Cell
-
Hidden Mechanism for the Suppression of Colon Cancer Identified
Published in Cell Reports : cells at the risk of causing colorectal cancer due to genetic mutation are discharged outside the colon tissue
Korean researchers have successfully identified the cancer inhibitory mechanism of the colon tissue. The discovery of the inherent defense mechanism of the colon tissues is expected to provide understanding of the cause of colorectal cancer.
The research was led by Kwang-Hyun Cho, a professor of Bio and Brain Engineering at KAIST (corresponding author) and participated by Dr. Jehun Song (the first author), as well as Dr. Owen Sansom, David Huels, and Rachel Ridgway from the Beatson Institute for Cancer Research in the UK and Dr. Walter Kolch from Conway Institute in Ireland.
The research was funded by the Ministry of Science, ICT and Future Planning and the National Research Foundation of Korea, and its results were published in the 28th March online edition of Cell Reports under the title of “The APC network regulates the removal of mutated cells from colonic crypts.”
The organism can repair damaged tissues by itself, but genetic mutations, which may cause cancer, can occur in the process of cell division s for the repair. The rapid cell division s and toxic substances from the digestive process cause a problem especially in colon crypt that has a high probability for genetic mutation.
The research team was able to find out that the colon tissues prevent cancer by rapidly discharging carcinogenic cells with genetic mutations from the colon crypt durin ga frequent tissue repair process.
This defense mechanism, which inhibits abnormal cell division s by reducing the time mutated cells reside in the crypt, is inherent in the colon.
Extensive mathematical simulation results show that the mutated cells with enhanced Wnt signaling acquire increased adhesion in comparison to the normal cells, which therefore move rapidly toward the upper part of the crypt and are discharged more easily.
If beta-catenine, the key factor in Wnt signal transduction pathway, is not degraded due to genetic mutation, the accumulated beta-catenine activates cell proliferation and increases cell adhesion. The special environment of crypt tissue and the tendency of the cells with similar adhesion to aggregate will therefore discharge the mutated cell, hence maintaining the tissue homeostasis.
In vivo experiment with a mouse model confirms the simulation results that, in the case of abnormal crypt, the cells with high proliferation in fact move slower.
Professor Cho said, “This research has identified that multicellular organism is exquisitely designed to maintain the tissue homeostasis despite abnormal cell mutation. This also proves the systems biology research, which is a convergence of information technology and bio-technology , can discover hidden mechanisms behind complex biological phenomena.”
Crypt: Epithelium, consisting of approximately 2,000 cells, forms a colon surface in the shape of a cave.
Wnt Signaling: A signal transduction pathway involved in the proliferation and differentiation of cells that are particularly important for the embryonic development and management of adult tissue homeostasis.
2014.04.17 View 12151 -
Professor Sang-Min received an award for scholar of the year from the KAISTian of the Year 2013
KAIST nominates a “Scholar of the Year” each year and presents the award to the recipient at a New Year’s opening ceremony. For the year 2013, Professor Sang-Min Bae of the Industrial Design Department at KAIST was named “KAIST Scholar of 2013” and received the award on January 2, 2014.
Professor Bae has been recognized for his design achievement in 2013: D’Light, a kinetic lighting that employs a transformable lampshade using flexible honeycomb structure, became one of the finalists in the living room and bedroom category of the International Design Excellence Award 2013 and was selected one of the best 100 for the 2013 Good Design Award. Users can easily change the shape and light intensity of the lamp by simply pivoting the lampshade with its small handle.
Professor Bae has also actively pursued his own philanthrophic projects through design: he has given the profits from the sales of his designs including D’Light directly toward a scholarship for needy children.
The Scholar of the Year award is presented to a faculty member or researcher at KAIST who has contributed to the advancement of science and technology such as publication of articles with influential research outcomes, invention of breakthrough technology, implementation of outstanding research projects, and improvement of public life. Professor Bae is the 13 th winner of the KAIST award.
The Korea Times, a leading English language newspaper in Korea, published an article on this award. For the article, please visit http://www.koreatimes.co.kr/www/news/people/2014/01/178_149117.html .
