Nature+Communications
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Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease
Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week.
Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear.
Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing.
The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases.
The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD.
Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins.
“Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee.
The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease.
(Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.)
(Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.)
(Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
2019.07.19 View 34139 -
Novel Via-Hole-Less Multilevel Metal Interconnection Methods
Forming reliable multi-level metal interconnections is a key technology for integrating devices into organic integrated circuits (ICs). The conventional approach, called “via-hole,” locally removes the insulator and utilizes metal interconnects through the holes. Due to the high sensitivity of organic materials to chemical solvents, heat, and photo-radiation used in conventional “via-hole” methods, alternative printing methods or laser drilling methods have been developed. However, finding a reliable and practical metal interconnection for organic ICs is still challenging.
The research team of KAIST Professor Sung Gap Im and Postech Professor Kim Jae-Joon reported a new interconnection method that does not require via-hole formation, “via-hole-less metal interconnection,” in Nature Communications on June 3.
Metal electrodes in different layers can be isolated from each other by patterned dielectric layers, where they then can be interconnected to others in the open area where the dielectric layer is not present. See the images below. Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below.
Vapor phase deposition and in-situ patterning of dielectric layer using iCVD (initiated chemical vapor deposition), used in the “via-hole-less” method, ensure a damage-free process for organic semiconductor materials and result in outstanding performance of the organic devices as multilevel metal interconnects are reliably formed. The team successfully demonstrated three-dimensional (3D) stacking of five organic transistors and integrated circuits using the proposed via-hole-less interconnect method. See the image below.
Professor Kim explained, “Our proposed via-hole-less interconnect method using a selectively patterned dielectric overcomes the limitations of the previous time-consuming, one-by-one via-hole formation process and provides reliable methods for creating metal interconnects in organic ICs. We expect the via-hole-less scheme to bring advances to organic IC technology.”
2019.06.18 View 42321 -
Fast-Charging Lithium-Oxygen Batteries
(Professor Hye Ryung Byon)
KAIST researchers have paved the way for fast-charging lithium-oxygen batteries.
Professor Hye Ryung Byon from the Department of Chemistry and Professor Yousung Jung from the Graduate School of EEWS led a joint research team to develop lithium-oxygen batteries exhibiting 80% round-trip efficiency even at high charging rates, solving the problem of existing lithium-oxygen batteries which generally showed drastically lower efficiencies when the charge current rate was increased.
This study exploits the size and shape lithium peroxide, a discharge product, which is known to cause the very problems mentioned above. In doing so, the researchers have lowered the overpotential, which is the difference between the thermodynamic reversible potential and the measured potential, and simultaneously improved battery efficiency. Of particular interest is the fact that these high-performance lithium-oxygen batteries can be realized without costly catalysts.
One remarkable property of lithium-oxygen batteries is that they can accommodate three to five times the energy density of lithium-ion batteries commonly used today. Therefore, lithium-oxygen batteries would render longer driving distance to electric vehicles or drones, which operate on the continued use of electrical power.
However, their weakness lies in that, during charge, the lithium peroxide remains undecomposed at low overpotential, resulting in eventually compromising the battery’s overall performance. This is due to the poor ionic and electrical conductivity of lithium peroxide.
To tackle this issue, the researchers could form one-dimensional amorphous lithium peroxide nanostructures through the use of a mesoporous carbon electrode, CMK-3. When compared against non-mesoporous electrodes, CMK-3 showed exceptionally lower overpotential, thereby enhancing the round-trip efficiency of lithium-oxygen batteries.
The amorphous lithium peroxide produced along the electrode has a small volume and a large surface area contacting electrolyte solution, which is presumably endowed with high conductivity to speed up the charging of the lithium-oxygen batteries.
This research underpins the feasibility of overcoming the fundamental limitations of lithium-oxygen batteries even without the addition of expensive catalytic materials, but rather by the re-configuration of the size and shape of the lithium peroxide.
The findings of this research were published in Nature Communications on February 14.
Figure 1. Transmission electron microscopy (TEM) images
Figure 2. Galvanostatic rate capability
Figure 3. Density functional calculation and Bader charge analysis
2018.05.30 View 8853 -
Undergrad's Paper Chosen as the Cover Article in Soft Matter
(from left: Research Professor KyuHan Kim and Undergrad Student Subeen Kim)
A KAIST undergraduate student, Subeen Kim, had his paper chosen as the cover article in an international journal during his senior year.
