research
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DeepTFactor Predicts Transcription Factors
A deep learning-based tool predicts transcription factors using protein sequences as inputs
A joint research team from KAIST and UCSD has developed a deep neural network named DeepTFactor that predicts transcription factors from protein sequences. DeepTFactor will serve as a useful tool for understanding the regulatory systems of organisms, accelerating the use of deep learning for solving biological problems.
A transcription factor is a protein that specifically binds to DNA sequences to control the transcription initiation. Analyzing transcriptional regulation enables the understanding of how organisms control gene expression in response to genetic or environmental changes. In this regard, finding the transcription factor of an organism is the first step in the analysis of the transcriptional regulatory system of an organism.
Previously, transcription factors have been predicted by analyzing sequence homology with already characterized transcription factors or by data-driven approaches such as machine learning. Conventional machine learning models require a rigorous feature selection process that relies on domain expertise such as calculating the physicochemical properties of molecules or analyzing the homology of biological sequences. Meanwhile, deep learning can inherently learn latent features for the specific task.
A joint research team comprised of Ph.D. candidate Gi Bae Kim and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, and Ye Gao and Professor Bernhard O. Palsson of the Department of Biochemical Engineering at UCSD reported a deep learning-based tool for the prediction of transcription factors. Their research paper “DeepTFactor: A deep learning-based tool for the prediction of transcription factors” was published online in PNAS.
Their article reports the development of DeepTFactor, a deep learning-based tool that predicts whether a given protein sequence is a transcription factor using three parallel convolutional neural networks. The joint research team predicted 332 transcription factors of Escherichia coli K-12 MG1655 using DeepTFactor and the performance of DeepTFactor by experimentally confirming the genome-wide binding sites of three predicted transcription factors (YqhC, YiaU, and YahB).
The joint research team further used a saliency method to understand the reasoning process of DeepTFactor. The researchers confirmed that even though information on the DNA binding domains of the transcription factor was not explicitly given the training process, DeepTFactor implicitly learned and used them for prediction. Unlike previous transcription factor prediction tools that were developed only for protein sequences of specific organisms, DeepTFactor is expected to be used in the analysis of the transcription systems of all organisms at a high level of performance.
Distinguished Professor Sang Yup Lee said, “DeepTFactor can be used to discover unknown transcription factors from numerous protein sequences that have not yet been characterized. It is expected that DeepTFactor will serve as an important tool for analyzing the regulatory systems of organisms of interest.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation of Korea.
-Publication
Gi Bae Kim, Ye Gao, Bernhard O. Palsson, and Sang Yup Lee. DeepTFactor: A deep learning-based tool for the prediction of transcription factors. (https://doi.org/10.1073/pnas202117118)
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
Metabolic &Biomolecular Engineering National Research Laboratory
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
2021.01.05 View 7855 -
Extremely Stable Perovskite Nanoparticles Films for Next-Generation Displays
Researchers have reported an extremely stable cross-linked perovskite nanoparticle that maintains a high photoluminescence quantum yield (PLQY) for 1.5 years in air and harsh liquid environments. This stable material’s design strategies, which addressed one of the most critical problems limiting their practical application, provide a breakthrough for the commercialization of perovskite nanoparticles in next-generation displays and bio-related applications.
According to the research team led by Professor Byeong-Soo Bae, their development can survive in severe environments such as water, various polar solvents, and high temperature with high humidity without additional encapsulation. This development is expected to enable perovskite nanoparticles to be applied to high color purity display applications as a practical color converting material. This result was published as the inside front cover article in Advanced Materials.
Perovskites, which consist of organics, metals, and halogen elements, have emerged as key elements in various optoelectronic applications. The power conversion efficiency of photovoltaic cells based on perovskites light absorbers has been rapidly increased. Perovskites are also great promise as a light emitter in display applications because of their low material cost, facile wavelength tunability, high (PLQY), very narrow emission band width, and wider color gamut than inorganic semiconducting nanocrystals and organic emitters. Thanks to these advantages, perovskites have been identified as a key color-converting material for next-generation high color-purity displays. In particular, perovskites are the only luminescence material that meets Rec. 2020 which is a new color standard in display industry.
However, perovskites are very unstable against heat, moisture, and light, which makes them almost impossible to use in practical applications. To solve these problems, many researchers have attempted to physically prevent perovskites from coming into contact with water molecules by passivating the perovskite grain and nanoparticle surfaces with organic ligands or inorganic shell materials, or by fabricating perovskite-polymer nanocomposites. These methods require complex processes and have limited stability in ambient air and water. Furthermore, stable perovskite nanoparticles in the various chemical environments and high temperatures with high humidity have not been reported yet.
