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New Nanoparticle Drug Combination For Atherosclerosis
Physicochemical cargo-switching nanoparticles (CSNP) designed by KAIST can help significantly reduce cholesterol and macrophage foam cells in arteries, which are the two main triggers for atherosclerotic plaque and inflammation. The CSNP-based combination drug delivery therapy was proved to exert cholesterol-lowering, anti-inflammatory, and anti-proliferative functions of two common medications for treating and preventing atherosclerosis that are cyclodextrin and statin. Professor Ji-Ho Park and Dr. Heegon Kim from KAIST’s Department of Bio and Brain Engineering said their study has shown great potential for future applications with reduced side effects. Atherosclerosis is a chronic inflammatory vascular disease that is characterized by the accumulation of cholesterol and cholesterol-loaded macrophage foam cells in the intima. When this atherosclerotic plaque clogs and narrows the artery walls, they restrict blood flow and cause various cardiovascular conditions such as heart attacks and strokes. Heart attacks and strokes are the world’s first and fifth causes of death respectively. Oral statin administration has been used in clinics as a standard care for atherosclerosis, which is prescribed to lower blood cholesterol and inhibit its accumulation within the plaque. Although statins can effectively prevent the progression of plaque growth, they have only shown modest efficacy in eliminating the already-established plaque. Therefore, patients are required to take statin drugs for the rest of their lives and will always carry the risk of plaque ruptures that can trigger a blood clot. To address these issues, Professor Park and Dr. Kim exploited another antiatherogenic agent called cyclodextrin. In their paper published in the Journal of Controlled Release on March 10, Professor Park and Dr. Kim reported that the polymeric formulation of cyclodextrin with a diameter of approximately 10 nanometers(nm) can accumulate within the atherosclerotic plaque 14 times more and effectively reduce the plaque even at lower doses, compared to cyclodextrin in a non-polymer structure. Moreover, although cyclodextrin is known to have a cytotoxic effect on hair cells in the cochlea, which can lead to hearing loss, cyclodextrin polymers developed by Professor Park’s research group exhibited a varying biodistribution profile and did not have this side effect. In the follow-up study reported in ACS Nano on April 28, the researchers exploited both cyclodextrin and statin and form the cyclodextrin-statin self-assembly drug complex, based on previous findings that each drug can exert local anti-atherosclerosis effect within the plaque. The complex formation processes were optimized to obtain homogeneous and stable nanoparticles with a diameter of about 100 nm for systematic injection. The therapeutic synergy of cyclodextrin and statin could reportedly enhance plaque-targeted drug delivery and anti-inflammation. Cyclodextrin led to the regression of cholesterol in the established plaque, and the statins were shown to inhibit the proliferation of macrophage foam cells. The study suggested that combination therapy is required to resolve the complex inflammatory cholesterol-rich microenvironment within the plaque. Professor Park said, “While nanomedicine has been mainly developed for the treatment of cancers, our studies show that nanomedicine can also play a significant role in treating and preventing atherosclerosis, which causes various cardiovascular diseases that are the leading causes of death worldwide.” This work was supported by KAIST and the National Research Foundation (NRF) of Korea. Publications: 1. Heegon Kim, Junhee Han, and Ji-Ho Park. (2020) ‘Cyclodextrin polymer improves atherosclerosis therapy and reduces ototoxicity’ Journal of Controlled Release. Volume 319. Page 77-86. Available online at https://doi.org/10.1016/j.jconrel.2019.12.021 2. Kim, H., et al. (2020) ‘Affinity-Driven Design of Cargo-Switching Nanoparticles to Leverage a Cholesterol-Rich Microenvironment for Atherosclerosis Therapy’ ACS Nano. Available online at https://doi.org/10.1021/acsnano.9b08216 Profile: Ji-Ho Park, Ph.D. Associate Professor email@example.com http://openwetware.org/wiki/Park_Lab Biomaterials Engineering Laboratory (BEL) Department of Bio and Brain Engineering (BIOENG) Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Heegon Kim, Ph.D. Postdoctoral Researcher firstname.lastname@example.org BEL, BIOENG, KAIST (END)
Unravelling Complex Brain Networks with Automated 3-D Neural Mapping
