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Mechanism in regulation of cancer-related key enzyme, ATM, for DNA damage and repair revealed
Professor Kwang-Wook Choi
A research team led by Professor Kwang-Wook Choi and Dr. Seong-Tae Hong from the Department of Biological Sciences at KAIST has successfully investigated the operational mechanism of the protein Ataxia Telangiectasia Mutated (ATM), an essential protein to the function of a crucial key enzyme that repairs the damaged DNA which stores biometric information. The results were published on December 19th Nature Communications online edition.
All organisms, including humans, constantly strive to protect the information within their DNA from damages posed by a number of factors, such as carbonized materials in our daily food intake, radioactive materials such as radon emitting from the cement of buildings or ultraviolet of the sunlight, which could be a trigger for cancer.
In order to keep the DNA information safe, the organisms are always carrying out complex and sophisticated DNA repair work, which involves the crucial DNA damage repair protein ATM. Consequently, a faulty ATM leads to higher risks of cancer.
Until now, academia predicted that the Translationally Controlled Tumor Protein (TCTP) will play an important role in regulating the function of ATM. However, since most of main research regarding TCTP has only been conducted in cultured cells, it was unable to identify exactly what mechanisms TCTP employs to control ATM.
The KAIST research team identified that TCTP can combine with ATM or increase the enzymatic activity of ATM. In addition, Drosophilia, one of the most widely used model organisms for molecular genetics, has been used to identify that TCTP and ATM play a very important role in repairing the DNA damaged by radiation. This information has allowed the researchers to establish TCTP’s essential function in maintaining the DNA information in cell cultures and even in higher organisms, and to provide specific and important clues to the regulation of ATM by TCTP.
Professor Kwang-Wook Choi said, “Our research is a good example that basic research using Drosophilia can make important contributions to understanding the process of diseases, such as cancer, and to developing adequate treatment.”
The research has been funded by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea.
Figure 1. When the amount of TCTP protein is reduced, cells of the Drosophila's eye are abnormally deformed by radiation. Scale bars = 200mm
Figure 2. When the amount of TCTP protein is reduced, the chromosomes of Drosophilia are easily broken by radiation. Scale bars = 10 mm.
Figure 3. When gene expressions of TCTP and ATM are reduced, large defects occur in the normal development of the eye. (Left: normal Drosophilia's eye, right: development-deficient eye)
Figure 4. ATM marks the position of the broken DNA, with TCTP helping to facilitate this reaction. DNA (blue line) within the cell nucleus is coiled around the histone protein (green cylinder). When DNA is broken, ATM protein attaches a phosphate group (P). Multiple DNA repair protein recognizes the phosphate as a signal that requires repair and gathers at the site.
2014.01.07 View 13749 -
First International Conference on Science and Technology for Society
KAIST co-organized the 2013 International Conference on Science and Technology for Society which was held on November 28 at the Grace Hall in Seoul EL-Tower. More than 300 people, including members of the Global Social Technology Advisory Board, domestic social technology experts, private companies, government officials, private citizens, and students joined the conference to discuss the roles and responsibilities of science and technology for society.
R&D policies and technologies for solving social issues were introduced, and discussions were held on desirable directions for technological development.
The first speaker, Yasushi Watanabe, Director of RISTEX (Research Institute of Science and Technology for Society) in Japan, introduced the importance of science and technology for society under the title “Change of R&D Paradigm for Society.”
Robert Wimmer, GrAT (Center for Appropriate Technology), Vienna University of Technology in Austria, presented “Need-oriented Design & Solutions for Development.” Kiyoaki Murakami, MRI, Japan, presented “Introduction of Platinum Vision” and Robert Ries, University of Florida, U.S.A., presented “Evaluating the Social Impacts of the Built Environment Using Life Cycle Assessment.”
Case studies on social enterprises and presentations on R&D for solving social problems were introduced by ICISTS (International Conference for the Integration of Science, Technology and Society), which is a student group at KAIST, National Research Foundation of Korea (NRF), Korea Institute of Machinery and Materials (KIMM), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Korea Institute of Industrial Technology (KITECH), Electronics and Telecommunication Research Institute (ETRI), and Korea Research Institute of Chemical Technology (KRICT).The conference was hosted by the Ministry of Science, ICT, and Future Planning and co-organized by NRF, KIMM, KRIBB, KITECH, ETRI and KRICT.