The research team in collaboration with Seoul National University develops siloxane-encapsulated perovskite nanoparticle composite films. Here, perovskite nanoparticles are chemically crosslinked with thermally stable siloxane molecules, thereby significantly improving the stability of the perovskite nanoparticles without the need for any additional protecting layer.
Siloxane-encapsulated perovskite nanoparticle composite films exhibited a high PLQY (> 70%) value, which can be maintained over 600 days in water, various chemicals (alcohol, strong acidic and basic solutions), and high temperatures with high humidity (85℃/85%). The research team investigated the mechanisms impacting the chemical crosslinking and water molecule-induced stabilization of perovskite nanoparticles through various photo-physical analysis and density-functional theory calculation.
The research team confirmed that displays based on their siloxane-perovskite nanoparticle composite films exhibited higher PLQY and a wider color gamut than those of Cd-based quantum dots and demonstrated perfect color converting properties on commercial mobile phone screens. Unlike what was commonly believed in the halide perovskite field, the composite films showed excellent bio-compatibility because the siloxane matrix prevents the toxicity of Pb in perovskite nanoparticle.
By using this technology, the instability of perovskite materials, which is the biggest challenge for practical applications, is greatly improved through simple encapsulation method.
“Perovskite nanoparticle is the only photoluminescent material that can meet the next generation display color standard. Nevertheless, there has been reluctant to commercialize it due to its moisture vulnerability. The newly developed siloxane encapsulation technology will trigger more research on perovskite nanoparticles as color conversion materials and will accelerate early commercialization,” Professor Bae said.
This work was supported by the Wearable Platform Materials Technology Center (WMC) of the Engineering Research Center (ERC) Project, and the Leadership Research Program funded by the National Research Foundation of Korea.
-Publication:
Junho Jang, Young-Hoon Kim, Sunjoon Park, Dongsuk Yoo, Hyunjin Cho, Jinhyeong Jang, Han Beom Jeong, Hyunhwan Lee, Jong Min Yuk, Chan Beum Park, Duk Young Jeon, Yong-Hyun Kim, Byeong-Soo Bae, and Tae-Woo Lee. “Extremely Stable Luminescent Crosslinked Perovskite Nanoparticles under Harsh Environments over 1.5 Years” Advanced Materials, 2020, 2005255. https://doi.org/10.1002/adma.202005255.
Link to download the full-text paper:
https://onlinelibrary.wiley.com/doi/10.1002/adma.202005255
-Profile: Prof. Byeong-Soo Bae (Corresponding author)
bsbae@kaist.ac.kr
Lab. of Optical Materials & Coating
Department of Materials Science and Engineering
Korea Advanced Institute of Science and Technology (KAIST)
2020.12.29 View 10987 -
Astrocytes Eat Connections to Maintain Plasticity in Adult Brains
Developing brains constantly sprout new neuronal connections called synapses as they learn and remember. Important connections — the ones that are repeatedly introduced, such as how to avoid danger — are nurtured and reinforced, while connections deemed unnecessary are pruned away. Adult brains undergo similar pruning, but it was unclear how or why synapses in the adult brain get eliminated.
Now, a team of KAIST researchers has found the mechanism underlying plasticity and, potentially, neurological disorders in adult brains. They published their findings on December 23 in Nature.
“Our findings have profound implications for our understanding of how neural circuits change during learning and memory, as well as in diseases,” said paper author Won-Suk Chung, an assistant professor in the Department of Biological Sciences at KAIST. “Changes in synapse number have strong association with the prevalence of various neurological disorders, such as autism spectrum disorder, schizophrenia, frontotemporal dementia, and several forms of seizures.”
Gray matter in the brain contains microglia and astrocytes, two complementary cells that, among other things, support neurons and synapses. Microglial are a frontline immunity defense, responsible for eating pathogens and dead cells, and astrocytes are star-shaped cells that help structure the brain and maintain homeostasis by helping to control signaling between neurons. According to Professor Chung, it is generally thought that microglial eat synapses as part of its clean-up effort in a process known as phagocytosis.
“Using novel tools, we show that, for the first time, it is astrocytes and not microglia that constantly eliminate excessive and unnecessary adult excitatory synaptic connections in response to neuronal activity,” Professor Chung said. “Our paper challenges the general consensus in this field that microglia are the primary synapse phagocytes that control synapse numbers in the brain.”