-Automated 3-D brain imaging data analysis technology offers more reliable and standardized analysis of the spatial organization of complex neural circuits.- KAIST researchers developed a new algorithm for brain imaging data analysis that enables the precise and quantitative mapping of complex neural circuits onto a standardized 3-D reference atlas. Brain imaging data analysis is indispensable in the studies of neuroscience. However, analysis of obtained brain imaging data has been heavily dependent on manual processing, which cannot guarantee the accuracy, consistency, and reliability of the results. Conventional brain imaging data analysis typically begins with finding a 2-D brain atlas image that is visually similar to the experimentally obtained brain image. Then, the region-of-interest (ROI) of the atlas image is matched manually with the obtained image, and the number of labeled neurons in the ROI is counted. Such a visual matching process between experimentally obtained brain images and 2-D brain atlas images has been one of the major sources of error in brain imaging data analysis, as the process is highly subjective, sample-specific, and susceptible to human error. Manual analysis processes for brain images are also laborious, and thus studying the complete 3-D neuronal organization on a whole-brain scale is a formidable task. To address these issues, a KAIST research team led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering developed new brain imaging data analysis software named 'AMaSiNe (Automated 3-D Mapping of Single Neurons)', and introduced the algorithm in the May 26 issue of Cell Reports. AMaSiNe automatically detects the positions of single neurons from multiple brain images, and accurately maps all the data onto a common standard 3-D reference space. The algorithm allows the direct comparison of brain data from different animals by automatically matching similar features from the images, and computing the image similarity score. This feature-based quantitative image-to-image comparison technology improves the accuracy, consistency, and reliability of analysis results using only a small number of brain slice image samples, and helps standardize brain imaging data analyses. Unlike other existing brain imaging data analysis methods, AMaSiNe can also automatically find the alignment conditions from misaligned and distorted brain images, and draw an accurate ROI, without any cumbersome manual validation process. AMaSiNe has been further proved to produce consistent results with brain slice images stained utilizing various methods including DAPI, Nissl, and autofluorescence. The two co-lead authors of this study, Jun Ho Song and Woochul Choi, exploited these benefits of AMaSiNe to investigate the topographic organization of neurons that project to the primary visual area (VISp) in various ROIs, such as the dorsal lateral geniculate nucleus (LGd), which could hardly be addressed without proper calibration and standardization of the brain slice image samples. In collaboration with Professor Seung-Hee Lee's group of the Department of Biological Science, the researchers successfully observed the 3-D topographic neural projections to the VISp from LGd, and also demonstrated that these projections could not be observed when the slicing angle was not properly corrected by AMaSiNe. The results suggest that the precise correction of a slicing angle is essential for the investigation of complex and important brain structures. AMaSiNe is widely applicable in the studies of various brain regions and other experimental conditions. For example, in the research team’s previous study jointly conducted with Professor Yang Dan’s group at UC Berkeley, the algorithm enabled the accurate analysis of the neuronal subsets in the substantia nigra and their projections to the whole brain. Their findings were published in Science on January 24. AMaSiNe is of great interest to many neuroscientists in Korea and abroad, and is being actively used by a number of other research groups at KAIST, MIT, Harvard, Caltech, and UC San Diego. Professor Paik said, “Our new algorithm allows the spatial organization of complex neural circuits to be found in a standardized 3-D reference atlas on a whole-brain scale. This will bring brain imaging data analysis to a new level.” He continued, “More in-depth insights for understanding the function of brain circuits can be achieved by facilitating more reliable and standardized analysis of the spatial organization of neural circuits in various regions of the brain.” This work was supported by KAIST and the National Research Foundation of Korea (NRF). Figure and Image Credit: Professor Se-Bum Paik, KAIST Figure and Image Usage Restrictions: News organizations may use or redistribute these figures and images, with proper attribution, as part of news coverage of this paper only. Publication: Song, J. H., et al. (2020). Precise Mapping of Single Neurons by Calibrated 3D Reconstruction of Brain Slices Reveals Topographic Projection in Mouse Visual Cortex. Cell Reports. Volume 31, 107682. Available online at https://doi.org/10.1016/j.celrep.2020.107682 Profile: Se-Bum Paik Assistant Professor email@example.com http://vs.kaist.ac.kr/ VSNN Laboratory Department of Bio and Brain Engineering Program of Brain and Cognitive Engineering http://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea (END)