2014.01.09 View 10646 -
Kinetic Lighting, Dlight, Dominates World Renowned Design Awards
Professor Sang-Min Bae
“D’light,” a lamp that transforms its lampshade shape, developed by a team led by KAIST Department of Industrial Design’s Professor Sang-Min Bae, won Japan’s Good Design Awards on October the 2nd, soon after winning the internationally renowned 2013 International Design Excellence Awards (IDEA) in August.
IDEA, sponsored by the Industrial Design Society of America (IDSA) and BusinessWeek, awards the best work from over 6,000 exhibits from 50 countries. Japan’s Good Design Awards, founded by the Japan Institute of Design Promotion (JDP) in 1957, is the most prestigious and one of the World’s four major design awards.
“D’light” combines “donative” and “light.” Its meaning originates from the meaning of “delight” which means “giving great joy.” The shape and the brightness of the lamp can be transformed by turning the end of the heart-shaped lampshade. The team states that the lamp carries a figurative meaning of generous hearts lighting the neglected of the world by designing the lamp to be the brightest when it takes the shape of a heart. D’light developed as the 5th product of “the Nanum” project that started in 2006. Professor Bae first participated in the project in developing the 2nd product, “Cross Cube” in 2007. The he designed and launched the environmentally friendly humidifier “Lovepot” in 2008 and interactive tumbler “Hearty” in 2009.
The “Nanum” project aims to develop innovative products for charity to create a humane social circulatory system. The project, led by the international relief and development organisation, World Vision and KAIST’s ID+IM laboratory run by Professor Bae, donates all profits to educate the children of low-income families. The project raised a total of 1.7 billion Korean won from 2007 this year to provide scholarships to 240 children in need.
Professor Bae’s team has undertaken seed and “Nanum” projects with the theme of philanthropy design helping people in need by creating innovative designs. The project has produced four excellent and authentic products which received 44 world renowned design awards.
Professor Bae said, “’The Nanum’ project consists of planning, designing, producing and selling for charity and donates all profit to children in need through education and scholarship.” He continued, “The consumers can purchase products that are aesthetically pleasing and convenient as well as gaining an opportunity to donate to children in need.”
Figure1 Kinetic lighting D’light
Figure 2. Characteristics of “Nanum” D’light
The shape of the lampshade can be transformed. The lamp sheds the brightest light when it takes the shape of a heart, hence showing the figurative meaning of brightening the neglected parts of the world with generous hearts.
Figure 3. Detailed Images of D’light
2013.11.11 View 10022 -
A powerful strategy for developing microbial cell factories by employing synthetic small RNAs
The current systems for the production of chemicals, fuels and materials heavily rely on the use of fossil resources. Due to the increasing concerns on climate change and other environmental problems, however, there has been much interest in developing biorefineries for the production of such chemicals, fuels and materials from renewable resources. For the biorefineries to be competitive with the traditional fossil resource-based refineries, development of high performance microorganisms is the most important as it will affect the overall economics of the process most significantly. Metabolic engineering, which can be defined as purposeful modification of cellular metabolic and regulatory networks with an aim to improve the production of a desired product, has been successfully employed to improve the performance of the cell. However, it is not trivial to engineer the cellular metabolism and regulatory circuits in the cell due to their high complexity.
In metabolic engineering, it is important to find the genes that need to be amplified and attenuated in order to increase the product formation rate while minimizing the production of undesirable byproducts. Gene knock-out experiments are often performed to delete those metabolic fluxes that will consequently result in the increase of the desired product formation. However, gene knock-out experiments require much effort and time to perform, and are difficult to do for a large number of genes. Furthermore, the gene knock-out experiments performed in one strain cannot be transferred to another organism and thus the whole experimental process has to be repeated. This is a big problem in developing a high performance microbial cell factory because it is required to find the best platform strain among many different strains. Therefore, researchers have been eager to develop a strategy that allows rapid identification of multiple genes to be attenuated in multiple strains at the same time.
A Korean research team led by Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering from the Korea Advanced Institute of Science and Technology (KAIST) reported the development of a strategy for efficiently developing microbial cell factories by employing synthetic small RNAs (sRNAs). They first reported the development of such system in Nature Biotechnology last February. This strategy of employing synthetic sRNAs in metabolic engineering has been receiving great interest worldwide as it allows easy, rapid, high-throughput, tunable, and un-doable knock-down of multiple genes in multiple strains at the same time. The research team published a paper online on August 8 as a cover page (September issue) in Nature Protocols, describing the detailed strategy and protocol to employ synthetic sRNAs for metabolic engineering.