Professor Chung and his team developed a molecular sensor to detect synapse elimination by glial cells and quantified how often and by which type of cell synapses were eliminated. They also deployed it in a mouse model without MEGF10, the gene that allows astrocytes to eliminate synapses. Adult animals with this defective astrocytic phagocytosis had unusually increased excitatory synapse numbers in the hippocampus. Through a collaboration with Dr. Hyungju Park at KBRI, they showed that these increased excitatory synapses are functionally impaired, which cause defective learning and memory formation in MEGF10 deleted animals.
“Through this process, we show that, at least in the adult hippocampal CA1 region, astrocytes are the major player in eliminating synapses, and this astrocytic function is essential for controlling synapse number and plasticity,” Chung said.
Professor Chung noted that researchers are only beginning to understand how synapse elimination affects maturation and homeostasis in the brain. In his group’s preliminary data in other brain regions, it appears that each region has different rates of synaptic elimination by astrocytes. They suspect a variety of internal and external factors are influencing how astrocytes modulate each regional circuit, and plan to elucidate these variables.
“Our long-term goal is understanding how astrocyte-mediated synapse turnover affects the initiation and progression of various neurological disorders,” Professor Chung said. “It is intriguing to postulate that modulating astrocytic phagocytosis to restore synaptic connectivity may be a novel strategy in treating various brain disorders.”
This work was supported by the Samsung Science & Technology Foundation, the National Research Foundation of Korea, and the Korea Brain Research Institute basic research program.
Other contributors include Joon-Hyuk Lee and Se Young Lee, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST); Ji-young Kim, Hyoeun Lee and Hyungju Park; Research Group for Neurovascular Unit, Korea Brain Research Institute (KBRI); Seulgi Noh, and Ji Young Mun, Research Group for Neural Circuit, KBRI. Kim, Noh and Park are also affiliated with the Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST).
-Profile
Professor Won-Suk Chung
Department of Biological Sciences
Gliabiology Lab (https://www.kaistglia.org/)
KAIST
-Publication
"Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis"
https://doi.org/10.1038/s41586-020-03060-3
2020.12.24 View 10152 -
Electrosprayed Micro Droplets Help Kill Bacteria and Viruses
With COVID-19 raging around the globe, researchers are doubling down on methods for developing diverse antimicrobial technologies that could be effective in killing a virus, but harmless to humans and the environment.
A recent study by a KAIST research team will be one of the responses to such efforts. Professor Seung Seob Lee and Dr. Ji-hun Jeong from the Department of Mechanical Engineering developed a harmless air sterilization prototype featuring electrosprayed water from a polymer micro-nozzle array. This study is one of the projects being supported by the KAIST New Deal R&D Initiative in response to COVID-19. Their study was reported in Polymer.
The electrosprayed microdroplets encapsulate reactive oxygen species such as hydroxyl radicals, superoxides that are known to have an antimicrobial function. The encapsulation prolongs the life of reactive oxygen species, which enable the droplets to perform their antimicrobial function effectively. Prior research has already proven the antimicrobial and encapsulation effects of electrosprayed droplets.
Despite its potential for antimicrobial applications, electrosprayed water generally operates under an electrical discharge condition, which can generate ozone. The inhalation of ozone is known to cause damage to the respiratory system of humans. Another technical barrier for electrospraying is the low flow rate problem. Since electrospraying exhibits the dependence of droplet size on the flow rate, there is a limit for the amount of water microdroplets a single nozzle can produce.
With this in mind, the research team developed a dielectric polymer micro-nozzle array to perform the multiplexed electrospraying of water without electrical discharge. The polymer micro-nozzle array was fabricated using the MEMS (Micro Electro-Mechanical System) process. According to the research team, the nozzle can carry five to 19 micro-nozzles depending on the required application.
The high aspect ratio of the micro-nozzle and an in-plane extractor were proposed to concentrate the electric field at the tip of the micro-nozzle, which prevents the electrical discharge caused by the high surface tension of water. A micro-pillar array with a hydrophobic coating around the micro-nozzle was also proposed to prevent the wetting of the micro-nozzle array.
The polymer micro-nozzle array performed in steady cone jet mode without electrical discharge as confirmed by high-speed imaging and nanosecond pulsed imaging. The water microdroplets were measured to be in the range of six to 10 μm and displayed an antimicrobial effect on Escherichia coli and Staphylococcus aureus.
Professor Lee said, “We believe that this research can be applied to air conditioning products in areas that require antimicrobial and humidifying functions.”