2013.12.11 View 11955 -
Final Results of the 2013 Intelligent SoC Robot War
KAIST hosted the 2013 Intelligent System on Chip (SoC) Robot War, the largest intelligent robot contest in Korea, from Oct. 24 to 27 at KINTEX in Ilsan, Korea.
Professor Hoi-Jun Yoo, from the Department of Electrical Engineering at KAIST, started the contest in 2003 to promote Taekwondo, a Korean martial art, and Korean semiconductor technology to the world.
The winning team was awarded an honorary certificate from Kookiwon, the world headquarters of Taekwondo.
Competitions were held in two different categories: Taekwon Robot and Huro Competition.
In the Taekwon Robot contest, intelligent robots loaded with cameras and semiconductor chips competed in Taekwondo skills.
In the Huro Competition, intelligent humanoid robots competed in detecting and passing huddles.
Approximately 550 participants from 107 groups applied for the 12th Intelligent SoC Robot War and 22 groups were selected for the final tournament. The best teams in each category received an award from the president and prime minister of the Republic of Korea, respectively.
Professor Yoo, the operating chair of the contest, said, “The contest was organized to introduce both technology and tradition by presenting robots with Taekwondo skills. The experiences from this contest could be the foundation for future robot technology and the growth engine for the next generation.”
Professor Yoo is a leading researcher in the field of object recognition chip, and his papers were often presented at the International Solid State Circuits Conference.Details of the contest can be found at http://www.socrobotwar.org.
2013.11.15 View 9045 -
Nanowire Made of Diverse Materials May Become Marketable
- Technology to commercialize nanowire developed after 2 years of industrial-academic joint research -
- 2 million strands of 50nm-width, 20 cm-length nanowire mass producible in 2 hours –
A South Korean joint industrial-academic research team has developed the technology to put forward the commercialization of nanowire that is only a few nanometers wide. It is expected to be applied in various fields such as semiconductors, high performance sensors, and biodevices.
In cooperation with LG Innotek and the National Nanofab center, Professor Jun-Bo Yoon, from KAIST Department of Electrical Engineering, developed the technology to mass produce nanowire at any length with various materials. The research results are published on the online edition of Nano Letters on July 30th.
Nanowire has a long linear structure with its width at 100 nanometers at maximum. It is a multifunctional material that has yet undiscovered thermal, electric, and mechanical properties. Nanowire is highly acclaimed as a cutting-edge material with unique nano-level properties that can be applied in semiconductors, energy, biodevices, and optic devices.
Previously, nanowires had an extremely low synthesis rate that required three or four days to grow few millimeters. It was therefore difficult to produce the desired products using nanowires. Moreover, nanowires needed to be evenly arranged for practical application, but the traditional technology required complex post-treatment, not to mention the arrangement was not immaculate.
The research team applied semiconductor process instead of chemical synthesis to resolve these issues. The team first formed a pattern greater that of the target frequency by using a photo-engraving process on a silicon wafer board whose diameter was 20 centimeters, then repeatedly reduced the frequency to produce 100 nm ultrafine linear grid pattern. Based on this pattern, the research team applied the sputtering process to mass-produce nanowires in perfect shapes of 50 nm width and 20 cm maximum length.
The new technology requires neither a lengthy synthesis process nor post-cleaning to attain a perfectly aligned state. Thus, academic and industrial circles consider the technology has high possibilities for commercialization.
“The significance is in resolving the issues in traditional technology, such as low productivity, long manufacturing time, restrictions in material synthesis, and nanowire alignment,” commented Professor Yoon on this research. “Nanowires have not been widely applied in the industry, but this technology will bring forward the commercialization of high performance semiconductors, optic devices, and biodevices that make use of nanowires.”
