aging
-
Streamlining the Process of Materials Discovery
The materials platform M3I3 reduces the time for materials discovery by reverse engineering future materials using multiscale/multimodal imaging and machine learning of the processing-structure-properties relationship
Developing new materials and novel processes has continued to change the world. The M3I3 Initiative at KAIST has led to new insights into advancing materials development by implementing breakthroughs in materials imaging that have created a paradigm shift in the discovery of materials. The Initiative features the multiscale modeling and imaging of structure and property relationships and materials hierarchies combined with the latest material-processing data.
The research team led by Professor Seungbum Hong analyzed the materials research projects reported by leading global institutes and research groups, and derived a quantitative model using machine learning with a scientific interpretation. This process embodies the research goal of the M3I3: Materials and Molecular Modeling, Imaging, Informatics and Integration.
The researchers discussed the role of multiscale materials and molecular imaging combined with machine learning and also presented a future outlook for developments and the major challenges of M3I3. By building this model, the research team envisions creating desired sets of properties for materials and obtaining the optimum processing recipes to synthesize them.
“The development of various microscopy and diffraction tools with the ability to map the structure, property, and performance of materials at multiscale levels and in real time enabled us to think that materials imaging could radically accelerate materials discovery and development,” says Professor Hong.
“We plan to build an M3I3 repository of searchable structural and property maps using FAIR (Findable, Accessible, Interoperable, and Reusable) principles to standardize best practices as well as streamline the training of early career researchers.”
One of the examples that shows the power of structure-property imaging at the nanoscale is the development of future materials for emerging nonvolatile memory devices. Specifically, the research team focused on microscopy using photons, electrons, and physical probes on the multiscale structural hierarchy, as well as structure-property relationships to enhance the performance of memory devices.
“M3I3 is an algorithm for performing the reverse engineering of future materials. Reverse engineering starts by analyzing the structure and composition of cutting-edge materials or products. Once the research team determines the performance of our targeted future materials, we need to know the candidate structures and compositions for producing the future materials.”
The research team has built a data-driven experimental design based on traditional NCM (nickel, cobalt, and manganese) cathode materials. With this, the research team expanded their future direction for achieving even higher discharge capacity, which can be realized via Li-rich cathodes.
However, one of the major challenges was the limitation of available data that describes the Li-rich cathode properties. To mitigate this problem, the researchers proposed two solutions: First, they should build a machine-learning-guided data generator for data augmentation. Second, they would use a machine-learning method based on ‘transfer learning.’ Since the NCM cathode database shares a common feature with a Li-rich cathode, one could consider repurposing the NCM trained model for assisting the Li-rich prediction. With the pretrained model and transfer learning, the team expects to achieve outstanding predictions for Li-rich cathodes even with the small data set.
With advances in experimental imaging and the availability of well-resolved information and big data, along with significant advances in high-performance computing and a worldwide thrust toward a general, collaborative, integrative, and on-demand research platform, there is a clear confluence in the required capabilities of advancing the M3I3 Initiative.
Professor Hong said, “Once we succeed in using the inverse “property−structure−processing” solver to develop cathode, anode, electrolyte, and membrane materials for high energy density Li-ion batteries, we will expand our scope of materials to battery/fuel cells, aerospace, automobiles, food, medicine, and cosmetic materials.”
The review was published in ACS Nano in March. This study was conducted through collaborations with Dr. Chi Hao Liow, Professor Jong Min Yuk, Professor Hye Ryung Byon, Professor Yongsoo Yang, Professor EunAe Cho, Professor Pyuck-Pa Choi, and Professor Hyuck Mo Lee at KAIST, Professor Joshua C. Agar at Lehigh University, Dr. Sergei V. Kalinin at Oak Ridge National Laboratory, Professor Peter W. Voorhees at Northwestern University, and Professor Peter Littlewood at the University of Chicago (Article title: Reducing Time to Discovery: Materials and Molecular Modeling, Imaging, Informatics, and Integration).This work was supported by the KAIST Global Singularity Research Program for 2019 and 2020.