There have been an increasing number of undergraduate students who were published as the first author because the KAIST Undergraduate Research Participation program allows more active research participation by undergraduate students.
Through URP, Kim successfully published his paper in the internationally-renowned journal, Soft Matter, which is published by the Royal Society of Chemistry, and it was chosen as the cover article of that journal in February 2018.
This publication means a lot to him because he designed the cover image himself, based on his imagination and observations.
His research is about controllable one-step double emulsion formation. Double emulsion is a system in which dispersed droplets contain additional immiscible liquid droplets.
Having great retention ability, double emulsion has been used in various applications in the food industry, in cosmetics, and for drug delivery. Nevertheless, two-step emulsification is a conventional approach to produce double emulsions that typically leads to partial destabilization of the emulsion formed during the initial stage. Hence, it does not ensure the stability of a double emulsion. On the other hand, a microfluidic approach with various flow-focusing techniques has been developed, but it has low production efficiency and thus limited industrial applications.
Kim’s results came from the process of phase inversion to solve this problem. He identified the instant formation of double emulsions during the process of phase inversion. Based on this finding, he proposed criteria to achieve high stability of double emulsion.
Through constant research, he developed a quite general method using a combination of an oil soluble poly methyl methacrylate (PMMA) and hydrophobic silica nanoparticle (HDK H18). This new method enables one-step and stable production of double emersions in a stable manner. It also allows control of the number and the volume of inner oil droplets inside the outer water droplets by adjusting PMMA and HDK H18.
Kim enrolled at KAIST as a KAIST Presidential Fellowship and Presidential Science Scholarship in 2014. While studying both chemical and biomolecular engineering and chemistry he has been developing his hypothesis and conducting research.
He was able to begin conducting research because he has taken part in URP projects twice. In his sophomore year, he studied the formation of high internal phase double emulsions. After one year, he conducted research to produce superabsorbent resins, which are the base material for diapers, by using colloid particles. Using partial research outcomes, he published his paper in Nature Communications as a second author.
Kim said, “Double majoring the chemical and biomolecular engineering and chemistry has helped me producing this outcome. I hope that this research contributes to commercializing double emulsions. I will continue to identify accurate principles to produce chemicals that can be controlled exquisitely.”
Figure 1. The cover article of Soft Matter
2018.05.03 View 9219 -
One-Step Production of Aromatic Polyesters by E. coli Strains
KAIST systems metabolic engineers defined a novel strategy for microbial aromatic polyesters production fused with synthetic biology from renewable biomass. The team of Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering produced aromatic polyesters from Escherichia coli (E. coli) strains by applying microbial fermentation, employing direct microbial fermentation from renewable feedstock carbohydrates.
This is the first report to determine a platform strain of engineered E. coli capable of producing environmentally friendly aromatic polyesters. This engineered E. coli strain, if desired, has the potential to be used as a platform strain capable of producing various high-valued aromatic polyesters from renewable biomass. This research was published in Nature Communications on January 8.
Conventionally, aromatic polyesters boast solid strength and heat stability so that there has been a great deal of interest in fermentative production of aromatic polyesters from renewable non-food biomass, but without success.
However, aromatic polyesters are only made by feeding the cells with corresponding aromatic monomers as substrates, and have not been produced by direct fermentation from renewable feedstock carbohydrates such as glucose.
To address this issue, the team prescribed the detailed procedure for aromatic polyester production through identifying CoA-transferase that activates phenylalkanoates into their corresponding CoA derivatives. In this process, researchers employed metabolic engineering of E. coli to produce phenylalkanoates from glucose based on genome-scale metabolic flux analysis. In particular, the KAIST team made a modulation of gene expression to produce various aromatic polyesters having different monomer fractions.
The research team successfully produced aromatic polyesters, a non-natural polymer using the strategy that combines systems metabolic engineering and synthetic biology. They succeeded in biosynthesis of various kinds of aromatic polyesters through the system, thus proving the technical excellence of the environmentally friendly biosynthetic system of this research. Furthermore, his team also proved the potential of expanding the range of aromatic polyesters from renewable resources, which is expected to play an important role in the bio-plastic industry.