In this paper, researchers described the detailed step-by-step protocol for synthetic sRNA-based gene expression control, including the sRNA design principles. Tailor-made synthetic sRNAs can be easily manipulated by using conventional gene cloning method. The use of synthetic sRNAs for gene expression regulation provides several advantages such as portability, conditionality, and tunability in high-throughput experiments. Plasmid-based synthetic sRNA expression system does not leave any scar on the chromosome, and can be easily transferred to many other host strains to be examined. Thus, the construction of libraries and examination of different host strains are much easier than the conventional hard-coded gene manipulation systems. Also, the expression of genes can be conditionally repressed by controlling the production of synthetic sRNAs. Synthetic sRNAs possessing different repression efficiencies make it possible to finely tune the gene expression levels as well. Furthermore, synthetic sRNAs allow knock-down of the expression of essential genes, which was not possible by conventional gene knock-out experiments.
Synthetic sRNAs can be utilized for diverse experiments where gene expression regulation is needed. One of promising applications is high-throughput screening of the target genes to be manipulated and multiple strains simultaneously to enhance the production of chemicals and materials of interest. Such simultaneous optimization of gene targets and strains has been one of the big challenges in metabolic engineering. Another application is to fine tune the expression of the screened genes for flux optimization, which would enhance chemical production further by balancing the flux between biomass formation and target chemical production. Synthetic sRNAs can also be applied to finely regulating genetic interactions in a circuit or network, which is essential in synthetic biology. Once a sRNA scaffold-harboring plasmid is constructed, tailor-made, synthetic sRNAs can be made within 3-4 days, followed by the desired application experiments.
Dr. Eytan Zlotorynski, an editor at Nature Protocols, said "This paper describes the detailed protocol for the design and applications of synthetic sRNA. The method, which has many advantages, is likely to become common practice, and prove useful for metabolic engineering and synthetic biology studies."
This paper published in Nature Protocols will be useful for all researchers in academia and industry who are interested in the use of synthetic sRNAs for fundamental and applied biological and biotechnological studies.
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012-C1AAA001-2012M1A2A2026556) and the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) of the Ministry of Science, ICT and Future Planning through the National Research Foundation of Korea.
2013.10.31 View 9804
-
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 18937 -
Top Ten Ways Biotechnology Could Improve Our Everyday Life
The Global Agenda Council on Biotechnology, one of the global networks under the World Economic Forum, which is composed of the world’s leading experts in the field of biotechnology, announced on February 25, 2013 that the council has indentified “ten most important biotechnologies” that could help meet rapidly growing demand for energy, food, nutrition, and health. These new technologies, the council said, also have the potential to increase productivity and create new jobs.
“The technologies selected by the members of the Global Agenda Council on Biotechnology represent almost all types of biotechnology.Utilization of waste, personalized medicine,and ocean agricultureare examples of the challenges where biotechnology can offer solutions,”said Sang Yup Lee, Chair of the Global Agenda Council on Biotechnology and Distinguished Professor in the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST). He also added that “the members of the council concluded that regulatory certainty, public perception, and investment are the key enablers for the growth of biotechnology.”
These ideas will be further explored during “Biotechnology Week” at the World Economic Forum’s Blog (http://wef.ch/blog) from Monday, 25 February, 2013. The full list follows below:
Bio-based sustainable production of chemicals, energy, fuels and materials
Through the last century, human activity has depleted approximately half of the world’s reserves of fossil hydrocarbons. These reserves, which took over 600 million years to accumulate, are non-renewable and their extraction, refining and use contribute significantly to human emissions of greenhouse gases and the warming of our planet. In order to sustain human development going forward, a carbon-neutral alternative must be implemented. The key promising technology is biological synthesis; that is, bio-based production of chemicals, fuels and materials from plants that can be re-grown.