2013.10.18 View 9765 -
Therapy developed to induce Angiogenesis of Retina
- Junyeop Lee, Graduate School of Medical Sciences and Engineering
- Research results expected to be applied for treatment of diabetic retinopathy
A major clue to treatment of retinovascular disease, which causes blindness, has been found. The key to protection of the retinal nerve is the angiogenic protein that promotes healthy retinal vessel growth around the retina, which usually does not receive blood supply readily. This research offers a beginning to the possible improvement of therapy for diabetic retinopathy1 and retinopathy of prematurity2. Also important to the research is the fact that the ophthalmology specialist researcher, currently undergoing professional training, provided the results.
KAIST Graduate School of Medical Sciences and Engineering’s Junyeop Lee is the opthalmology specialist, who carried out the research under supervision by academic advisers Gyuyeong Go and Wookjun Yoo. The Ministry of Science, ICT and Future Planning as well as the National Research Foundation of Korea have funded his research. The research results have been published as a cover paper on ‘Science Translational Medicine’ on 18th August. This journal is a sister publication of Science, which is prestigious in the field of translational medicine that ties the basic science with clinical medicine. (Thesis title: Angiopoietin-1 Guides Directional Angiogenesis Through Integrin αvβ5 Signaling for Recovery of Ischemic Retinopathy)
The traditional treatment of diabetic retinopathy includes laser photocoagulation to destroy the retinal tissues or antibody therapeutics, which prevents vessel proliferation and blood leaking. The advantage of antibody therapeutics3 is that it retains the retinal nerves, however, it is not the fundamental solution but merely a temporary one, which requires repeated treatments.
The research team identified that Angiopoietin-14 protein, known as essential for growth and stabilization of vessels, also plays an important role in retinal vessel growth. The protein protects the retinal nerves, as well as provides improvement for retinal ischemia5 that is the root cause of vision loss due to retinal hemorrhages. It is expected to become a key to finding fundamental treatment method – by providing sufficient blood supply to the retina, thereby preserving the retinal nerve functions.
The results show that administration of Angiopoietin-1 to retinopathy mouse model promotes growth of healthy vessel growth, further preventing abnormal vessel growth, retinal hemorrhage and vision loss due to retinal ischemia.
Junyeop Lee said, “This research has identified that Angiopoietin-1 is an important factor in retinal vessel generation and stabilization. The paradigm will shift from traditional treatment method, which prevents vessel growth, to a new method that generates healthy vessels and strengthens vessel functions.”
1 Diabetic retinopathy: This retinovascular disease is a diabetic complication caused by insufficient blood supply. It is the major causes of blindness in adults.
2 Retinopathy of prematurity: The retinal vascular disease that occurs in premature infants with incomplete retinal vascular development. It is also the most common cause of blindness in children.
3 Antibody Therapeutics: Antibody developed to selectively inhibit abnormal blood vessel growth and leakage. Typical antibody therapeutics is Avastin and Lucentis, which hinder vascular endothelial growth factor (VEGF).
4 Angiopoietin-1: A critical growth factor that induces the production of healthy blood vessels and maintains the stability of the created vessel.
5 Retinal ischemia: State of ailment where retinal tissue blood supply is not sufficient.
Figure 1. Retinopathy mouse models show that, in comparison to the control group, the VEGF-Trap treatment and Angiopoietin-1 (Ang1) treatment groups significantly suppresses the pathological vascular proliferation. In addition, the Ang 1 group show vessel growth toward the central avascular area (region of retinal ischemia), which is not observed in VEGF-Trap treatment.
Figure 2. Reduced retinal ischemia, retinal bleeding and blood vessel normalization by Angiopoietin-1. Retinal ischemic region (arrow) and retinal bleeding significantly reduced in the Angiopoietin-1 (Ang1) treatment model in comparison to control group (left). The newly generated vessels in Ang 1 model are structurally supported by perivascular cells as normal retinal vessels do (right).
2013.10.12 View 11912 -
Short Wavelength, Ultra-High Speed Quantum Light Source based on Quantum Dot Developed
Professor Yong Hoon, Cho (Department of Physics) and his research team synthesized an obelisk nanostructure and successfully formed a single semiconductor quantum exhibiting high reliability to realize an ultra-high speed, highly efficient, release of quantum dots.