Professor Lee said, “An eco-friendly and sustainable chemical industry is the key global agenda every nation faces. We are making a research focus to a biochemical industry free from petroleum dependence, and conducting diverse research activities to address the issue. This novel technology we are presenting will serve as an opportunity to advance the biochemical industry moving forward.”
This work was supported by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) and also by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation of Korea.
Figure: Biosynthesis of aromatic polyesters by metabolically engineered E. coli.This schematic diagram shows the overall conceptualization of how metabolically engineered E. coli produced aromatic polyesters from glucose.
2018.01.09 View 6771 -
Expanding the Genetic Code of Mus Musculus
Professor Hee-Sung Park of the Department of Chemistry, who garnered attention for his novel strategy of installing authentic post-translational modifications into recombinant proteins, expanded his research portfolio to another level. Professor Park’s team was the first to report the generation of a mouse strain with an expanded genetic code, allowing site-specific incorporation of unnatural amino acids.
Professor Park published the research on the new chemical biology method for achieving selective chemical modifications in proteins in Science last September. The research team, this time in collaboration with Professor Chan Bae Park of the Department of Physiology at the Ajou University School of Medicine, demonstrated temporal and spatial control of protein acetylation in various organs of the transgenic mouse using a recombinant green fluorescent protein as a model protein. This research was published in the online edition of Nature Communications on February 21.
This approach enables the rapid onset of position-specific acetylation of a target protein at any developmental stage, facilitating temporal and spatial control of protein acetylation in various organs of the transgenic mouse. Such temporal and spatial control of protein acetylation will be of prime importance for investigating many essential biological processes and human diseases at the tissue and organism level.
Almost all human proteins, the products of about 25,000 genes, are known to undergo various post-translational modifications during and after synthesis. Post-translation modifications regulate the function of cellular proteins, playing a key role in many essential processes such as delivering signals and body growth. However, the unusual protein modifications, aroused from genetic and/or environmental factors, trigger severe diseases including cancer, dementia, and diabetes.
The team inserted transgenes into the mouse genome to allocate the site-specific addition of unnatural amino acids. The researchers inserted a modified version of lysine into the house mice, which allowed for the control of the acetylation. They used recombinant green fluorescent proteins from transgenic house mice as models for control of the acetylation.
The team was also able to regulate the acetylation of specific temporal and spatial frames in the mice, restraining the abnormality in proteins to certain organs such as the liver and kidneys. The research team said the strategy will provide a powerful tool for systematic in vivo study of cellular proteins in the most commonly used mammalian model organisms for human physiology and disease. Professor Park said, “This method can be easily extended to generate a wide range of custom-made transgenic mouse strains for further investigating diverse proteins of interest.” He added, “This method can be further extended to generate a wide range of custom-made transgenic mouse strains, opening a new paradigm for investigating anti-cancer and cerebral disease treatments.
This work was supported by grants from KAIST Systems Healthcare and the Medicinal Bioconvergence Research Center and the Intelligent Synthetic Biology Center of the Global Frontier Project funded by the Ministry of Science, ICT & Future Planning and the Ministry of Food and Drug Safety.
(Figure:Temporal and spatial control of in vivo protein acetylation)
(a) Temporal expression of acetylated GFPuv in the AcK-GFPamber mouse. The expression of GFPuv in skeletal muscle, liver, and lung tissues was detected only in the AcK-injected mouse. Scale bar, 200 µm. (b) Western blotting of anti-FLAG-immunoprecipitated proteins from tissues of the AcK-GFPamber mouse. Acetylated GFPuv was produced after AcK injection. (c) Spatial expression of acetylated GFPuv in the AcK-GFPamber mouse. Acetylated GFPuv was observed only in skeletal muscle when AcK was directly delivered to the tissues. Sacle bar, 200 µm.
2017.03.27 View 8433 -
Adsorbent That Can Selectively Remove Water Contaminants
Professor Cafer T. Yavuz and his team at the Graduate School of Energy, Environment, Water, and Sustainability (EEWS) have developed an adsorbent that can selectively capture soluble organic contaminants in water.