Engineering sustainable food production
The continuing increase in our numbers and affluence are posing growing challenges to the ability of humanity to produce adequate food (as well as feed, and now fuel). Although controversial, modern genetic modification of crops has supported growth in agricultural productivity. In 2011, 16.7 million farmers grew biotechnology-developed crops on almost 400 million acres in 29 countries, 19 of which were developing countries. Properly managed, such crops have the potential to lower both pesticide use and tilling which erodes soil.
Sea-water based bio-processes
Over 70% of the earth surface is covered by seawater, and it is the most abundant water source available on the planet. But we are yet to discover the full potential of it. For example with halliophic bacteria capable of growing in the seawater can be engineered to grow faster and produce useful products including chemicals, fuels and polymeric materials. Ocean agriculture is also a promising technology. It is based on the photosynthetic biomass from the oceans, like macroalgae and microalgae.
Non-resource draining zero waste bio-processing
The sustainable goal of zero waste may become a reality with biotechnology. Waste streams can be processed at bio-refineries and turned into valuable chemicals and fuels, thereby closing the loop of production with no net waste. Advances in biotechnology are now allowing lower cost, less draining inputs to be used, including methane, and waste heat. These advances are simplifying waste streams with the potential to reduce toxicity as well as support their use in other processes, moving society progressively closer to the sustainable goal of zero waste.
Using carbon dioxide as a raw material
Biotechnology is poised to contribute solutions to mitigate the growing threat of rising CO2 levels. Recent advances are rapidly increasing our understanding of how living organisms consume and use CO2. By harnessing the power of these natural biological systems, scientists are engineering a new wave of approaches to convert waste CO2 and C1 molecules into energy, fuels, chemicals, and new materials.
Regenerative medicine
Regenerative medicine has become increasingly important due to both increased longevity and treatment of injury. Tissue engineering based on various bio-materials has been developed to speed up the regenerative medicine. Recently, stem cells, especially the induced pluripotent stem cells (iPS), have provided another great opportunity for regenerative medicine. Combination of tissue engineering and stem cell (including iPS) technologies will allow replacements of damaged or old human organs with functional ones in the near future.
Rapid and precise development and manufacturing of medicine and vaccines
A global pandemic remains one of the most real and serious threats to humanity. Biotechnology has the potential to rapidly identify biological threats, develop and manufacture potential cures. Leading edge biotechnology is now offering the potential to rapidly produce therapeutics and vaccines against virtually any target. These technologies, including messenger therapeutics, targeted immunotherapies, conjugated nanoparticles, and structure-based engineering, have already produced candidates with substantial potential to improve human health globally.
Accurate, fast, cheap, and personalized diagnostics and prognostics
Identification of better targets and combining nanotechnology and information technology it will be possible to develop rapid, accurate, personalized and inexpensive diagnostics and prognostics systems.
Bio-tech improvements to soil and water
Arable land and fresh water are two of the most important, yet limited, resources on earth. Abuse and mis-appropriation have threatened these resources, as the demand on them has increased. Advances in biotechnology have already yielded technologies that can restore the vitality and viability of these resources. A new generation of technologies: bio-remediation, bio-regeneration and bio-augmentation are being developed, offering the potential to not only further restore these resources, but also augment their potential.
Advanced healthcare through genome sequencing
It took more than 13 years and $1.5 billion to sequence the first human genome and today we can sequence a complete human genome in a single day for less than $1,000. When we analyze the roughly 3 billion base pairs in such a sequence we find that we differ from each other in several million of these base pairs. In the vast majority of cases these difference do not cause any issues but in rare cases they cause disease, or susceptibility to disease. Medical research and practice will increasingly be driven by our understanding of such genetic variations together with their phenotypic consequences.
2013.03.19 View 12059
-
Op-Ed by Professor David Helfman: Global Science and Education in Korea for the 21st Century
Professor David Helfman from the Department of Biological Sciences and Graduate School of Nanoscience and Technology contributed an op-ed, “Global Science and Education in Korea for the 21st Century, to the Korea Herald on February 20, 2013. For the article, please click the link below:
http://www.koreaherald.com/view.php?ud=20130220000623.
2013.02.26 View 10530
-
Professor Shin In Shik First in Asia to receive Excellent Dissertation Award from IEEE RTSS
The research team lead by Professor Shin In Shik (Department of Computer Science) received the Excellent Dissertation Awardy in the IEEE RTSS out of 157 dissertations.