Publication:
Jeong, J. H., et al. (2020) Polymer micro-atomizer for water electrospray in the cone jet mode. Polymer. Vol. No. 194, 122405. Available online at https://doi.org/10.1016/j.polymer.2020.122405
Profile: Seung Seob Lee, Ph.D.
sslee97@kaist.ac.kr
http://mmst.kaist.ac.kr/
Professor
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Ji-hun Jeong, Ph.D.
jiuni6022@kaist.ac.kr
Postdoctoral researcher
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
(END)
2020.12.21 View 10833 -
Researchers Report Longest-lived Aqueous Flow Batteries
New technology to overcome the life limit of next-generation water-cell batteries
A research team led by Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering has developed water-based zinc/bromine redox flow batteries (ZBBs) with the best life expectancy among all the redox flow batteries reported by identifying and solving the deterioration issue with zinc electrodes.
Professor Kim, head of the Advanced Battery Center at KAIST's Nano-fusion Research Institute, said, "We presented a new technology to overcome the life limit of next-generation water-cell batteries. Not only is it cheaper than conventional lithium-ion batteries, but it can contribute to the expansion of renewable energy and the safe supply of energy storage systems that can run with more than 80 percent energy efficiency."
ZBBs were found to have stable life spans of more than 5,000 cycles, even at a high current density of 100 mA/cm2. It was also confirmed that it represented the highest output and life expectancy compared to Redox flow batteries (RFBs) reported worldwide, which use other redox couples such as zinc-bromine, zinc-iodine, zinc-iron, and vanadium.
Recently, more attention has been focused on energy storage system (ESS) that can improve energy utilization efficiency by storing new and late-night power in large quantities and supplying it to the grid if necessary to supplement the intermittent nature of renewable energy and meet peak power demand.
However, lithium-ion batteries (LIBs), which are currently the core technology of ESSs, have been criticized for not being suitable for ESSs, which store large amounts of electricity due to their inherent risk of ignition and fire. In fact, a total of 33 cases of ESSs using LIBs in Korea had fire accidents, and 35% of all ESS facilities were shut down. This is estimated to have resulted in more than 700 billion won in losses.
As a result, water-based RFBs have drawn great attention. In particular, ZBBs that use ultra-low-cost bromide (ZnBr2) as an active material have been developed for ESSs since the 1970s, with their advantages of high cell voltage, high energy density, and low price compared to other RFBs. Until now, however, the commercialization of ZBBs has been delayed due to the short life span caused by the zinc electrodes. In particular, the uneven "dendrite" growth behavior of zinc metals during the charging and discharging process leads to internal short circuits in the battery which shorten its life.
The research team noted that self-aggregation occurs through the surface diffusion of zinc nuclei on the carbon electrode surface with low surface energy, and determined that self-aggregation was the main cause of zinc dendrite formation through quantum mechanics-based computer simulations and transmission electron microscopy. Furthermore, it was found that the surface diffusion of the zinc nuclei was inhibited in certain carbon fault structures so that dendrites were not produced.
Single vacancy defect, where one carbon atom is removed, exchanges zinc nuclei and electrons, and is strongly coupled, thus inhibiting surface diffusion and enabling uniform nuclear production/growth. The research team applied carbon electrodes with high density fault structure to ZBBs, achieving life characteristics of more than 5,000 cycles at a high charge current density (100 mA/cm2), which is 30 times that of LIBs.
This ESS technology, which can supply eco-friendly electric energy such as renewable energy to the private sector through technology that can drive safe and cheap redox flow batteries for long life, is expected to draw attention once again.
Publication:
Ju-Hyuk Lee, Riyul Kim, Soohyun Kim, Jiyun Heo, Hyeokjin Kwon, Jung Hoon Yang, and Hee-Tak Kim. 2020. Dendrite-free Zn electrodeposition triggered by interatomic orbital hybridization of Zn and single vacancy carbon defects for aqueous Zn-based flow batteries. Energy and Environmental Science, 2020, 13, 2839-2848.
Link to download the full-text paper:http://xlink.rsc.org/?DOI=D0EE00723D
Profile: Prof. Hee-Tak Kimheetak.kim@kaist.ac.krhttp://eed.kaist.ac.krAssociate ProfessorDepartment of Chemical & Biomolecular EngineeringKAIST
2020.12.16 View 10995 -
Mystery Solved with Math: Cytoplasmic Traffic Jam Disrupts Sleep-Wake Cycles
KAIST mathematicians and their collaborators at Florida State University have identified the principle of how aging and diseases like dementia and obesity cause sleep disorders. A combination of mathematical modelling and experiments demonstrated that the cytoplasmic congestion caused by aging, dementia, and/or obesity disrupts the circadian rhythms in the human body and leads to irregular sleep-wake cycles. This finding suggests new treatment strategies for addressing unstable sleep-wake cycles.
