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Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. )
The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection.
For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications.
The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin.
“In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.”
Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones.
“This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said.
By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy.
The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP.
“We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.”
The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2.
-Profile
Professor Ji-Joon Song
Department of Biological Sciences KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
2020.01.07 View 16142 -
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.”
2019.12.18 View 16812 -
Professor YongKeun Park Wins the 2018 Fumio Okano Award
(Professor Park)
Professor YongKeun Park from the Department of Physics won the 2018 Fumio Okano Award in recognition of his contributions to 3D display technology development during the annual conference of the International Society for Optics and Photonics (SPIE) held last month in Orlando, Florida in the US.
The Fumio Okano Best 3D Paper Prize is presented annually in memory of Dr. Fumio Okano, a pioneer and innovator of 3D displays who passed away in 2013, for his contributions to the field of 3D TVs and displays. The award is sponsored by NHK-ES.
Professor Park and his team are developing novel technology for measuring and visualizing 3D images by applying random light scattering. He has published numerous papers on 3D holographic camera technology and 3000x enhanced performance of 3D holographic displays in renowned international journals such as Nature Photonics, Nature Communications, and Science Advances. His technology has drawn international attention from renowned media outlets including Newsweek and Forbes.
He has established two startups to commercialize his technology. Tomocube specializes in 3D imaging microscopes using holotomographic technology and the company exports their products to several countries including the US and Japan. The.Wave.Talk is exploring technology for examining pre-existing bacteria anywhere and anytime.
Professor Park’s innovations have already been recognized in and out of KAIST. In February, he was selected as the KAISTian of the Year for his outstanding research, commercialization, and startups. He was also decorated with the National Science Award in April by the Ministry of Science and ICT and the Hong Jin-Ki Innovation Award later in May by the Yumin Cultural Foundation.
Professor Park said, “3D holography is emerging as a significant technology with growing potential and positive impacts on our daily lives. However, the current technology lags far behind the levels displayed in SF movies. We will do our utmost to reach this level with more commercialization."
2018.05.31 View 17942 -
Seong-Tae Kim Wins Robert-Wagner All-Conference Best Paper Award
(Ph.D. candidate Seong-Tae Kim)
Ph.D. candidate Seong-Tae Kim from the School of Electrical Engineering won the Robert Wagner All-Conference Best Student Paper Award during the 2018 International Society for Optics and Photonics (SPIE) Medical Imaging Conference, which was held in Houston last month.
Kim, supervised by Professor Yong Man Ro, received the award for his paper in the category of computer-aided diagnosis. His paper, titled “ICADx: Interpretable Computer-Aided Diagnosis of Breast Masses”, was selected as the best paper out of 900 submissions. The conference selects the best paper in nine different categories. His research provides new insights on diagnostic technology to detect breast cancer powered by deep learning.
2018.03.15 View 16414 -
Meet the KAISTian of 2017, Professor YongKeun Park
Professor YongKeun Park from the Department of Physics is one of the star professors in KAIST. Rising to the academic stardom, Professor Park’s daily schedule is filled with series of business meetings in addition to lab meetings and lectures.
The year 2017 must have been special for him. During the year, he published numerous papers in international journals, such as Nature Photonics, Nature Communications and Science Advances. These high performances drew international attention from renowned media, including Newsweek and Forbes. Moreover, recognizing his research performance, he was elected as a fellow member of the Optical Society (OSA) in his mid-30s. Noting that the members’ age ranges from late 50s to early 60s, Professor Park’s case considered to be quite exceptional.
Adding to his academic achievement, he has launched two startups powered of his own technologies. One is called Tomocube, a company specialized in 3-D imaging microscope using holotomography technology. His company is currently exporting the products to multiple countries, including the United States and Japan. The other one is The.Wave.Talk which has technologies for examining pre-existing bacteria anywhere and anytime.
His research career and entrepreneurship are well deserved recipient of many honors. At the 2018 kick-off ceremony, Professor Park was awarded the KAISTian of 2017 in recognition of his developing holographic measure and control technology as well as founding a new field for technology application.
KAISTian of the Year, first presented in 2001, is an award to recognize the achievements and exemplary contribution of KAIST member who has put significant effort nationally and internationally, enhancing the value of KAIST.
While receiving the award, he thanked his colleagues and his students who have achieved this far together. He said, “I would like to thank KAIST for providing environment for young professors like me so that we can engage themselves in research. Also, I would like to mention that I am an idea seeder and my students do the most of the research. So, I appreciate my students for their hard works, and it is very pleasure to have them. Lastly, I thank the professors for teaching these outstanding students. I feel great responsibility over this title. I will dedicate myself to make further progress in commercializing technology in KAIST.”