Publication:
“Reducing Time to Discovery: Materials and Molecular Modeling, Imaging, Informatics and Integration,” S. Hong, C. H. Liow, J. M. Yuk, H. R. Byon, Y. Yang, E. Cho, J. Yeom, G. Park, H. Kang, S. Kim, Y. Shim, M. Na, C. Jeong, G. Hwang, H. Kim, H. Kim, S. Eom, S. Cho, H. Jun, Y. Lee, A. Baucour, K. Bang, M. Kim, S. Yun, J. Ryu, Y. Han, A. Jetybayeva, P.-P. Choi, J. C. Agar, S. V. Kalinin, P. W. Voorhees, P. Littlewood, and H. M. Lee, ACS Nano 15, 3, 3971–3995 (2021) https://doi.org/10.1021/acsnano.1c00211
Profile:
Seungbum Hong, PhD
Associate Professor
seungbum@kaist.ac.kr
http://mii.kaist.ac.kr
Department of Materials Science and Engineering
KAIST
(END)
2021.04.05 View 13015 -
Simulations Open a New Way to Reverse Cell Aging
Turning off a newly identified enzyme could reverse a natural aging process in cells.
Research findings by a KAIST team provide insight into the complex mechanism of cellular senescence and present a potential therapeutic strategy for reducing age-related diseases associated with the accumulation of senescent cells.
Simulations that model molecular interactions have identified an enzyme that could be targeted to reverse a natural aging process called cellular senescence. The findings were validated with laboratory experiments on skin cells and skin equivalent tissues, and published in the Proceedings of the National Academy of Sciences (PNAS).
“Our research opens the door for a new generation that perceives aging as a reversible biological phenomenon,” says Professor Kwang-Hyun Cho of the Department of Bio and Brain engineering at the Korea Advanced Institute of Science and Technology (KAIST), who led the research with colleagues from KAIST and Amorepacific Corporation in Korea.
Cells respond to a variety of factors, such as oxidative stress, DNA damage, and shortening of the telomeres capping the ends of chromosomes, by entering a stable and persistent exit from the cell cycle. This process, called cellular senescence, is important, as it prevents damaged cells from proliferating and turning into cancer cells. But it is also a natural process that contributes to aging and age-related diseases. Recent research has shown that cellular senescence can be reversed. But the laboratory approaches used thus far also impair tissue regeneration or have the potential to trigger malignant transformations.
Professor Cho and his colleagues used an innovative strategy to identify molecules that could be targeted for reversing cellular senescence. The team pooled together information from the literature and databases about the molecular processes involved in cellular senescence. To this, they added results from their own research on the molecular processes involved in the proliferation, quiescence (a non-dividing cell that can re-enter the cell cycle) and senescence of skin fibroblasts, a cell type well known for repairing wounds. Using algorithms, they developed a model that simulates the interactions between these molecules. Their analyses allowed them to predict which molecules could be targeted to reverse cell senescence.
They then investigated one of the molecules, an enzyme called PDK1, in incubated senescent skin fibroblasts and three-dimensional skin equivalent tissue models. They found that blocking PDK1 led to the inhibition of two downstream signalling molecules, which in turn restored the cells’ ability to enter back into the cell cycle. Notably, the cells retained their capacity to regenerate wounded skin without proliferating in a way that could lead to malignant transformation.
The scientists recommend investigations are next done in organs and organisms to determine the full effect of PDK1 inhibition. Since the gene that codes for PDK1 is overexpressed in some cancers, the scientists expect that inhibiting it will have both anti-aging and anti-cancer effects.
-Profile
Professor Kwang-Hyun Cho
Laboratory for Systems Biology and Bio-Inspired Engineering
http://sbie.kaist.ac.kr
Department of Bio and Brain Engineering
KAIST
2020.11.26 View 12520 -
Microscopy Approach Poised to Offer New Insights into Liver Diseases
Researchers have developed a new way to visualize the progression of nonalcoholic fatty liver disease (NAFLD) in mouse models of the disease. The new microscopy method provides a high-resolution 3D view that could lead to important new insights into NAFLD, a condition in which too much fat is stored in the liver.
“It is estimated that a quarter of the adult global population has NAFLD, yet an effective treatment strategy has not been found,” said professor Pilhan Kim from the Graduate School of Medical Science and Engineering at KAIST. “NAFLD is associated with obesity and type 2 diabetes and can sometimes progress to liver failure in serious case.”
In the Optical Society (OSA) journal Biomedical Optics Express, Professor Kim and colleagues reported their new imaging technique and showed that it can be used to observe how tiny droplets of fat, or lipids, accumulate in the liver cells of living mice over time.