It is the first time a Professor under an institute in the Asia region received the Award in the RTSS field during its 33 year history.
Professor Shin had already received an Excellent Dissertation Award as a Ph.D. candidate at the University of Pennsylvania. Thus Professor Shin became the first and only scientist to receive the Award twice.
Professor Shin has successfully defined the scheduling method of the multicore processor which was regarded as the problem in the field of RTSS for the past decade.
Professor Shin has suggested new criteria for sorting real time tasks in parallel thereby suggesting a new scheduling method that surpasses current scheduling methods. The results are anticipated to provide new perspectives in the field of RTSS using multicore processors.
2013.01.22 View 8518
-
Op-Ed by Prof. David Helfman: Global Science and Education in the 21st Century
Professor David Helfman from the Department of Biological Sciences and Graduate School of Nanoscience and Technology(https://sites.google.com/site/cellsignalinglaboratory/home) recently wrote an Op-Ed in the January 2013 issue of Journal of Happy Scientists and Engineers that ispublished by the Ministry of Science, Education and Technology, the Republic of Korea. In the article entitled “Global Science and Education in the 21st Century,” Professor Helfman addressed three important issues in science and education, which will have a great impact for the development of world-leading universities in Korea. For the article, please see the attachment.
2013.01.22 View 12228
-
Professor Bae Sang Min Wins Multiple Prestigious Design Awards
Summer is perfect for many outdoor activities, but it is also the season for mosquitoes, an annoying pest that makes outdoor experiences unpleasant and sometimes even dangerous. An easy-to-use and environmentally-friendly spray, “Sound Spray” (http://idsa.org/soundspray-self-generating-non-toxic-ultrasonic-anti-mosquito-spray), which repels mosquitoes by setting off ultrasonic waves, has been developed by a research team at KAIST. The spray produces sounds similar to those of mosquitoes’ natural predators.
Sound Spray made the list of finalists in the category of "Social Impact Design" from the 2012 International Design Excellence Awards (IDEA). The IDEA is one of the most renowned design competitions in the world, which has been held annually by the Industrial Designers Society of America (IDSA).
Inside Sound Spray is a battery that generates electricity when a user shakes the spray bottle. Electrical energy produced by the battery creates an ultrasonic sound that mosquitoes dislike, thereby discouraging their contact with human skin. Professor Sangmin Bae from the Department of Industrial Design at KAIST explains,
“In regions such as Africa or Southeast Asia, mosquitoes are still posing a big threat to public health. Unlike Freon-based, disposable insect repellents on the market, Sound Spray is eco-friendly, easy to carry around, reusable, and affordable. I plan to commercialize and distribute it to nations in Africa or Southeast Asia to help them combat against malaria, an infectious disease that patients contract through mosquito bites.”
Professor Bae also received another award from the 2012 IDEA in the area of Commercial and Industrial Products: a bronze medal for a milling machine, the Namsun Milling Machine (http://www.idsa.org/namsunnew-innovative-milling-machine-design). The machine has large windows on each side of its main body that display a transparent workflow so that users easily understand the machine’s operation status. Curved lines are actively used for the exterior design of the machine to create a more friendly work environment.
In addition to the 2012 IDEA, Professor Bae has participated in other major international design awards, including the Red Dot Award, the If Design Award Japan, and the Good Design Award, from which his research team has received a total of 41 prizes.
Professor Bae initiated a campaign in 2005 called “Philanthropy Design,” through which he has donated many of his designs to help people in need. For more on his research, please visit http://www.coroflot.com/frame29/Portfolio1.
2012.07.26 View 12295 -
Systems biology demystifies the resistance mechanism of targeted cancer medication
Korean researchers have found the fundamental resistance mechanism of the MEK inhibitor, a recently highlighted chemotherapy method, laying the foundation for future research on overcoming cancer drug resistance and improving cancer survival rates. This research is meaningful because it was conducted through systems biology, a fusion of IT and biotechnology.
The research was conducted by Professor Gwang hyun Cho’s team from the Department of Biology at KAIST and was supported by the Ministry of Education, Science and Technology and the National Research Foundation of Korea.
The research was published as the cover paper for the June edition of the Journal of Molecular Cell Biology (Title: The cross regulation between ERK and PI3K signaling pathways determines the tumoricidal efficacy of MEK inhibitor).
