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High Resolution 3D Blood Vessel Endoscope System Developed
Professor Wangyeol Oh of KAIST’s Mechanical Engineering Department has succeeded in developing an optical imaging endoscope system that employs an imaging velocity, which is up to 3.5 times faster than the previous systems. Furthermore, he has utilized this endoscope to acquire the world’s first high-resolution 3D images of the insides of in vivo blood vessel. Professor Oh’s work is Korea’s first development of blood vessel endoscope system, possessing an imaging speed, resolution, imaging quality, and image-capture area. The system can also simultaneously perform a functional imaging, such as polarized imaging, which is advantageous for identifying the vulnerability of the blood vessel walls. The Endoscopic Optical Coherence Tomography (OCT) System provides the highest resolution that is used to diagnose cardiovascular diseases, represented mainly by myocardial infarction. However, the previous system was not fast enough to take images inside of the vessels, and therefore it was often impossible to accurately identify and analyze the vessel condition. To achieve an in vivo blood vessel optical imaging in clinical trials, the endoscope needed to be inserted, after which a clear liquid flows instantly, and pictures can be taken in only a few seconds. The KAIST research team proposed a solution for such problem by developing a high-speed, high-resolution optical tomographic imaging system, a flexible endoscope with a diameter of 0.8 mm, as well as a device that can scan the imaging light within the blood vessels at high speed. Then, these devices were combined to visualize the internal structure of the vessel wall. Using the developed system, the researchers were able to obtain high-resolution images of about 7 cm blood vessels of a rabbit’s aorta, which is similar size to human’s coronary arteries. The tomography scan took only 5.8 seconds, at a speed of 350 scans per second in all three directions with a resolution of 10~35㎛. If the images are taken every 200 ㎛, like the currently available commercial vascular imaging endoscopes, a 7cm length vessel can be imaged in only one second. Professor Wangyeol Oh said, “Our newly developed blood vessel endoscope system was tested by imaging a live animal’s blood vessels, which is similar to human blood vessels. The result was very successful.” “Collaborating closely with hospitals, we are preparing to produce the imaging of an animal’s coronary arteries, which is similar in size to the human heart,” commented Professor Oh on the future clinical application and commercialization of the endoscope system. He added, “After such procedures, the technique can be applied in clinical patients within a few years.” Professor Oh’s research was supported by the National Research Foundation of Korea and the Global Frontier Project by the Korean government. The research results were published in the 2014 January’s edition of Biomedical Optics Express. Figure 1: End portion of optical endoscope (upper left) Figure 2: High-speed optical scanning unit of the endoscope (top right) Figure 3: High-resolution images of the inside of in vivo animal blood vessels (in the direction of vascular circumference and length) Figure 4: High-resolution images of the inside of in vivo animal blood vessels (in the direction of the vein depth)
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.
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.
The output of terahertz waves enhanced by KAIST team
KAIST researchers have greatly improved the output of terahertz waves, the blue ocean of the optics world. This technology is expected to be applied to portable X-ray cameras, small bio-diagnostic systems, and in many other devices. Professor Ki-Hun Jeong"s research team from the Department of Bio and Brain Engineering used optical nano-antenna technology to increase the output of terahertz waves by three times. Terahertz waves are electromagnetic waves with frequencies between 100GHz to 30THz. They are produced when a femtosecond (10^-15 s) pulse laser is shone on a semiconductor substrate with photoconduction antennas, causing a photocurrent pulse of one picosecond (10^-12 s). Their long wavelengths, in comparison to visible light and infrared rays, give terahertz waves a high penetration power with less energy than X-rays, making them less harmful to humans. These qualities allow us to see through objects, just as X-rays do, but because terahertz waves absorb certain frequencies, we can detect hidden explosives or drugs, which was not possible with X-rays. We can even identify fake drugs. Furthermore, using the spectral information, we can analyze a material"s innate qualities without chemical processing, making it possible to identify skin diseases without harming the body. However, the output was not sufficient to be used in biosensors and other applications. Prof. Jeong"s team added optical nano-antennas, made from gold nano-rods, in between the photoconduction antennas and optimized the structure. This resulted in nanoplasmonic resonance in the photoconduction substrate, increasing the degree of integration of the photocurrent pulse and resulting in a three times larger output. Hence, it is not only possible to see through objects more clearly, but it is also possible to analyze components without a biopsy. Professor Jeong explained, "This technology, coupled with the miniaturization of terahertz devices, can be applied to endoscopes to detect early epithelial cancer" and that he will focus on creating and commercializing these biosensor systems. This research was published in the March issue of the international nanotechnology journal ACS Nano and was funded by the Korea Evaluation Institute of Industrial Technology and the National Research Foundation of Korea. Figure: Mimetic diagram of a THz generator with nano-antennas
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