Expecting his successful startup cases as a model and great inspiration to students as well as professors, KAIST interviewed Professor Park.
Q What made you decide to found your startups?
A I believed that my research areas could be further used. As a professor, I believe that it is a university’s role to create added value through commercializing technology and creating startups.
Q You have co-founded two startups. What is your role in each company?
A So, basically I have two full-time jobs, professor in KAIST and CTO in Tomocube. After transferring the technology, I hold the position of advisor in The.Wave.Talk.
(Holographic images captured by the product Professor Park developed)
Q Do your students also participate in your companies or can they?
A No, the school and companies are separate spaces; in other words, they are not participating in my companies. They have trained my employees when transferring the technologies, but they are not directly working for the companies.
However, they can participate if they want to. If there’s a need to develop a certain technology, an industry-academia contract can be made. According to the agreement, students can work for the companies.
Q Were there any hardships when preparing the startups?
A At the initial stage, I did not have a financial problem, thanks to support from Startup KAIST. Yet, inviting capital is the beginning, and I think every step I made to operate, generate revenue, and so on is not easy.
Q Do you believe KAIST is startup-friendly?
A Yes, there’s no school like KAIST in Korea and any other country. Besides various programs to support startup activities, Startup KAIST has many professors equipped with a great deal of experience. Therefore, I believe that KAIST provides an excellent environment for both students and professors to create startups.
Q Do you have any suggestion to KAIST institutionally?
A Well, I would like to make a comment to students and professors in KAIST. I strongly recommend them to challenge themselves by launching startups if they have good ideas. Many students wish to begin their jobs in government-funded research institutes or major corporates, but I believe that engaging in a startup company will also give them valuable and very productive experience.
Unlike before, startup institutions are well established, so attracting good capital is not so hard. There are various activities offered by Startup KAIST, so it’s worthwhile giving it a try.
Q What is your goal for 2018 as a professor and entrepreneur?
A I don’t have a grand plan, but I will work harder to produce good students with new topics in KAIST while adding power to my companies to grow bigger.
By Se Yi Kim from the PR Office
2018.01.03 View 17529 -
Professor YongKeun Park Elected as a Fellow of the Optical Society
Professor YongKeun Park, from the Department of Physics at KAIST, was elected as a fellow member of the Optical Society (OSA) in Washington, D.C. on September 12. Fellow membership is given to members who have made a significant contribution to the advancement of optics and photonics.
Professor Park was recognized for his research on digital holography and wavefront control technology.
Professor Park has been producing outstanding research outcomes in the field of holographic technology and light scattering control since joining KAIST in 2010. In particular, he developed and commercialized technology for a holographic telescope. He applied it to various medical and biological research projects, leading the field worldwide.
In the past, cells needed to be dyed with fluorescent materials to capture a 3-D image. However, Professor Park’s holotomography (HT) technology can capture 3-D images of living cells and tissues in real time without color dyeing. This technology allows diversified research in the biological and medical field.
Professor Park established a company, Tomocube, Inc. in 2015 to commercialize the technology. In 2016, he received funding from SoftBank Ventures and Hanmi Pharmaceutical. Currently, major institutes, including MIT, the University of Pittsburgh, the German Cancer Research Center, and Seoul National University Hospital are using his equipment.
Recently, Professor Park and his team developed technology based on light scattering measurements. With this technology, they established a company called The Wave Talk and received funding from various organizations, such as NAVER. Its first product is about to be released.
Professor Park said, “I am glad to become a fellow member based on the research outcomes I produced since I was appointed as a professor at KAIST. I would like to thank the excellent researchers as well as the school for its support. I will devote myself to continuously producing novel outcomes in both basic and applied fields.”
Professor Park has published nearly 100 papers in renowned journals including Nature Photonics, Nature Communications, Science Advances, and Physical Review Letters.
2017.10.18 View 19042 -
Professor Jinah Park Received the Prime Minister's Award
Professor Jinah Park of the School of Computing received the Prime Minister’s Citation Ribbon on April 21 at a ceremony celebrating the Day of Science and ICT. The awardee was selected by the Ministry of Science, ICT and Future Planning and Korea Communications Commission.
Professor Park was recognized for her convergence R&D of a VR simulator for dental treatment with haptic feedback, in addition to her research on understanding 3D interaction behavior in VR environments. Her major academic contributions are in the field of medical imaging, where she developed a computational technique to analyze cardiac motion from tagging data.
