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X-ray Scattering Shines Light on Protein Folding
- Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. - KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30. When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s. “Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.” Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies. The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process. The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state. “We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.” Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures. Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS). Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state. Publications: Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117 Profile: Hyotcherl Ihee, Ph.D. Professor firstname.lastname@example.org http://time.kaist.ac.kr/ Ihee Laboratory Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea Profile: Young Min Rhee, Ph.D. Professor email@example.com http://singlet.kaist.ac.kr Rhee Research Group Department of Chemistry KAIST https://www.kaist.ac.kr Daejeon 34141, Korea (END)
A Theoretical Boost to Nano-Scale Devices
- Researchers calculate the quasi-Fermi levels in molecular junctions applying an initio approach. - Semiconductor companies are struggling to develop devices that are mere nanometers in size, and much of the challenge lies in being able to more accurately describe the underlying physics at that nano-scale. But a new computational approach that has been in the works for a decade could break down these barriers. Devices using semiconductors, from computers to solar cells, have enjoyed tremendous efficiency improvements in the last few decades. Famously, one of the co-founders of Intel, Gordon Moore, observed that the number of transistors in an integrated circuit doubles about every two years—and this ‘Moore’s law’ held true for some time. In recent years, however, such gains have slowed as firms that attempt to engineer nano-scale transistors hit the limits of miniaturization at the atomic level. Researchers with the School of Electrical Engineering at KAIST have developed a new approach to the underlying physics of semiconductors. “With open quantum systems as the main research target of our lab, we were revisiting concepts that had been taken for granted and even appear in standard semiconductor physics textbooks such as the voltage drop in operating semiconductor devices,” said the lead researcher Professor Yong-Hoon Kim. “Questioning how all these concepts could be understood and possibly revised at the nano-scale, it was clear that there was something incomplete about our current understanding.” “And as the semiconductor chips are being scaled down to the atomic level, coming up with a better theory to describe semiconductor devices has become an urgent task.” The current understanding states that semiconductors are materials that act like half-way houses between conductors, like copper or steel, and insulators, like rubber or Styrofoam. They sometimes conduct electricity, but not always. This makes them a great material for intentionally controlling the flow of current, which in turn is useful for constructing the simple on/off switches—transistors—that are the foundation of memory and logic devices in computers. In order to ‘switch on’ a semiconductor, a current or light source is applied, exciting an electron in an atom to jump from what is called a ‘valence band,’ which is filled with electrons, up to the ‘conduction band,’ which is originally unfilled or only partially filled with electrons. Electrons that have jumped up to the conduction band thanks to external stimuli and the remaining ‘holes’ are now able to move about and act as charge carriers to flow electric current. The physical concept that describes the populations of the electrons in the conduction band and the holes in the valence band and the energy required to make this jump is formulated in terms of the so-called ‘Fermi level.’ For example, you need to know the Fermi levels of the electrons and holes in order to know what amount of energy you are going to get out of a solar cell, including losses. But the Fermi level concept is only straightforwardly defined so long as a semiconductor device is at equilibrium—sitting on a shelf doing nothing—and the whole point of semiconductor devices is not to leave them on the shelf. Some 70 years ago, William Shockley, the Nobel Prize-winning co-inventor of the transistor at the Bell Labs, came up with a bit of a theoretical fudge, the ‘quasi-Fermi level,’ or QFL, enabling rough prediction and measurement of the interaction between valence band holes and conduction band electrons, and this has worked pretty well until now. “But when you are working at the scale of just a few nanometers, the methods to theoretically calculate or experimentally measure the splitting of QFLs were just not available,” said Professor Kim. This means that at this scale, issues such as errors relating to voltage drop take on much greater significance. Kim’s team worked for nearly ten years on developing a novel theoretical description of nano-scale quantum electron transport that can replace the standard method—and the software that allows them to put it to use. This involved the further development of a bit of math known as the Density Functional Theory that simplifies the equations describing the interactions of electrons, and which has been very useful in other fields such as high-throughput computational materials discovery. For the first time, they were able to calculate the QFL splitting, offering a new understanding of the relationship between voltage drop and quantum electron transport in atomic scale devices. In addition to looking into various interesting non-equilibrium quantum phenomena with their novel methodology, the team is now further developing their software into a computer-aided design tool to be used by semiconductor companies for developing and fabricating advanced semiconductor devices. The study, featured at the Proceedings of the National Academy of Sciences of the USA on May 12, was supported by the National Research Foundation and the Korea Institute of Science and Technology Information Supercomputing Center. Image caption: The newly developed formalism and QFL splitting analysis led to new ways of characterizing extremely scaled-down semiconductor devices and the technology computer-aided design (TCAD) of next- generation nano-electronic/energy/bio devices. Image credit: Yong-Hoon Kim, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Juho Lee, Hyeonwoo Yeo, and Yong-Hoon Kim. (2020) ‘Quasi-Fermi level splitting in nanoscale junctions from ab initio.’ Proceedings of the National Academy of Sciences of the United States of America (PNAS), Volume 117, Issue 19, pp.10142-101488. Available online at https://doi.org/10.1073/pnas.1921273117 Profile: Yong-Hoon Kim Professor firstname.lastname@example.org http://nanocore.kaist.ac.kr/ 1st-Principles Nano-Device Computing Lab School of Electrical Engineering KAIST (END)
3D Hierarchically Porous Nanostructured Catalyst Helps Efficiently Reduce CO2
- This new catalyst will bring CO2 one step closer to serving as a sustainable energy source. - KAIST researchers developed a three-dimensional (3D) hierarchically porous nanostructured catalyst with carbon dioxide (CO2) to carbon monoxide (CO) conversion rate up to 3.96 times higher than that of conventional nanoporous gold catalysts. This new catalyst helps overcome the existing limitations of the mass transport that has been a major cause of decreases in the CO2 conversion rate, holding a strong promise for the large-scale and cost-effective electrochemical conversion of CO2 into useful chemicals. As CO2 emissions increase and fossil fuels deplete globally, reducing and converting CO2 to clean energy electrochemically has attracted a great deal of attention as a promising technology. Especially due to the fact that the CO2 reduction reaction occurs competitively with hydrogen evolution reactions (HER) at similar redox potentials, the development of an efficient electrocatalyst for selective and robust CO2 reduction reactions has remained a key technological issue. Gold (Au) is one of the most commonly used catalysts in CO2 reduction reactions, but the high cost and scarcity of Au pose obstacles for mass commercial applications. The development of nanostructures has been extensively studied as a potential approach to improving the selectivity for target products and maximizing the number of active stable sites, thus enhancing the energy efficiency. However, the nanopores of the previously reported complex nanostructures were easily blocked by gaseous CO bubbles during aqueous reactions. The CO bubbles hindered mass transport of the reactants through the electrolyte, resulting in low CO2 conversion rates. In the study published in the Proceedings of the National Academy of Sciences of the USA (PNAS) on March 4, a research group at KAIST led by Professor Seokwoo Jeon and Professor Jihun Oh from the Department of Materials Science and Engineering designed a 3D hierarchically porous Au nanostructure with two different sizes of macropores and nanopores. The team used proximity-field nanopatterning (PnP) and electroplating techniques that are effective for fabricating the 3D well-ordered nanostructures. The proposed nanostructure, comprised of interconnected macroporous channels 200 to 300 nanometers (nm) wide and 10 nm nanopores, induces efficient mass transport through the interconnected macroporous channels as well as high selectivity by producing highly active stable sites from numerous nanopores. As a result, its electrodes show a high CO selectivity of 85.8% at a low overpotential of 0.264 V and efficient mass activity that is up to 3.96 times higher than that of de-alloyed nanoporous Au electrodes. “These results are expected to solve the problem of mass transfer in the field of similar electrochemical reactions and can be applied to a wide range of green energy applications for the efficient utilization of electrocatalysts,” said the researchers. This work was supported by the National Research Foundation (NRF) of Korea. Image credit: Professor Seokwoo Jeon and Professor Jihun Oh, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Hyun et al. (2020) Hierarchically porous Au nanostructures with interconnected channels for efficient mass transport in electrocatalytic CO2 reduction. Proceedings of the National Academy of Sciences of the USA (PNAS). Available online at https://doi.org/10.1073/pnas.1918837117 Profile: Seokwoo Jeon, PhD Professor email@example.com http://fdml.kaist.ac.kr Department of Materials Science and Engineering (MSE) https://www.kaist.ac.kr Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea Profile: Jihun Oh, PhD Associate Professor firstname.lastname@example.org http://les.kaist.ac.kr Department of Materials Science and Engineering (MSE) Department of Energy, Environment, Water and Sustainability (EEWS) KAIST Profile: Gayea Hyun PhD Candidate email@example.com http://fdml.kaist.ac.kr Flexible Devices and Metamaterials Laboratory (FDML) Department of Materials Science and Engineering (MSE) KAIST Profile: Jun Tae Song, PhD Assistant Professor firstname.lastname@example.org http://www.cstf.kyushu-u.ac.jp/~ishihara-lab/ Department of Applied Chemistry https://www.kyushu-u.ac.jp Kyushu UniversityFukuoka, Japan (END)
Coordination Chemistry and Alzheimer’s Disease