Professor Sue-Hyun Lee Listed Among WEF 2020 Young Scientists
Professor Sue-Hyun Lee from the Department of Bio and Brain Engineering joined the World Economic Forum (WEF)’s Young Scientists Community on May 26. The class of 2020 comprises 25 leading researchers from 14 countries across the world who are at the forefront of scientific problem-solving and social change. Professor Lee was the only Korean on this year’s roster. The WEF created the Young Scientists Community in 2008 to engage leaders from the public and private sectors with science and the role it plays in society. The WEF selects rising-star academics, 40 and under, from various fields every year, and helps them become stronger ambassadors for science, especially in tackling pressing global challenges including cybersecurity, climate change, poverty, and pandemics. Professor Lee is researching how memories are encoded, recalled, and updated, and how emotional processes affect human memory, in order to ultimately direct the development of therapeutic methods to treat mental disorders. She has made significant contributions to resolving ongoing debates over the maintenance and changes of memory traces in the brain. In recognition of her research excellence, leadership, and commitment to serving society, the President and the Dean of the College of Engineering at KAIST nominated Professor Lee to the WEF’s Class of 2020 Young Scientists Selection Committee. The Committee also acknowledged Professor Lee’s achievements and potential for expanding the boundaries of knowledge and practical applications of science, and accepted her into the Community. During her three-year membership in the Community, Professor Lee will be committed to participating in WEF-initiated activities and events related to promising therapeutic interventions for mental disorders and future directions of artificial intelligence. Seven of this year’s WEF Young Scientists are from Asia, including Professor Lee, while eight are based in Europe. Six study in the Americas, two work in South Africa, and the remaining two in the Middle East. Fourteen, more than half, of the newly announced 25 Young Scientists are women. (END)
Ultrathin but Fully Packaged High-Resolution Camera
- Biologically inspired ultrathin arrayed camera captures super-resolution images. - The unique structures of biological vision systems in nature inspired scientists to design ultracompact imaging systems. A research group led by Professor Ki-Hun Jeong have made an ultracompact camera that captures high-contrast and high-resolution images. Fully packaged with micro-optical elements such as inverted micro-lenses, multilayered pinhole arrays, and gap spacers on the image sensor, the camera boasts a total track length of 740 μm and a field of view of 73°. Inspired by the eye structures of the paper wasp species Xenos peckii, the research team completely suppressed optical noise between micro-lenses while reducing camera thickness. The camera has successfully demonstrated high-contrast clear array images acquired from tiny micro lenses. To further enhance the image quality of the captured image, the team combined the arrayed images into one image through super-resolution imaging. An insect’s compound eye has superior visual characteristics, such as a wide viewing angle, high motion sensitivity, and a large depth of field while maintaining a small volume of visual structure with a small focal length. Among them, the eyes of Xenos peckii and an endoparasite found on paper wasps have hundreds of photoreceptors in a single lens unlike conventional compound eyes. In particular, the eye structures of an adult Xenos peckii exhibit hundreds of photoreceptors on an individual eyelet and offer engineering inspiration for ultrathin cameras or imaging applications because they have higher visual acuity than other compound eyes. For instance, Xenos peckii’s eye-inspired cameras provide a 50 times higher spatial resolution than those based on arthropod eyes. In addition, the effective image resolution of the Xenos peckii’s eye can be further improved using the image overlaps between neighboring eyelets. This unique structure offers higher visual resolution than other insect eyes. The team achieved high-contrast