Human bodies adjust sleep schedules in accordance with the ‘circadian rhythms’, which are regulated by our time keeping system, the ‘circadian clock’. This clock tells our body when to rest by generating the 24-hour rhythms of a protein called PERIOD (PER) (See Figure 1).
The amount of the PER protein increases for half of the day and then decreases for the remaining half. The principle is that the PER protein accumulating in the cytoplasm for several hours enters the cell nucleus all at once, hindering the transcription of PER genes and thereby reducing the amount of PER.
However, it has remained a mystery how thousands of PER molecules can simultaneously enter into the nucleus in a complex cell environment where a variety of materials co-exist and can interfere with the motion of PER. This would be like finding a way for thousands of employees from all over New York City to enter an office building at the same time every day.
A group of researchers led by Professor Jae Kyoung Kim from the KAIST Department of Mathematical Sciences solved the mystery by developing a spatiotemporal and probabilistic model that describes the motion of PER molecules in a cell environment.
This study was conducted in collaboration with Professor Choogon Lee’s group from Florida State University, where the experiments were carried out, and the results were published in the Proceedings of the National Academy of Sciences (PNAS) last month.
The joint research team’s spatial stochastic model (See Figure 2) described the motion of PER molecules in cells and demonstrated that the PER molecule should be sufficiently condensed around the cell nucleus to be phosphorylated simultaneously and enter the nucleus together (See Figure 3 Left). Thanks to this phosphorylation synchronization switch, thousands of PER molecules can enter the nucleus at the same time every day and maintain stable circadian rhythms.
However, when aging and/or diseases including dementia and obesity cause the cytoplasm to become congested with increased cytoplasmic obstacles such as protein aggregates and fat vacuoles, it hinders the timely condensation of PER molecules around the cell nucleus (See Figure 3 Right). As a result, the phosphorylation synchronization switch does not work and PER proteins enter into the nucleus at irregular times, making the circadian rhythms and sleep-wake cycles unstable, the study revealed.
Professor Kim said, “As a mathematician, I am excited to help enable the advancement of new treatment strategies that can improve the lives of so many patients who suffer from irregular sleep-wake cycles. Taking these findings as an opportunity, I hope to see more active interchanges of ideas and collaboration between mathematical and biological sciences.”
This work was supported by the National Institutes of Health and the National Science Foundation in the US, and the International Human Frontiers Science Program Organization and the National Research Foundation of Korea.
Publication:
Beesley, S. and Kim, D. W, et al. (2020) Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis. Proceedings of the National Academy of Sciences (PNAS), Vol. 117, No. 45, 28402-28411. Available online at https://doi.org/10.1073/pnas.2003524117
Profile:
Jae Kyoung Kim, Ph.D.
Associate Professor
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
@umichkim on Twitter
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile:
Choogon Lee, Ph.D.
Associate Professor
clee@neuro.fsu.edu
https://med.fsu.edu/biosci/lee-lab
Department of Biomedical Sciences
Florida State University
Florida, USA
(END)
2020.12.11 View 8322 -
A Comprehensive Review of Biosynthesis of Inorganic Nanomaterials Using Microorganisms and Bacteriophages
There are diverse methods for producing numerous inorganic nanomaterials involving many experimental variables. Among the numerous possible matches, finding the best pair for synthesizing in an environmentally friendly way has been a longstanding challenge for researchers and industries.
A KAIST bioprocess engineering research team led by Distinguished Professor Sang Yup Lee conducted a summary of 146 biosynthesized single and multi-element inorganic nanomaterials covering 55 elements in the periodic table synthesized using wild-type and genetically engineered microorganisms. Their research highlights the diverse applications of biogenic nanomaterials and gives strategies for improving the biosynthesis of nanomaterials in terms of their producibility, crystallinity, size, and shape.
The research team described a 10-step flow chart for developing the biosynthesis of inorganic nanomaterials using microorganisms and bacteriophages. The research was published at Nature Review Chemistry as a cover and hero paper on December 3.
“We suggest general strategies for microbial nanomaterial biosynthesis via a step-by-step flow chart and give our perspectives on the future of nanomaterial biosynthesis and applications. This flow chart will serve as a general guide for those wishing to prepare biosynthetic inorganic nanomaterials using microbial cells,” explained Dr.Yoojin Choi, a co-author of this research.
Most inorganic nanomaterials are produced using physical and chemical methods and biological synthesis has been gaining more and more attention. However, conventional synthesis processes have drawbacks in terms of high energy consumption and non-environmentally friendly processes. Meanwhile, microorganisms such as microalgae, yeasts, fungi, bacteria, and even viruses can be utilized as biofactories to produce single and multi-element inorganic nanomaterials under mild conditions.