This water treatment adsorbent is a fluorine-based nanoporous polymer that can selectively remove water-soluble micromolecules. It has the added advantage of being cheap and easily synthesized, while also being renewable.
The results of this research have been published online in Nature Communication on November 10, 2016. The research paper is titled “Charge-specific Size-dependent Separation of Water-soluble Organic Molecules by Fluorinated Nanoporous Networks.” (DOI: 10.1038/ncomms13377)
Water pollution is accelerating as a result of global industrial development and warming. As new materials are produced and applied in the agricultural and industrial sectors, the types of contaminants expelled as sewage and waste water are also becoming diverse.
Chemicals such as dyes and pesticides can be especially harmful because they are made up of small and highly soluble organic particles that cannot be completely removed during the water treatment process, ultimately ending up in our drinking water.
The current conventional water treatment systems utilize processes such as activated carbon, ozonolysis, and reverse osmosis membrane. These processes, however, are designed to remove larger organic molecules with lower solubility, thus removal of very small molecules with high solubility is difficult. In addition, these micromolecules tend to be charged, therefore are less easily separated in aqueous form.
The research team aimed to remove these small molecules using a new adsorbent technology.
In order to remove aqueous organic molecular contaminants, the team needed an adsorbent that can adsorb micro-sized molecules. It also needed to introduce a chemical function that would allow it to selectively adsorb molecules, and lastly, the adsorbent needed to be structurally stable as it would be used underwater.
The team subsequently developed an adsorbent of fluorine-based porous organic polymer that met all the conditions listed above. By controlling the size of the pores, this adsorbent is able to selectively adsorb aqueous micromolecules of less than 1-2 nm in size.
In addition, in order to separate specific contaminants, there should be a chemical functionality, such as the ability to strongly interact with the target material. Fluorine, the most electronegative atom, interacts strongly with charged soluble organic molecules.
The research team incorporated fluorine into an adsorbent, enabling it to separate charged organic molecules up to 8 times faster than neutral molecules.
The adsorbent developed by Professor Yavuz’s team has wide industrial applications. It can be used in batch-adsorption tests, as well as in column separation for size- and charge-specific adsorption.
Professor Yavuz stated that “the charge-selective properties displayed by fluorine has the potential to be applied in desalination or water treatment processes using membranes."
This paper was first-authored by Dr. Jeehye Byun, and the research was funded by KAIST’s High Risk High Return Program and the Ministry of Science, ICT and Future Planning of Korea’s Mid-Career Researcher Program, as well as its Technology Development Program to Solve Climate Change.
Figure 1. Diagram conceptualizing the process of charge- and size-specific separation by the fluorine-based porous polymer adsorbent
Figure 2. Difference in absorbance before and after using a porous fluorine polymer column to separate organic molecules
Figure 3. Adsorption properties of a fluorine polymer according to the charge and size of organic molecules
2017.01.17 View 9352 -
Making Graphene Using Laser-induced Phase Separation
IBS & KAIST researchers clarify how laser annealing technology can lead to the production of ultrathin nanomaterials
All our smart phones have shiny flat AMOLED (active-matrix organic light-emitting diode) displays. Behind each single pixel of these displays hides at least two silicon transistors which are mass-manufactured using laser annealing technology. While the traditional methods to make the transistors use temperature above 1,000°C, the laser technique reaches the same results at low temperatures even on plastic substrates (melting temperature below 300°C). Interestingly, a similar procedure can be used to generate crystals of graphene. Graphene is a strong and thin nano-material made of carbon, its electric and heat-conductive properties have attracted the attention of scientists worldwide.
Professor Keon Jae Lee of the Materials Science and Engineering Department at KAIST and his research group at the Center for Multidimensional Carbon Materials within the Institute for Basic Science (IBS), as well as Professor Sung-Yool Choi of the Electrical Engineering School at KAIST and his research team discovered graphene synthesis mechanism using laser-induced solid-state phase separation of single-crystal silicon carbide (SiC). This study, available in Nature Communications, clarifies how this laser technology can separate a complex compound (SiC) into its ultrathin elements of carbon and silicon.