The result of the research effort was published in the July 5th online edition of Scientific Reports published by Nature.
Semiconductor Quantum Dots restrict electrons within a cubic boundary of few nanometers thereby exhibiting similar properties to an atom with discontinuous energy levels. Exploitation of this characteristic makes possible the development of quantum light source, critical for next generation quantum information communication and quantum encryption.
High operational temperatures, stability, rapid photon release, electric current capability, and other advantages are reasons why semiconductor quantum dots are regarded as next generation core technology.
However conventional, spontaneously formed quantum dots are densely packed in a planar structure rendering the analysis of a single quantum dot difficult and result in the poor efficiency of photon release. In addition, the internal electromagnetic effect which is caused by inter-planar stress results in low internal quantum efficiency due to the difficulty in electron-hole recombination.
Professor Cho’s research team synthesized an obelisk shaped nanostructure using nitrides that emit short wavelengths of light. The activation layer was grown on the tip of the nanostructure and the team succeeded in placing a single quantum dot on the nano-tip. The team was therefore able to confirm the ultra-high speed single photon characteristics which occur at low energy levels.
Use of unique nanostructures makes synthesis of single atomic structures without processes like patterning while enabling the release of light emitted by the quantum dot.
Using this unique method the team showed the increase in internal quantum efficiency. The electromagnetic forces apparent in thin films no longer affects the quantum dot greatly due to the obelisk structure’s reduced inter planar stress.
The newly developed quantum light source emits visible light (400nm range) and not the conventional infrared light. This characteristic makes possible it use in communication in free space and enables use of highly efficient, visible range photon detector.
Professor Cho commented that “the developed method makes quantum dot growth much easier making single photon synthesis much faster to contribute to the development of practical quantum light source.” And that “the characteristics of the obelisk nanostructure enable the easy detachment from and attachment to other substrates enabling its use in producing single chip quantum light source.”
The research was conducted under the supervision of Professor Cho. The researchers werey Jae Hyung, Kim (first author) and Yong Ho, Ko (second author), both Ph.D. candidates at KAIST. The Ministry of Science, ICT and Future Planning, the National Research Foundation, and WCU Program provided support to the research effort.
2013.08.23 View 8744 -
Thinking Out of the Box: KAIST Silicon Valley Innovation Platform
KAIST established a liaison office in San Jose, California, to support the entrepreneurship of KAIST graduates, students, and faculty who aspire to transform their innovative ideas into business.
The office, KAIST Silicon Valley Innovation Platform (SVIP), is located within the Korea Trade-Investment Promotion Agency (KOTRA) IT Center on North First Street in San Jose.
SVIP collects information and analyzes trends on emerging technologies; provides various educational programs on entrepreneurship and technology translation; offers opportunities to prospective entrepreneurs to engage with industry and research and government organizations; and assists Korean startups in accessing the US and North American market.
President Steve Kang attended the opening ceremony of the office on June 14th and encouraged KAIST alumni living in the US to share their ideas and technology innovations and transform them into business opportunities.
For more information, please contact Professor Soung-Hie Kim (seekim@business.kaist.ac.kr) from the Graduate School of Information and Media Management, KAIST.
2013.07.04 View 9037 -
Neurotransmitter protein structure and operation principle identified
Professor Tae-Young Yoon
- Real-time measurement of structural change of bio-membrane fusion protein
- A new clue to degenerative brain diseases research
KAIST Physics Department’s Professor Tae-Young Yoon has successfully identified the hidden structure and operation mechanism of the SNARE protein, which has a central role in transporting neurotransmitters between neurons, using magnetic nanotweezers. SNARE protein’s cell membrane fusion function is closely related to degenerative brain diseases or neurological disorders such as Alzheimer’s. Hence, this research may provide a clue to the disease’s prevention and treatment.