and super-resolution imaging through a novel arrayed design of micro-optical elements comprising multilayered aperture arrays and inverted micro-lens arrays directly stacked over an image sensor. This optical component was integrated with a complementary metal oxide semiconductor image sensor. This is first demonstration of super-resolution imaging which acquires a single integrated image with high contrast and high resolving power reconstructed from high-contrast array images. It is expected that this ultrathin arrayed camera can be applied for further developing mobile devices, advanced surveillance vehicles, and endoscopes. Professor Jeong said, “This research has led to technological advances in imaging technology. We will continue to strive to make significant impacts on multidisciplinary research projects in the fields of microtechnology and nanotechnology, seeking inspiration from natural photonic structures.” This work was featured in Light Science & Applications last month and was supported by the National Research Foundation (NRF) of and the Ministry of Health and Welfare (MOHW) of Korea. Image credit: Professor Ki-Hun Jeong, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Kisoo Kim, Kyung-Won Jang, Jae-Kwan Ryu, and Ki-Hun Jeong. (2020) “Biologically inspired ultrathin arrayed camera for high-contrast and high-resolution imaging”. Light Science & Applications. Volume 9. Article 28. Available online at https://doi.org/10.1038/s41377-020-0261-8 Profile: Ki-Hun Jeong Professor firstname.lastname@example.org http://biophotonics.kaist.ac.kr/ Department of Bio and Brain Engineering KAIST Profile: Kisoo Kim Ph.D. Candidate email@example.com http://biophotonics.kaist.ac.kr/ Department of Bio and Brain Engineering KAIST (END)
A Single Biological Factor Predicts Distinct Cortical Organizations across Mammalian Species
-A KAIST team’s mathematical sampling model shows that retino-cortical mapping is a prime determinant in the topography of cortical organization.- Researchers have explained how visual cortexes develop uniquely across the brains of different mammalian species. A KAIST research team led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering has identified a single biological factor, the retino-cortical mapping ratio, that predicts distinct cortical organizations across mammalian species. This new finding has resolved a long-standing puzzle in understanding visual neuroscience regarding the origin of functional architectures in the visual cortex. The study published in Cell Reports on March 10 demonstrates that the evolutionary variation of biological parameters may induce the development of distinct functional circuits in the visual cortex, even without species-specific developmental mechanisms. In the primary visual cortex (V1) of mammals, neural tuning to visual stimulus orientation is organized into one of two distinct topographic patterns across species. While primates have columnar orientation maps, a salt-and-pepper type organization is observed in rodents. For decades, this sharp contrast between cortical organizations has spawned fundamental questions about the origin of functional architectures in the V1. However, it remained unknown whether these patterns reflect disparate developmental mechanisms across mammalian taxa, or simply originate from variations in biological parameters under a universal development process. To identify a determinant predicting distinct cortical organizations, Professor Paik and his researchers Jaeson Jang and Min Song examined the exact condition that generates columnar and salt-and-pepper organizations, respectively. Next, they applied a mathematical model to investigate how the topographic information of the underlying retinal mosaics pattern could be differently mapped onto a cortical space, depending on the mapping condition. The research team proved that the retino-cortical feedforwarding mapping ratio appeared to be correlated to the cortical organization of each species. In the model simulations, the team found that distinct cortical circuitries can arise from different V1 areas and retinal ganglion cell (RGC) mosaic sizes. The team’s mathematical sampling model shows that retino-cortical mapping is a prime determinant in the topography of cortical organization, and this prediction was confirmed by neural parameter analysis of the data from eight phylogenetically distinct mammalian species. Furthermore, the researchers proved that the Nyquist sampling theorem explains this parametric division of cortical organization with high accuracy. They showed that a mathematical model predicts that the organization of cortical orientation tuning makes a sharp transition around the Nyquist sampling frequency, explaining why cortical