Although several fundamental studies presented the effect of excimer lasers in transforming elemental materials like silicon, the laser interaction with more complex compounds like SiC has rarely been studied due to the complexity of compound phase transition and ultra-short processing time.
With high resolution microscope images and molecular dynamic simulations, scientists found that a single-pulse irradiation of xenon chloride excimer laser of 30 nanoseconds melts SiC, leading to the separation of a liquid SiC layer, a disordered carbon layer with graphitic domains (about 2.5 nm thick) on top surface and a polycrystalline silicon layer (about 5 nm) below carbon layer. Giving additional pulses causes the sublimation of the separated silicon, while the disordered carbon layer is transformed into a multilayer graphene.
"This research shows that the laser material interaction technology can be a powerful tool for the next generation of two dimensional nanomaterials," said Professor Lee.
Professor Choi added: "Using laser-induced phase separation of complex compounds, new types of two dimensional materials can be synthesized in the future."
High-resolution transmission electron microscopy shows that after just one laser pulse of 30 nanoseconds, the silicon carbide (SiC) substrate is melted and separates into a carbon and a silicon layer. More pulses cause the carbon layer to organize into graphene and the silicon to leave as gas.
Molecular dynamics simulates the graphene formation mechanism. The carbon layer on the top forms because the laser-induced liquid SiC (SiC (l)) is unstable.
(Press Release by Courtesy of the Institute for Basic Science (IBS))
2016.12.01 View 9941 -
Graphene-Based Transparent Electrodes for Highly Efficient Flexible OLEDs
A Korean research team developed an ideal electrode structure composed of graphene and layers of titanium dioxide and conducting polymers, resulting in highly flexible and efficient OLEDs.
The arrival of a thin and lightweight computer that even rolls up like a piece of paper will not be in the far distant future. Flexible organic light-emitting diodes (OLEDs), built upon a plastic substrate, have received greater attention lately for their use in next-generation displays that can be bent or rolled while still operating.
A Korean research team led by Professor Seunghyup Yoo from the School of Electrical Engineering, KAIST and Professor Tae-Woo Lee from the Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH) has developed highly flexible OLEDs with excellent efficiency by using graphene as a transparent electrode (TE) which is placed in between titanium dioxide (TiO2) and conducting polymer layers. The research results were published online on June 2, 2016 in Nature Communications.
OLEDs are stacked in several ultra-thin layers on glass, foil, or plastic substrates, in which multi-layers of organic compounds are sandwiched between two electrodes (cathode and anode). When voltage is applied across the electrodes, electrons from the cathode and holes (positive charges) from the anode draw toward each other and meet in the emissive layer. OLEDs emit light as an electron recombines with a positive hole, releasing energy in the form of a photon. One of the electrodes in OLEDs is usually transparent, and depending on which electrode is transparent, OLEDs can either emit from the top or bottom.
In conventional bottom-emission OLEDs, an anode is transparent in order for the emitted photons to exit the device through its substrate. Indium-tin-oxide (ITO) is commonly used as a transparent anode because of its high transparency, low sheet resistance, and well-established manufacturing process. However, ITO can potentially be expensive, and moreover, is brittle, being susceptible to bending-induced formation of cracks.
Graphene, a two-dimensional thin layer of carbon atoms tightly bonded together in a hexagonal honeycomb lattice, has recently emerged as an alternative to ITO. With outstanding electrical, physical, and chemical properties, its atomic thinness leading to a high degree of flexibility and transparency makes it an ideal candidate for TEs. Nonetheless, the efficiency of graphene-based OLEDs reported to date has been, at best, about the same level of ITO-based OLEDs.
As a solution, the Korean research team, which further includes Professors Sung-Yool Choi (Electrical Engineering) and Taek-Soo Kim (Mechanical Engineering) of KAIST and their students, proposed a new device architecture that can maximize the efficiency of graphene-based OLEDs. They fabricated a transparent anode in a composite structure in which a TiO2 layer with a high refractive index (high-n) and a hole-injection layer (HIL) of conducting polymers with a low refractive index (low-n) sandwich graphene electrodes. This is an optical design that induces a synergistic collaboration between the high-n and low-n layers to increase the effective reflectance of TEs. As a result, the enhancement of the optical cavity resonance is maximized. The optical cavity resonance is related to the improvement of efficiency and color gamut in OLEDs. At the same time, the loss from surface plasmon polariton (SPP), a major cause for weak photon emissions in OLEDs, is also reduced due to the presence of the low-n conducting polymers.