“It has been challenging to find a treatment strategy for NAFLD because most studies examine excised liver tissue that represents just one timepoint in disease progression,” said Professor Kim. “Our technique can capture details of lipid accumulation over time, providing a highly useful research tool for identifying the multiple parameters that likely contribute to the disease and could be targeted with treatment.”
Capturing the dynamics of NAFLD in living mouse models of the disease requires the ability to observe quickly changing interactions of biological components in intact tissue in real-time. To accomplish this, the researchers developed a custom intravital confocal and two-photon microscopy system that acquires images of multiple fluorescent labels at video-rate with cellular resolution.
“With video-rate imaging capability, the continuous movement of liver tissue in live mice due to breathing and heart beating could be tracked in real time and precisely compensated,” said Professor Kim. “This provided motion-artifact free high-resolution images of cellular and sub-cellular sized individual lipid droplets.”
The key to fast imaging was a polygonal mirror that rotated at more than 240 miles per hour to provide extremely fast laser scanning. The researchers also incorporated four different lasers and four high-sensitivity optical detectors into the setup so that they could acquire multi-color images to capture different color fluorescent probes used to label the lipid droplets and microvasculature in the livers of live mice.
“Our approach can capture real-time changes in cell behavior and morphology, vascular structure and function, and the spatiotemporal localization of biological components while directly visualizing of lipid droplet development in NAFLD progression,” said Professor Kim. “It also allows the analysis of the highly complex behaviors of various immune cells as NAFLD progresses.”
The researchers demonstrated their approach by using it to observe the development and spatial distribution of lipid droplets in individual mice with NAFLD induced by a methionine and choline-deficient diet. Next, they plan to use it to study how the liver microenvironment changes during NAFLD progression by imaging the same mouse over time. They also want to use their microscope technique to visualize various immune cells and lipid droplets to better understand the complex liver microenvironment in NAFLD progression.
2020.08.21 View 9061 -
Tinkering with Roundworm Proteins Offers Hope for Anti-aging Drugs
- The somatic nuclear protein kinase VRK-1 increases the worm’s lifespan through AMPK activation, and this mechanism can be applied to promoting human longevity, the study reveals. -
KAIST researchers have been able to dial up and down creatures’ lifespans by altering the activity of proteins found in roundworm cells that tell them to convert sugar into energy when their cellular energy is running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings were published on July 1 in Science Advances.
The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing, enjoyed a boost in its lifespan when researchers tinkered with a couple of proteins involved in monitoring the energy use by its cells.
The proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status.
Using a range of different biological research tools, including introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at KAIST were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. This gene has remained pretty much unchanged throughout evolution. Most complex organisms have this same gene, including humans.
Lead author of the study Sangsoon Park and his colleagues confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks, and the inhibition of VRK-1 production reduced its lifespan.
The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into the energy “currency” that cells spend to do everything they need to do.
It is already known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in aging, and declines in the functioning of mitochondria are associated with age-related diseases. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals.
When the research team performed similar tinkering with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms.
“This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity, and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained Professor Lee.
At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria.
But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried out to better understand how VRK-1 works to activate AMPK, as well as figure out the precise mechanics of how AMPK controls cellular energy.
This work was supported by the National Research Foundation (NRF), and the Ministry of Science and ICT (MSIT) of Korea.
Image credit: Seung-Jae V. LEE, 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:
Park, S., et al. (2020) ‘VRK-1 extends life span by activation of AMPK via phosphorylation’. Science Advances, Volume 6. No. 27, eaaw7824. Available online at https://doi.org/10.1126/sciadv.aaw7824
Profile: Seung-Jae V. Lee, Ph.D.
Professor
seungjaevlee@kaist.ac.kr
https://sites.google.com/view/mgakaist
Molecular Genetics of Aging Laboratory
Department of Biological Sciences
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.krDaejeon 34141, Korea
(END)
2020.07.31 View 11981 -
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
sbpaik@kaist.ac.kr
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)
2020.06.08 View 13487 -
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)
2020.05.26 View 11782 -
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
kjeong@kaist.ac.kr
http://biophotonics.kaist.ac.kr/
Department of Bio and Brain Engineering
KAIST
Profile:
Kisoo Kim
Ph.D. Candidate
kisoo.kim1@kaist.ac.kr
http://biophotonics.kaist.ac.kr/
Department of Bio and Brain Engineering
KAIST
(END)
2020.03.23 View 17435 -
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)
2020.02.27 View 10132 -
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 10107 -
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 9426 -
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 10467 -
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 10148