Targeted anticancer medication targets certain molecules in the signaling pathway of the tumor cell and not only has fewer side effects than pre-existing anticancer medication, but also has high clinical efficacy. The technology also allows the creation of personalized medication and has been widely praised by scientists worldwide.
However, resistances to the targeted medication have often been found before or during the clinical stage, eventually causing the medications to fail to reach the drug development stage. Moreover, even if the drug is effective, the survival rate is low and the redevelopment rate is high.
An active pathway in most tumor cells is the ERK (Extracellular signal-regulated kinases) signaling pathway. This pathway is especially important in the development of skin cancer or thyroid cancer, which are developed by the mutation of the BRAF gene inside the path. In these cases, the MEK (Extracellular signal-regulated kinases) inhibitor is an effective treatment because it targets the pathway itself. However, the built-up resistance to the inhibitor commonly leads to the redevelopment of cancer.
Professor Cho’s research team used large scale computer simulations to analyze the fundamental resistance mechanism of the MEK inhibitor and used molecular cell biological experiments as well as bio-imaging* techniques to verify the results.
* Bio-imaging: Checking biological phenomena at the cellular and molecular levels using imagery
The research team used different mutational variables, which revealed that the use of the MEK inhibitor reduced the transmission of the ERK signal but led to the activation of another signaling pathway (the PI3K signaling pathway), reducing the effectiveness of the medication. Professor Cho’s team also found that this response originated from the complex interaction between the signaling matter as well as the feedback network structure, suggesting that the mix of the MEK inhibitor with other drugs could improve the effects of the targeted anticancer medication.
Professor Cho stated that this research was the first of its kind to examine the drug resistivity against the MEK inhibitor at the systematic dimension and showed how the effects of drugs on the signaling pathways of cells could be predicted using computer simulation. It also showed how basic research on signaling networks can be applied to clinical drug use, successfully suggesting a new research platform on overcoming resistance to targeting medication using its fundamental mechanism.
2012.07.06 View 11789
-
Successful Development of Excavation System of Biomarkers containing Protein Decomposition Control Enzyme Information
A Korean team of researchers successfully developed a biomarker excavation system named E3Net that excavates biomarkers containing information of the enzymes that control the decomposition of proteins. The development of the system paved the possibility of development of new high quality biomarkers.
*Biomarker: Molecular information of unique patterns derived from genes and proteins that allow the monitoring of physical changes from genetic or environmental causes.
Professor Lee Kwan Soo’s team (Department of Biological Sciences) composed of Doctorate candidate Han Young Woong, Lee Ho Dong Ph.D. and Professor Park Jong Chul published a dissertation in the April edition of Molecular and Cellular Proteomics. (Dissertation Title: A system for exploring E3-mediated regulatory networks of cellular functions).
Professor Lee’s team compiled all available information of the enzyme that controls protein decomposition (E3 enzyme) and successfully compiled the inter-substrate network by extracting information from 20,000 biology related data base dissertations. The result was the development of the E3Net system that analyzes the related cell function and disease.
Cells have a system that produces, destroys, and recycles proteins in response to the ever changing environmental conditions. Error in these processes leads to disease.
Therefore finding the relationship between E3 enzymes that control the decomposition of proteins and the substrates will allow disease curing and prevention to become much easier. E3 enzyme is responsible for 80% of the protein decomposition and is therefore predicted to be related to various diseases.
However the information on E3 enzyme and inter-substrate behavior are spread out among numerous dissertations and data bases which prevented methodological analysis of the role of the related cells and characteristics of the disease itself.
Professor Lee’s team was successful in creating the E3Net that compiled 2,201 pieces of E3 substrate information, 4,896 pieces of substrate information, and 1,671 pieces of inter-substrate relationship information. This compilation allows for the systematic analysis of cells and diseases.
The newly created network is 10 times larger than the existing network and is the first case where it is possible to accurately find the cell function and related diseases.
It is anticipated that the use of the E3Net will allow the excavation of new biomarkers for the development of personalized drug systems.
The research team applied the E3Net to find tens of new candidate biomarkers related to the major modern diseases like diabetes and cancer.
2012.05.30 View 12925