Under this approach, graphene-based OLEDs exhibit 40.8% of ultrahigh external quantum efficiency (EQE) and 160.3 lm/W of power efficiency, which is unprecedented in those using graphene as a TE. Furthermore, these devices remain intact and operate well even after 1,000 bending cycles at a radius of curvature as small as 2.3 mm. This is a remarkable result for OLEDs containing oxide layers such as TiO2 because oxides are typically brittle and prone to bending-induced fractures even at a relatively low strain. The research team discovered that TiO2 has a crack-deflection toughening mechanism that tends to prevent bending-induced cracks from being formed easily.
Professor Yoo said, “What’s unique and advanced about this technology, compared with previous graphene-based OLEDs, is the synergistic collaboration of high- and low-index layers that enables optical management of both resonance effect and SPP loss, leading to significant enhancement in efficiency, all with little compromise in flexibility.” He added, “Our work was the achievement of collaborative research, transcending the boundaries of different fields, through which we have often found meaningful breakthroughs.”
Professor Lee said, “We expect that our technology will pave the way to develop an OLED light source for highly flexible and wearable displays, or flexible sensors that can be attached to the human body for health monitoring, for instance.”
The research paper is entitled “Synergistic Electrode Architecture for Efficient Graphene-based Flexible Organic Light-emitting Diodes” (DOI. 10.1038/NCOMMS11791). The lead authors are Jae-Ho Lee, a Ph.D. candidate at KAIST; Tae-Hee Han, a Ph.D. researcher at POSTECH; and Min-Ho Park, a Ph.D. candidate at POSTECH.
This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) through the Center for Advanced Flexible Display (CAFDC) funded by the Ministry of Science, ICT and Future Planning (MSIP); by the Center for Advanced Soft-Electronics funded by the MSIP as a Global Frontier Project; by the Graphene Research Center Program of KAIST; and by grants from the IT R&D Program of the Ministry of Trade, Industry and Energy of Korea (MOTIE).
Figure 1: Application of Graphene-based OLEDs
This picture shows an OLED with the composite structure of TiO2/graphene/conducting polymer electrode in operation. The OLED exhibits 40.8% of ultrahigh external quantum efficiency (EQE) and 160.3 lm/W of power efficiency. The device prepared on a plastic substrate shown in the right remains intact and operates well even after 1,000 bending cycles at a radius of curvature as small as 2.3 mm.
Figure 2: Schematic Device Structure of Graphene-based OLEDs
This picture shows the new architecture to develop highly flexible OLEDs with excellent efficiency by using graphene as a transparent electrode (TE).
2016.06.07 View 12464 -
Discovery of Redox-Switch of KEenzyme Involved in N-Butanol Biosynthesis
Research teams at KAIST and Kyungpook National University (KNU) have succeeded in uncovering the redox-switch of thiolase, a key enzyme for n-butanol production in Clostridium acetobutylicum, one of the best known butanol-producing bacteria.
Biological n-butanol production was first reported by Louis Pasteur in 1861, and the bioprocess was industrialized usingClostridium acetobutylicum. The fermentation process by Clostridium strains has been known to be the most efficient one for n-butanol production. Due to growing world-wide issues such as energy security and climate change, the biological production of n-butanol has been receiving much renewed interest. This is because n-butanol possesses much better fuel characteristics compared to ethanol, such as higher energy content (29.2 MJ/L vs 19.6 MJ/L), less corrosiveness, less hygroscopy, and the ease with which it can be blended with gasoline and diesel.
In the paper published in Nature Communications, a broad-scope, online-only, and open access journal issued by the Nature Publishing Group (NPG), on September 22, 2015, Professor Kyung-Jin Kim at the School of Life Sciences, KNU, and Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering, KAIST, have proved that the redox-switch of thiolase plays a role in a regulation of metabolic flux in C. acetobutylicum by using in silico modeling and simulation tools.