After conducting a massive survey, the research team summed up that the development of genetically engineered microorganisms with increased inorganic-ion-binding affinity, inorganic-ion-reduction ability, and nanomaterial biosynthetic efficiency has enabled the synthesis of many inorganic nanomaterials.
Among the strategies, the team introduced their analysis of a Pourbaix diagram for controlling the size and morphology of a product. The research team said this Pourbaix diagram analysis can be widely employed for biosynthesizing new nanomaterials with industrial applications.Professor Sang Yup Lee added, “This research provides extensive information and perspectives on the biosynthesis of diverse inorganic nanomaterials using microorganisms and bacteriophages and their applications. We expect that biosynthetic inorganic nanomaterials will find more diverse and innovative applications across diverse fields of science and technology.”
Dr. Choi started this research in 2018 and her interview about completing this extensive research was featured in an article at Nature Career article on December 4.
-ProfileDistinguished Professor Sang Yup Lee leesy@kaist.ac.krMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.krDepartment of Chemical and Biomolecular EngineeringKAIST
2020.12.07 View 8872 -
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 10944 -
Feel the Force with ElaStick
ElaStick, a handheld variable stiffness display, renders the dynamic haptic response of a flexible object
Haptic controllers play an important role in providing rich and immersive virtual reality experiences. Professor Andrea Bianchi’s team in the Department of Industrial Design recreated the haptic response of flexible objects made of different materials and with different shapes by changing the stiffness of a custom-controller – ElaStick.
ElaStick is a portable hand-held force-feedback controller that is capable of rendering the illusion of how flexible and deformable objects feel when held in the hand. This VR haptic controller can change its stiffness in two directions independently and continuously. Since providing haptic feedback enhances the VR experience, researchers have suggested numerous approaches for rendering the physical properties of virtual objects - such as weights, the movement of mass, impacts, and damped oscillations.
The research team designed a new mechanism based on a quaternion joint and four variable-stiffness tendons. The quaternion joint is a two-DoF bending joint that enables ElaStick to bend and oscillate in any direction using a pair of tendons with varying stiffness. In fact, each tendon around the joint is made of a series of elastic rubber bands and inelastic fishing lines and can vary its stiffness by changing the proportion of the two materials. Thanks to these structures, each pair of tendons can behave independently, controlling the anisotropic characteristics of the entire device.
“The main challenge was to implement the mechanism to control the stiffness while maintaining independence between deformations in two perpendicular directions,” said Professor Bianchi.
The research team successfully measured the relative threshold of human perception on the stiffness of a handheld object. The results showed that the just-noticeable difference (JND) of human perception of stiffness is at most about 30% of the change from the initial value. It also found that appropriate haptic responses significantly enhance the quality of the VR experience. The research team surveyed the perceived realism, immersion, and enjoyment of participants after they played with various flexible objects in VR.
“It is meaningful that the haptic feedback of a flexible object was mechanically reproduced and its effectiveness in VR was proven. ElaStick has succeeded in implementing a novel mechanism to recreate the dynamic response of flexible objects that mimic real ones, suggesting a new category of haptic feedback that can be provided in VR,” explained Professor Bianchi.
The team plans to extend the ElaStick’s applications, from being used merely as a game controller to driving simulations, medical training, and many other digital contexts. This research, led by MS candidate Neung Ryu, won the Best Paper Award at the ACM UIST 2020 (the ACM Symposium on User Interface Software & Technology) last month.
-ProfileProfessor Andrea BianchiMakinteract.kaist.ac.krDepartment of Industrial DesignKAIST
2020.11.23 View 5457 -
Researchers Control Multiple Wavelengths of Light from a Single Source
KAIST researchers have synthesized a collection of nanoparticles, known as carbon dots, capable of emitting multiple wavelengths of light from a single particle. Additionally, the team discovered that the dispersion of the carbon dots, or the interparticle distance between each dot, influences the properties of the light the carbon dots emit. The discovery will allow researchers to understand how to control these carbon dots and create new, environmentally responsible displays, lighting, and sensing technology.
Research into nanoparticles capable of emitting light, such as quantum dots, has been an active area of interest for the last decade and a half. These particles, or phosphors, are nanoparticles made out of various materials that are capable of emitting light at specific wavelengths by leveraging quantum mechanical properties of the materials. This provides new ways to develop lighting and display solutions as well as more precise detection and sensing in instruments.
As technology becomes smaller and more sophisticated, the usage of fluorescent nanoparticles has seen a dramatic increase in many applications due to the purity of the colors emitting from the dots as well as their tunability to meet desired optical properties.