Neurotransmission occurs when vesicles containing neurotransmitters fuse with cell membranes in neuron synapses. The SNARE protein is a cell-membrane fusion protein with a core role of releasing neurotransmitters. The academia speculated the SNARE protein would regulate the exchange of neurotransmitters, but its precise function and structure has been unknown. Professor Yoon’s research team developed an experimental technique using nanotweezers to measure physical changes to nanometer level by pulling and releasing each protein with force of 1 pN (piconewton). The research identified the existence of hidden SNARE protein"s intermediate structure. The process of withstanding and maintaining repulsive forces between bio-membranes in the hidden intermediate structure of SNARE to regulate the exchange of neurotransmitters has also been identified.
Professor Yoon’s research team developed an experimental technique using magnetic nanotweezers to measure physical changes of proteins to nanometer level by pulling and releasing each protein with force of 1 pN. The research identified the existence of hidden SNARE protein"s intermediate structure and its formation. The process of withstanding and maintaining repulsive forces between bio-membranes in the hidden intermediate structure of SNARE to regulate the exchange of neurotransmitters has also been discovered.
Professor Yoon said, “Ground breaking research results have been produced. A simple experimental technique of applying the smallest possible forces to proteins (with tweezers) to see their hidden structure and formation process can produce the same result as real observation has been developed.” He continued, “This technique will be very important in researching biological object with physical experimental technique. It will be a vital foundation to consilient research of different academia in the future.”
This research was a joint project of Physics Department’s Professor Tae-Young Yoon, KAIST, and Biomedical Engineering Institute’s Professor Yeon-Kyun Shin at KIST. KAIST Physics Department’s Professor Yong-Hoon Cho, Ph.D. candidate Do-Yong Lee and KIAS Computational Sciences Department’s Professor Chang-Bong Hyun participated. The research was published on Nature Communications on April 16th.
a) Neurotransmission occurs when vesicles containing neurotransmitters fuse with cell membranes in neuron synapses. A SNARE protein is a cell-membrane fusion protein with a core role of releasing neurotransmitters.
b) A schematic diagram using magnetic nanotweezers to measure protein structure changes on molecular level. The nanotweezers exert an exquisite pull and release of each protein with a force of 1 pN to measure physical changes to nanometer level in real-time to observe the hidden intermediate structure and operation principles of bio-membrane fusion protein.
2013.05.25 View 9640 -
Award Winning Portable Sound Camera Design
- A member of KAIST’s faculty has won the “Red Dot Design Award,” one of three of the most prestigious design competitions in the world, for the portable sound camera.
KAIST’s Industrial Design Professor Suk-Hyung Bae’s portable sound camera design, made by SM Instruments and Hyundai, has received a “Red Dot Design Award: Product Design,” one of the most prestigious design competitions in the world.
If you are a driver, you must have experienced unexplained noises in your car. Most industrial products, including cars, may produce abnormal noises caused by an error in design or worn-out machinery. However, it is difficult to identify the exact location of the sound with ears alone.
This is where the sound camera comes in. Just as thermal detector cameras show the distribution of temperature, sound cameras use a microphone arrangement to express the distribution of sound and to find the location of the sound. However, existing sound cameras are not only too big and heavy, their assembly and installation are complex and must be fixed on a tripod. These limitations made it impossible to measure noises from small areas or the base of cars.
The newly developed product is an all-in-one system resolving the inconvenience of assembling the microphone before taking measurements. Moreover, the handle in the middle is ergonomically designed so users can balance its weight with one hand. The two handles on the sides work as a support and enable the user to hold the camera in various ways.
At the award ceremony, Professor Suk-Hyung Bae commented, “The effective combination of cutting edge technology and design components has been recognized.” He also said, “It shows the competency of the KAIST’s Department of Industrial Design, which has a high understanding of science and technology.”
On the other hand, SM Instruments is a sound vibration specialist company which got its start from KAIST’s Technology Business Incubation Centre in 2006 and earned its independence by gaining proprietary technology in only two years. SM Instruments is contributing to developing national sound and vibration technology through relentless change and innovation. ;
Figure 1: Red Dot Design Award winning the portable sound camera, SeeSV-S205
Figure 2: Identifying the location of the noise using the portable sound camera
Figure 3: The image showing the sound distribution using the portable sound camera
2013.04.09 View 20424 -
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 19417 -
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 12011 -
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 12373