The research team has redesigned thiolase with enhanced activity on the basis of the 3D structure of the wild-type enzyme. To reinforce a metabolic flux toward butanol production, the metabolic network of C. acetobutylicum strain was engineered with the redesigned enzyme. The combination of the discovery of 3D enzyme structure and systems metabolic engineering approaches resulted in increased n-butanol production in C. acetobutylicum, which allows the production of this important industrial chemical to be cost competitive.
Professors Kim and Lee said, "We have reported the 3D structure of C. acetobutylicum thiolase-a key enzyme involved in n-butanol biosynthesis, for the first time. Further study will be done to produce butanol more economically on the basis of the 3D structure of C. acetobutylicum thiolase."
This work was published online in Nature Communications on September 22, 2015.
Reference: Kim et al. "Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum," Nature Communications
This research was supported by the Technology Development Program to Solve Climate Changes from the Ministry of Education, Science and Technology (MEST), Korea, the National Research Foundation of Korea, and the Advanced Biomass Center through the Global Frontier Research Program of the MEST, Korea.
For further information, contact Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930); and Dr. Kyung-Jin Kim, Professor, KNU, Daegu, Korea (kkim@knu.ac.kr, +82-53-950-6088).
Figure 1: A redox-switch of thiolase involves in butanol biosynthesis in Clostridium acetobutylicum. Thiolase condenses two acetyl-CoA molecules for initiating four carbon flux towards butanol.
Figure 2: Thiolase catalyzes the condensation reaction of acetyl-CoA to acetoacetyl-CoA. Two catalytic cysteine residues at 88th and 378th are oxidized and formed an intermolecular disulfide bond in an oxidized status, which results in inactivation of the enzyme for n-butanol biosynthesis. The intermolecular disulfide bond is broken enabling the n-butanol biosynthesis, when the environment status is reduced.
2015.09.23 View 9798 -
Novel Photolithographic Technology Enabling 3D Control over Functional Shapes of Microstructures
Professor Shin-Hyun Kim and his research team in the Department of Chemical and Biomolecular Engineering at KAIST have developed a novel photolithographic technology enabling control over the functional shapes of micropatterns using oxygen diffusion.
The research was published online in the March 13th issue of Nature Communications and was selected as a featured image for the journal.
Photolithography is a standard optical process for transferring micropatterns on to a substrate by exposing specific regions of the photoresist layer to ultraviolet (UV) light. It is used widely throughout industries that require micropatterns, especially in the semiconductor manufacturing industry.
Conventional photolithography relied on photomasks which protected certain regions of the substrate from the input UV light. Areas covered by the photomasks remain intact with the base layer while the areas exposed to the UV light are washed away, thus creating a micropattern. This technology was limited to a two-dimensional, disc-shaped design as the boundaries between the exposed and roofed regions are always in a parallel arrangement with the direction of the light.
Professor Kim’s research team discovered that: 1) the areas exposed to UV light lowered the concentration of oxygen and thus resulted in oxygen diffusion; and 2) manipulation of the diffusion speed and direction allowed control of the growth, shape and size of the polymers. Based on these findings, the team developed a new photolithographic technology that enabled the production of micropatterns with three-dimensional structures in various shapes and sizes.
Oxygen was considered an inhibitor during photopolymerization. Photoresist under UV light creates radicals which initialize a chemical reaction. These radicals are eliminated with the presence of oxygen and thus prevents the reaction. This suggests that the photoresist must be exposed to UV light for an extended time to completely remove oxygen for a chemical reaction to begin.
The research team, however, exploited the presence of oxygen. While the region affected by the UV light lowered oxygen concentration, the concentration in the untouched region remained unchanged. This difference in the concentrations caused a diffusion of oxygen to the region under UV light.
When the speed of the oxygen flow is slow, the diffusion occurs in parallel with the direction of the UV light. When fast, the diffusion process develops horizontally, outward from the area affected by the UV light. Professor Kim and his team proved this phenomenon both empirically and theoretically. Furthermore, by injecting an external oxygen source, the team was able to manipulate diffusion strength and direction, and thus control the shape and size of the polymer. The use of the polymerization inhibitors enabled and facilitated the fabrication of complex, three-dimensional micropatterns.