Professor Park said she was very pleased to see her twenty-plus years of research on ways to converge computing into medical areas finally bear fruit. She also thanked her colleagues and students in her Computer Graphics and CGV Research Lab for working together to make this achievement possible.
2017.04.26 View 15856 -
Next-Generation Holographic Microscope for 3D Live Cell Imaging
KAIST researchers have developed a revolutionary bio-medical imaging tool, the HT-1, to view and analyze cells, which is commercially available.
Professor YongKeun Park of the Physics Department at KAIST and his research team have developed a powerful method for 3D imaging of live cells without staining. The researchers announced the launch of their new microscopic tool, the holotomography (HT)-1, to the global marketplace through a Korean start-up that Professor Park co-founded, TomoCube (www.tomocube.com).
Professor Park is a leading researcher in the field of biophotonics and has dedicated much of his research career to working on digital holographic microscopy technology. He collaborated with TomoCube’s R&D team to develop a state-of-the-art, 2D/3D/4D holographic microscope that would allow a real-time label-free visualization of biological cells and tissues.
The HT is an optical analogy of X-ray computed tomography (CT). Both X-ray CT and HT share the same physical principle—the inverse of wave scattering. The difference is that HT uses laser illumination whereas X-ray CT uses X-ray beams. From the measurement of multiple 2D holograms of a cell, coupled with various angles of laser illuminations, the 3D refractive index (RI) distribution of the cell can be reconstructed. The reconstructed 3D RI map provides structural and chemical information of the cell including mass, morphology, protein concentration, and dynamics of the cellular membrane.
The HT enables users to quantitatively and non-invasively investigate the intrinsic properties of biological cells, for example, dry mass and protein concentration. Some of the research team’s breakthroughs that have leveraged HT’s unique and special capabilities can be found in several recent publications, including a lead article on the simultaneous 3D visualization and position tracking of optically trapped particles which was published in Optica on April 20, 2015.
Current fluorescence confocal microscopy techniques require the use of exogenous labeling agents to render high-contrast molecular information. Therefore, drawbacks include possible photo-bleaching, photo-toxicity, and interference with normal molecular activities. Immune or stem cells that need to be reinjected into the body are considered particularly difficult to employ with fluorescence microscopy.
“As one of the two currently available, high-resolution tomographic microscopes in the world, I believe that the HT-1 is the best in class regarding specifications and functionality. Users can see 3D/4D live images of cells, without fixing, coating or staining cells. Sample preparation times are reduced from a few days or hours to just a few minutes,” said Professor Park.
Two Korean hospitals, Seoul National University Hospital in Bundang and Boramae Hospital in Seoul, are using this microscope currently. The research team has also introduced the HT-1 at the Photonics West Exhibition 2016 that took place on February 16-18 in San Francisco, USA.
Professor Park added, “Our technology has set a new paradigm for cell observation under a microscope. I expect that this tomographic microscopy will be more widely used in future in various areas of pharmaceuticals, neuroscience, immunology, hematology, and cell biology.”
Figure 1: HT-1 and Its Specifications
Figure 2: 3D Images of Representative Biological Cells Taken with the HT-1
2016.03.29 View 16696 -
Ph.D. Candidate Seo Wins the Human Tech Paper Award
Hyun-Suk Seo, a doctoral student of KAIST’s Department of Electrical Engineering, received the grand prize of the “22nd Human Tech Paper Award” on February 3, 2016 from Samsung Electronics Co., Ltd.
Seo was the first to receive this prize ever since the Human Tech Paper Award was established 22 years ago. Until last year, the highest prize awarded for KAIST was a gold one.
The “Human Tech Paper Award” was established in 1994 by Samsung Electronics to discover and support outstanding scientists in the field of electrical engineering.
Entitled “Self-Gated Cardiac Cine MRI Using Phase Information,” Seo’s paper presented a technology that would reduce discomforts and inconveniences experienced by patients who take a magnetic resonance imaging (MRI).
This technology uses the speed changes of aorta and the abdominal movements of body to obtain the phase changes of magnetic resonance signals so that MRIs may be taken despite the organs’ movements.
Seo commented on his research, “I wanted to develop a technique that can make MRI a more comfortable experience. I will continue my research on this subject and hope to serve the needs of the society.”
In addition, the “Special Award,” which is given to schools, was awarded to KAIST. KAIST’s Department of Electrical Engineering has also been named the department that has received the second most awards (15 awards) this year.