Carbon dots, a type of fluorescent nanoparticles, have seen an increase in interest from researchers as a candidate to replace non-carbon dots, the construction of which requires heavy metals that are toxic to the environment. Since they are made up of mostly carbon, the low toxicity is an extremely attractive quality when coupled with the tunability of their inherent optical properties.
Another striking feature of carbon dots is their capability to emit multiple wavelengths of light from a single nanoparticle. This multi-wavelength emission can be stimulated under a single excitation source, enabling the simple and robust generation of white light from a single particle by emitting multiple wavelengths simultaneously.
Carbon dots also exhibit a concentration-dependent photoluminescence. In other words, the distance between individual carbon dots affects the light that the carbon dots subsequently emit under an excitation source. These combined properties make carbon dots a unique source that will result in extremely accurate detection and sensing.
This concentration-dependency, however, had not been fully understood. In order to fully utilize the capabilities of carbon dots, the mechanisms that govern the seemingly variable optical properties must first be uncovered. It was previously theorized that the concentration-dependency of carbon dots was due to a hydrogen bonding effect.
Now, a KAIST research team, led by Professor Do Hyun Kim of the Department of Chemical and Biomolecular Engineering has posited and demonstrated that the dual-color-emissiveness is instead due to the interparticle distances between each carbon dot. This study was made available online in June 2020 ahead of final publication in the 36th Issue of Physical Chemistry Chemical Physics on September 28, 2020.
First author of the paper, PhD candidate Hyo Jeong Yoo, along with Professor Kim and researcher Byeong Eun Kwak, examined how the relative light intensity of the red and blue colors changed when varying the interparticle distances, or concentration, of the carbon dots. They found that as the concentration was adjusted, the light emitted from the carbon dots would transform. By varying the concentration, the team was able to control the relative intensity of the colors, as well as emit them simultaneously to generate a white light from a single source (See Figure).
“The concentration-dependence of the photoluminescence of carbon dots on the change of the emissive origins for different interparticle distances has been overlooked in previous research. With the analysis of the dual-color-emission phenomenon of carbon dots, we believe that this result may provide a new perspective to investigate their photoluminescence mechanism,” Yoo explained.
The newly analyzed ability to control the photoluminescence of carbon dots will likely be heavily utilized in the continued development of solid-state lighting applications and sensing.
Publication:
Yoo, H. J., Kwak, B. E., and Kim. D. H. (2020) Interparticle distance as a key factor for controlling the dual-emission properties of carbon dots. Physical Chemistry Chemical Physics, Issue 36, Pages 20227-20237. Available online at https://doi.org/10.1039/d0cp02120b
Profile:
Do Hyun Kim, Sc.D.
Professor
dokim@kaist.ac.kr
http://procal.kaist.ac.kr/
Process Analysis Laboratory
Department of Chemical and Biomolecular Engineering
https://www.kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea
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2020.11.23 View 9230 -
Engineered C. glutamicum Strain Capable of Producing High-Level Glutaric Acid from Glucose
An engineered C. glutamicum strain that can produce the world’s highest titer of glutaric acid was developed by employing systems metabolic engineering strategies
A metabolic engineering research group at KAIST has developed an engineered Corynebacterium glutamicum strain capable of producing high-level glutaric acid without byproducts from glucose. This new strategy will be useful for developing engineered micro-organisms for the bio-based production of value-added chemicals.
Glutaric acid, also known as pentanedioic acid, is a carboxylic acid that is widely used for various applications including the production of polyesters, polyamides, polyurethanes, glutaric anhydride, 1,5-pentanediol, and 5-hydroxyvaleric acid. Glutaric acid has been produced using various petroleum-based chemical methods, relying on non-renewable and toxic starting materials. Thus, various approaches have been taken to biologically produce glutaric acid from renewable resources. Previously, the development of the first glutaric acid producing Escherichia coli by introducing Pseudomonas putida genes was reported by a research group from KAIST, but the titer was low. Glutaric acid production by metabolically engineered Corynebacterium glutamicum has also been reported in several studies, but further improvements in glutaric acid production seemed possible since C. glutamicum has the capability of producing more than 130 g/L of L-lysine.
A research group comprised of Taehee Han, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. Their research paper “Glutaric acid production by systems metabolic engineering of an L-lysine-overproducing Corynebacterium glutamicum” was published online in PNAS on November 16, 2020.