organizations can be observed in either columnar or salt-and-pepper organizations, but not in intermediates between these two stages. Professor Paik said, “Our findings make a significant impact for understanding the origin of functional architectures in the visual cortex of the brain, and will provide a broad conceptual advancement as well as advanced insights into the mechanism underlying neural development in evolutionarily divergent species.” He continued, “We believe that our findings will be of great interest to scientists working in a wide range of fields such as neuroscience, vision science, and developmental biology.” This work was supported by the National Research Foundation of Korea (NRF). Image credit: Professor Se-Bum Paik, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Jaeson Jang, Min Song, and Se-Bum Paik. (2020). Retino-cortical mapping ratio predicts columnar and salt-and-pepper organization in mammalian visual cortex. Cell Reports. Volume 30. Issue 10. pp. 3270-3279. Available online at https://doi.org/10.1016/j.celrep.2020.02.038 Profile: Se-Bum Paik Assistant Professor firstname.lastname@example.org http://vs.kaist.ac.kr/ VSNN Laboratory Department of Bio and Brain Engineering Program of Brain and Cognitive Engineering http://kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea Profile: Jaeson Jang Ph.D. Candidate email@example.com Department of Bio and Brain Engineering, KAIST Profile: Min Song Ph.D. Candidate firstname.lastname@example.org Program of Brain and Cognitive Engineering, KAIST (END)
Professor Jong Chul Ye Appointed as Distinguished Lecturer of IEEE EMBS
Professor Jong Chul Ye from the Department of Bio and Brain Engineering was appointed as a distinguished lecturer by the International Association of Electrical and Electronic Engineers (IEEE) Engineering in Medicine and Biology Society (EMBS). Professor Ye was invited to deliver a lecture on his leading research on artificial intelligence (AI) technology in medical video restoration. He will serve a term of two years beginning in 2020. IEEE EMBS's distinguished lecturer program is designed to educate researchers around the world on the latest trends and technology in biomedical engineering. Sponsored by IEEE, its members can attend lectures on the distinguished professor's research subject. Professor Ye said, "We are at a time where the importance of AI in medical imaging is increasing.” He added, “I am proud to be appointed as a distinguished lecturer of the IEEE EMBS in recognition of my contributions to this field.” (END)
New IEEE Fellow, Professor Jong Chul Ye
Professor Jong Chul Ye from the Department of Bio and Brain Engineering was named a new fellow of the Institute of Electrical and Electronics Engineers (IEEE). IEEE announced this on December 1 in recognition of Professor Ye’s contributions to the development of signal processing and artificial intelligence (AI) technology in the field of biomedical imaging. As the world’s largest society in the electrical and electronics field, IEEE names the top 0.1% of their members as fellows based on their research achievements.Professor Ye has published more than 100 research papers in world-leading journals in the biomedical imaging field, including those affiliated with IEEE. He also gave a keynote talk at the yearly conference of the International Society for Magnetic Resonance Imaging (ISMRM) on medical AI technology. In addition, Professor Ye has been appointed to serve as the next chair of the Computational Imaging Technical Committee of the IEEE Signal Processing Society, and the chair of the IEEE Symposium on Biomedical Imaging (ISBI) 2020 to be held in April in Iowa, USA. Professor Ye said, “The importance of AI technology is developing in the biomedical imaging field. I feel proud that my contributions have been internationally recognized and allowed me to be named an IEEE fellow.”
Professor Je-Kyun Park, Awarded by The Korean BioChip Society
On November 9, Je-Kyun Park from the Department of Bio and Brain Engineering at KAIST received an award from the 2017 Fall Meeting of The Korean BioChip Society held in Paradise Hotel Busan, Korea. This year’s meeting recognized Professor Park for developing lab-on-a-chip and microfluidic analytical technologies. The Korean BioChip Society is a corporation of biochip professional established in 2006 for the development of biochip technology. Every year, the Society selects a recipient based on the nominees’ academic achievements and contributions to bio-fusion industry. Professor Park served on the international editorial boards of renowned international journals in related fields, including Biosensors and Bioelectronics and Lab on a Chip. He was also the Committee Chairman of MicroTas in 2015.