Oh-Hyun Kwon, Vice President of Samsung Electronics, Steve Kang, President of KAIST, and Nak-In Seo, President of Seoul National University, participated in the event.
Picture: Hyun-Suk Seo (left), the recipient of the grand prize of the 2016 Human Tech Paper Award, and Oh-Hyun Kwon (right), Vice President of Samsung Electronics
2016.02.06 View 14619 -
IdeasLab Presents Biotechnology Solutions for Aging Populations at 2016 Davos Forum
KAIST researchers will discuss how biological sciences and health technologies can address challenges and opportunities posed by aging populations in an era of increasing longevity.
Many countries around the world today are experiencing the rapid growth of aging populations, with a decline in fertility rate and longer life expectancy.
At this year's Annual Meeting of the World Economic Forum (a.k.a. Davos Forum) on January 20-23, 2016 in Davos-Klosters, Switzerland, four researchers in the field of biological sciences and biotechnology at the Korea Advanced Institute of Science and Technology (KAIST) will discuss the implications of an aging population and explore possible solutions to provide better health care services to the elderly.
KAIST will host an IdeasLab twice on the theme "Biotechnology Solutions for Ageing Populations" on January 21st and 23rd, respectively.
Professor Byung-Kwan Cho of the Biological Sciences Department will give a presentation on "Rejuvenation via the Microbiome," explaining how microorganisms in the human gut play an important role in preventing aging, or even rejuvenating it.
Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department will talk about "Traditional Medicine Reimagined through Modern Systems Biology." Professor Lee will introduce his research results published in Nature Biotechnology (March 6, 2015) and some more new results. He discovered the mechanisms of traditional oriental medicine's (TOM) efficacy by applying systems biology to study structural similarities between natural and nontoxic multi-compounds in the medicine and human metabolites. He will discuss TOM's multi-target approach, which is based on the synergistic combinations of multi-compounds to treat symptoms of a disease, can contribute to the development of new drugs, cosmetics, and nutrients.
Professor Youn-Kyung Lim of the Industrial Design Department will speak about a mobile and the Internet of Things-based health care service called "Dr. M" in her presentation on "Advanced Mobile Healthcare Systems."
Professor Daesoo Kim of the Biological Sciences Department will share his research on human's happiness and greed in the context of nueroscience and behavioral and biological sciences in a talk entitled "A Neural Switch for Being Happy with Less on a Crowded Planet."
KAIST has hosted IdeasLabs several times at the Summer Davos Forum in China, but this is the first time it will participate in the Davos Forum in January.
Professor Lee said, "Just like climate change, the issue of how to address aging populations has become a major global issue. We will share some exciting research results and hope to have in depth discussion on this issue with the leaders attending the Davos Forum. KAIST will engage actively in finding solutions that benefit not only Korea but also the international community."
2016.01.19 View 16019 -
Professor Mikyoung Lim Receives the MediaV Young Researcher Award
Professor Mikyoung Lim of the Department of Mathematical Sciences at KAIST received the MediaV Young Researchers Award at the International Conference on Inverse Problems and Related Topics that took place at the National Taiwan University, Taiwan, on December 15-19, 2014.
The Conference established the MediaV Young Researcher Award in 2010 to recognize distinguished scholars who are age 40 or younger and have made important contributions to the field of inverse problems. This year, two recipients were chosen for the award.
Professor Lim has focused her research on the incremental reading of incomprehensible materials’ imaging and the effect of invisibility cloaking.
The other awardee was Kui Ren, a professor at the University of Texas at Austin.
2014.12.27 View 16286 -
Tae-Wan Kim, a doctoral candidate, receives the best paper award from ECTC
The 2014 Electronic Components and Technology Conference (ECTC) will take place on May 27-30 in Florida, USA. Tae-Wan Kim, a Ph.D. candidate at the Department of Materials Science Engineering (MSE), KAIST, will receive the Intel Best Student Paper Award at the conference.ECTC is the premier international conference that brings together the best researchers and engineers in packaging, components and microelectronic systems science, technology and education in an environment of cooperation and technical exchange. The conference is sponsored by the Components, Packaging and Manufacturing Technology (CPMT) Society of IEEE (Institute of Electrical and Electronics Engineering).The paper describes research on novel nanofiber anisotropic conductive films for ultra fine pitch electronic package application, which was written under the guidance of Professor Kyung-Wook Paik of the MSE Department. In the past ten years, two of his students have received the best paper award from ECTC.
2014.03.14 View 17334