This research reports the development of a metabolically engineered C. glutamicum strain capable of efficiently producing glutaric acid, starting from an L-lysine overproducer. The following novel strategies and approaches to achieve high-level glutaric acid production were employed. First, metabolic pathways in C. glutamicum were reconstituted for glutaric acid production by introducing P. putida genes. Then, multi-omics analyses including genome, transcriptome, and fluxome were conducted to understand the phenotype of the L-lysine overproducer strain. In addition to systematic understanding of the host strain, gene manipulation targets were predicted by omics analyses and applied for engineering C. glutamicum, which resulted in the development of an engineered strain capable of efficiently producing glutaric acid. Furthermore, the new glutaric acid exporter was discovered for the first time, which was used to further increase glutaric acid production through enhancing product excretion. Last but not least, culture conditions were optimized for high-level glutaric acid production. As a result, the final engineered strain was able to produce 105.3 g/L glutaric acid, the highest titer ever reported, in 69 hours by fed-batch fermentation.
Professor Sang Yup Lee said, “It is meaningful that we were able to develop a highly efficient glutaric acid producer capable of producing glutaric acid at the world’s highest titer without any byproducts from renewable carbon sources. This will further accelerate the bio-based production of valuable chemicals in pharmaceutical/medical/chemical industries.” This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation and funded by the Ministry of Science and ICT.
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
2020.11.17 View 6194 -
Drawing the Line to Answer Art’s Big Questions
- KAIST scientists show how statistical physics can reveal art trends across time and culture. -
Algorithms have shown that the compositional structure of Western landscape paintings changed “suspiciously” smoothly between 1500 and 2000 AD, potentially indicating a selection bias by art curators or in art historical literature, physicists from the Korea Advanced Institute of Science and Technology (KAIST) and colleagues report in the Proceedings of the National Academy of Sciences (PNAS).
KAIST statistical physicist Hawoong Jeong worked with statisticians, digital analysts and art historians in Korea, Estonia and the US to clarify whether computer algorithms could help resolve long-standing questions about design principles used in landscape paintings, such as the placement of the horizon and other primary features.
“A foundational question among art historians is whether artwork contains organizing principles that transcend culture and time and, if yes, how these principles evolved over time,” explains Jeong. “We developed an information-theoretic approach that can capture compositional proportion in landscape paintings and found that the preferred compositional proportion systematically evolved over time.”
Digital versions of almost 15,000 canonical landscape paintings from the Western renaissance in the 1500s to the more recent contemporary art period were run through a computer algorithm. The algorithm progressively divides artwork into horizontal and vertical lines depending on the amount of information in each subsequent partition. It allows scientists to evaluate how artists and various art styles compose landscape artwork, in terms of placement of a piece’s most important components, in addition to how high or low the landscape’s horizon is placed.
The scientists started by analysing the first two partitioning lines identified by the algorithm in the paintings and found they could be categorized into four groups: an initial horizontal line followed by a second horizontal line (H-H); an initial horizontal line followed by a second vertical line (H-V); a vertical followed by horizontal line (V-H); or a vertical followed by a vertical line (V-V) (see image 1 and 2). They then looked at the categorizations over time.
They found that before the mid-nineteenth century, H-V was the dominant composition type, followed by H-H, V-H, and V-V. The mid-nineteenth century then brought change, with the H-V composition style decreasing in popularity with a rise in the H-H composition style. The other two styles remained relatively stable.
The scientists also looked at how the horizon line, which separates sky from land, changed over time. In the 16th century, the dominant horizon line of the painting was above the middle of the canvas, but it gradually descended to the lower middle of the canvas by the 17th century, where it remained until the mid-nineteenth century. After that, the horizon line began gradually rising again.
Interestingly, the algorithm showed that these findings were similar across cultures and artistic periods, even through periods dominated by a diversity in art styles. This similarity may well be a function, then, of a bias in the dataset.
“In recent decades, art historians have prioritized the argument that there is great diversity in the evolution of artistic expression rather than offering a relatively smoother consensus story in Western art,” Jeong says. “This study serves as a reminder that the available large-scale datasets might be perpetuating severe biases.”
The scientists next aim to broaden their analyses to include more diverse artwork, as this particular dataset was ultimately Western and male biased. Future analyses should also consider diagonal compositions in paintings, they say.
This work was supported by the National Research Foundation (NRF) of Korea.
Publication:
Lee, B, et al. (2020) Dissecting landscape art history with information theory. Proceedings of the National Academy of Sciences (PNAS), Vol. 117, No. 43, 26580-26590. Available online at https://doi.org/10.1073/pnas.2011927117
Profile:
Hawoong Jeong, Ph.D.
Professor
hjeong@kaist.ac.kr
https://www.kaist.ac.kr
Department of Physics
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
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2020.11.13 View 9461