is based on using biomass from seaweeds and non-edible plant sources to produce various materials.
Bio-refineries has been looked into with increasing interest in modern times due to the advent of global warming (and the subsequent changes in the atmosphere) and the exhaustion of natural resources.
However past 20 years of research in metabolic engineering had a crucial limitation; the need to improve the efficiency of the microorganisms that actually go about converting biomass into biochemical materials.
In order to compensate for the inefficiency, Professor Lee Sang Yeop combined systems biology, composite biology, evolutionary engineering to form ‘systems metabolic engineering’.
This allows combining various data to explain the organism’s state in a multi-dimensional scope and respond accordingly by controlling the metabolism.
The result of the experiment is set as the cover dissertation of ‘Trends in Biotechnology’ magazine’s August edition.
2011.07.28 View 10771
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New Bio-Clock gene and its function found
The Ministry of Education, Science and Technology announced that a Korean research team has found a new gene responsible for maintaining the bio-clock (twenty-four) and its mechanism.
Twnety-four was led by Professor Choi Joon Ho and Dr. Lee Jong Bin of KAIST (department of Biology) and was a joint operation with Professor Ravi Allada and Dr.Lim Jeong Hoon of Northwestern University (department of neurobiology) and the result was published in ‘Nature’ magazine.
The research team experimented with transformed small fruit flies for 4 years and found that there was an undiscovered gene that deals with the bio rhythm in the brain which they named ‘twenty-four’.
The understanding with genes prior to twenty-four was that these genes regulate biorhythm in the transcription phase (DNA to mRNA). Twenty-four operates in the step after transcription when the ribosome creates proteins. Especially twenty-four has a great effect on the ‘period protein’ which acts as a sub-atomic clock that regulates the rhythm and life of each cell.
The experiment was innovational in that it was able to scientifically prove the function of the protein produced by the gene.
The result is expected to help solve the problems associated with sleep disorders, jetlags, eating rhythms, bio rhythms, etc.
The name twenty-four was the fact that a day, a cycle, is 24 hours long and the gene’s serial numbers CG4857 adds up to twenty four.
2011.02.23 View 10898
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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 14584
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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 11593 -
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 14612