Professor Kim said, “While 3D printing is considered an innovative manufacturing technology, it cannot be used for mass-production of microscopic products. The new photolithographic technology will have a broad impact on both the academia and industry especially because existing, conventional photolithographic equipment can be used for the development of more complex micropatterns.” His newest technology will enhance the manufacturing process of three-dimensional polymers which were considered difficult to be commercialized.
The research was also dedicated to the late Professor Seung-Man Yang of the Department of Chemical and Biomolecular Engineering at KAIST. He was considered one of the greatest scholars in Korea in the field of hydrodynamics and colloids.
Picture 1: Featured Image of Nature Communications, March 2015
Picture 2: Polymers with various shapes and sizes produced with the new photolithographic technology developed by Professor Kim
2015.04.06 View 9681 -
A Key Signal Transduction Pathway Switch in Cardiomyocyte Identified
A KAIST research team has identified the fundamental principle in deciding the fate of cardiomyocyte or heart muscle cells. They have determined that it depends on the degree of stimulus in β-adrenergic receptor signal transduction pathway in the cardiomyocyte to control cells' survival or death. The findings, the team hopes, can be used to treat various heart diseases including heart failure.
The research was led by KAIST Department of Bio and Brain Engineering Chair Professor Kwang-Hyun Cho and conducted by Dr. Sung-Young Shin (lead author) and Ph.D. candidates Ho-Sung Lee and Joon-Hyuk Kang. The research was conducted jointly with GIST (Gwangju Institute of Science and Technology) Department of Biological Sciences Professor Do-Han Kim’s team. The research was supported by the Ministry of Science, ICT and Future Planning, Republic of Korea, and the National Research Foundation of Korea. The paper was published in Nature Communications on December 17, 2014 with the title, “The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes.”
The β-adrenergic receptor signal transduction pathway can promote cell survival (mediated by β2 receptors), but also can result in cell death by inducing toxin (mediated by β1 receptors) that leads to various heart diseases including heart failure. Past attempts to identify the fundamental principle in the fate determining process of cardiomyocyte based on β-adrenergic receptor signalling concluded without much success.
The β-adrenergic receptor is a type of protein on the cell membrane of cardiomyocyte (heart muscle cell) that when stimulated by neurohormones such as epinephrine or norepinephrine would transduce signals making the cardiomyocyte contract faster and stronger.
The research team used large-scale computer simulation analysis and systems biology to identify ERK* and ICER** signal transduction pathways mediated by a feed-forward circuit as a key molecular switch that decides between cell survival and death.
Weak β-adrenergic receptor stimulations activate ERK signal transduction pathway, increasing Bcl-2*** protein expression to promote cardiomyocyte survival. On the other hand, strong β-adrenergic receptor stimulations activate ICER signal transduction pathway, reducing Bcl-2 protein expression to promote cardiomyocyte death.
Researchers used a systems biology approach to identify the mechanism of B-blocker****, a common drug prescribed for heart failure. When cardiomyocyte is treated with β1 inhibitor, strong stimulation on β-adrenergic receptor increases Bcl-2 expression, improving the chance of cardiomyocyte survival, a cell protection effect.
Professor Kwang-Hyun Cho said, “This research used systems biology, an integrated, convergence research of IT (information technology) and BT (biotechnology), to successfully identify the mechanism in deciding the fate of cardiomyocytes based on the β-adrenergic receptor signal transduction pathway for the first time. I am hopeful that this research will enable the control of cardiomyocyte survival and death to treat various heart diseases including heart failure.”
Professor Cho’s team was the first to pioneer a new field of systems biology, especially concerning the complex signal transduction network involved in diseases. Their research is focused on modelling, analyzing simulations, and experimentally proving signal pathways. Professor Cho has published 140 articles in international journals including Cell, Science, and Nature.
* ERK (Extracellular signal-regulated kinases): Signal transduction molecule involved in cell survival
** ICER (Inducible cAMP early repressor): Signal transduction molecule involved in cell death
*** Bcl-2 (B-cell lymphoma 2): Key signal transduction molecule involved in promotion of cell survival
**** β-blocker: Drug that acts as β-adrenergic receptor inhibitor known to slow the progression of heart failure, hence used most commonly in medicine.
Picture: A schematic diagram for the β-AR signalling network
2015.01.05 View 12238