Dr. Hyundoo Hwang Receives a Tenured Position at Monterrey Institute of Technology and Higher Education
Hyundoo Hwang, a former graduate student in the Department of Bio & Brain Engineering at KAIST, has been granted a tenured position at the Monterrey Institute of Technology and Higher Education (ITSEM), Mexico. Dr. Hwang received his bachelor’s, master’s, and doctoral degree at KAIST and started his professorship at Ulsan National Institute of Science & Technology (UNIST) in Korea. He continued his research in the United States as a professor at Georgia Institute of Technology. He has been acknowledged for the development of an advanced nanotechnology for the diagnosis of rare diseases and research in cell signals. He is one of the leading researchers in an international research project in microelectromechanical systems (MEMS) with participation by researchers from over ten countries. He has been active in commercializing biosensor technology in the U.S. and Mexico. Since its establishment in 1943, ITSEM has grown to 33 campuses in 25 cities in Mexico. It is the largest university in Latin America with over 90,000 students (47% of its graduate students has oversea research experience). It recruits over 5,000 international students and professors every year. Dr. Hwang will begin teaching at ITSEM as a professor in the Department of Biomedical Engineering (Ingeniería Biomédica) this fall. He will also conduct research in nano- and micro-technology as a member of Sensors and Devices research group. Professor Gwang Hyun Cho, head of KAIST's Department of Bio and Brain Engineering said that Dr. Hwang’s tenure professorship at ITSEM demonstrated that the academic program at KAIST—from undergraduate to doctoral—was on par with the international standard. He hoped that more talents from the department would seek academic careers in internationally renowned universities around the world.
Professor Kwang-Hyun Cho Recognzied by "Scientist of the Month" Award
Professor Kwang-Hyun Cho of KAIST’s Department of Bio and Brain Engineering received the “Scientist of the Month” award in February 2015 from the Ministry of Science, ICT, and Future Planning of the Republic of Korea and the National Research Foundation of Korea. The award was in recognition of Professor Cho’s contribution to the advanced technique of controlling the death of cancer cells based on systems biology, a convergence research in information technology (IT) and biotechnology. Professor Cho has published around 140 articles in international journals, including 34 papers in renowned science journals such as Nature, Science, and Cell in the past three years. His work also includes systems biology textbooks and many entries in international academic encyclopaedia. His field, systems biology, is a new biological research paradigm that identifies and controls the fundamental principles of organisms on a systems level. A well-known tumour suppressor protein, p53, is known to suppress abnormal cell growth and promote apoptosis of can cells, and thus was a focus of research by many scientists, but its effect has been insignificant and brought many side effects. This was due to the complex function of p53 that controls various positive and negative feedbacks. Therefore, there was a limit to understanding the protein with the existing biological approach. However, Professor Cho found the kinetic change and function of p53 via a systems biology approach. By applying IT technology to complex biological networks, he also identified the response to stress and the survival and death signal transduction pathways of cardiomyocytes and developed new control methods for cancer cells. Professor Cho said, “This award served as a momentum to turn over a new leaf.” He added, “I hope convergence research such as my field will bring more innovative ideas on the boundaries of academia.”
Newsweek: The Goosebump Sensor That Knows How You Feel
Newsweek covered the introduction of the goosebump sensor invented by Professor Young-Ho Cho of the Department of Bio and Brain Engineering at KAIST in an article dated July 27, 2014. The article entitled “The Goosebump Sensor That Knows How You Feel” explains how the sensor works and reports on the current research and development trends in emotion-sensing technology. Professor Cho’s research paper was originally published in the journal Applied Physics Letters on June 24, 2014, titled “A Flexible Skin Piloerection Monitoring Sensor." Newsweek, July 27, 2014 “The Goosebump Sensor That Knows How You Feel” http://www.newsweek.com/goosebump-sensor-knows-how-you-feel-260689
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.
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