It has become evident recently that the interactions between copper and amyloid-b neurotoxically impact the brain of patients with Alzheimer’s disease. KAIST researchers have reported a new strategy to alter the neurotoxicity in Alzheimer’s disease by using a rationally designed chemical reagent. This strategy, developed by Professor Mi Hee Lim from the Department of Chemistry, can modify the coordination sphere of copper bound to amyloid-b, effectively inhibiting copper’s binding to amyloid-b and altering its aggregation and toxicity. Their study was featured in PNAS last month. The researchers developed a small molecule that is able to directly interact with the coordination sphere of copper–amyloid-b complexes followed by modifications via either covalent conjugation, oxidation, or both under aerobic conditions. The research team simply utilized copper–dioxygen chemistry to design a chemical reagent. Answering how peptide modifications by a small molecule occur remains very challenging. The system includes transition metals and amyloidogenic proteins and is quite heterogeneous, since they are continuously being changed. It is critical to carefully check the multiple variables such as the presence of dioxygen and the type of transition metal ions and amyloidogenic proteins in order to identify the underlying mechanisms and target specificity of the chemical reagent. The research team employed various biophysical and biochemical methods to determine the mechanisms for modifications on the coordination sphere of copper–Aꞵ complexes. Among them, peptide modifications were mainly analyzed using electrospray ionization-mass spectrometry. Mass spectrometry (MS) has been applied to verify such peptide modifications by calculating the shift in exact mass. The research team also performed collision-induced dissociation (CID) of the target ion detected by MS to pinpoint which amino acid residue is specifically modified. The CID fragmentizes the amide bond located between the amino acid residues. This fragmental analysis allows us to identify the specific sites of peptide modifications. The copper and amyloid-b complexes represent a pathological connection between metal ions and amyloid-b in Alzheimer’s disease. Recent findings indicate that copper and amyloid-b can directly contribute toward neurodegeneration by producing toxic amyloid-b oligomers and reactive oxygen species. Professor Lim said, “This study illustrates the first experimental evidence that the 14th histidine residue in copper–amyloid-b complexes can be specifically modified through either covalent conjugation, oxidation, or both. Considering the neurotoxic implications of the interactions between copper and amyloid-b, such modifications at the coordination sphere of copper in amyloid-b could effectively alter its properties and toxicity.” “This multidisciplinary study with an emphasis on approaches, reactivities, and mechanisms looks forward to opening a new way to develop candidates of anti-neurodegenerative diseases,” she added. The National Research Foundation of Korea funded this research.
Recombinant E. Coli As a Biofactory for the Biosynthesis of Diverse Nanomaterials
(Distinguished Professor Lee and PhD candidate Choi) A metabolic research group at KAIST and Chung-Ang University in Korea has developed a recombinant E. coli strain that biosynthesizes 60 different nanomaterials covering 35 elements on the periodic table. Among the elements, the team could biosynthesize 33 novel nanomaterials for the first time, advancing the forward design of nanomaterials through the biosynthesis of various single and multi-elements. The study analyzed the nanomaterial biosynthesis conditions using a Pourbaix diagram to predict the producibility and crystallinity. Researchers studied a Pourbaix diagram to predict the stable chemical species of each element for nanomaterial biosynthesis at varying levels of reduction potential (Eh) and pH. Based on the Pourbaix diagram analyses, the initial pH of the reaction was changed from 6.5 to 7.5, resulting in the biosynthesis of various crystalline nanomaterials that were previously amorphous or not synthesized. This strategy was extended to biosynthesize multi-element nanomaterials. Various single and multi-element nanomaterials biosynthesized in this research can potentially serve as new and novel nanomaterials for industrial applications such as catalysts, chemical sensors, biosensors, bioimaging, drug delivery, and cancer therapy. A research group consisting of PhD candidate Yoojin Choi, Associate Professor Doh Chang Lee, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST and Associate Professor Tae Jung Park of the Department of Chemistry at Chung-Ang University reported the synthesis. This study, entitled “Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials,” was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on May 21. A recent successful biosynthesis of nanomaterials under mild conditions without requiring physical and chemical treatments has triggered the exploration of the full biosynthesis capacity of a biological system for producing a diverse range of nanomaterials as well as for understanding biosynthesis mechanisms for crystalline versus amorphous nanomaterials. There has been increased interest in synthesizing various nanomaterials that have not yet been synthesized for various applications including semiconducting materials, enhanced solar cells, biomedical materials, and many others. This research reports the construction of a recombinant E. coli strain that co-expresses metallothionein, a metal binding protein, and phytochelatin synthase that synthesizes the metal-binding peptide phytochelatin for the biosynthesis of various nanomaterials. Subsequently, an E. coli strain was engineered to produce a diverse range of nanomaterials, including those never biosynthesized before, by using 35 individual elements from the periodic table and also by combining multi-elements. Distinguished Professor Lee said, “An environmentally-friendly and sustainable process is of much interest for producing nanomaterials by not only chemical and physical methods but biological synthesis. Moreover, there has been much attention paid to producing diverse and novel nanomaterials for new industrial applications. This is the first report to predict the biosynthesis of various nanomaterials, by far the largest number of various single- and multi-elements nanomaterials. The strategies used for nanomaterial biosynthesis in this research will be useful for further diversifying the portfolio of nanomaterials that can be manufactured.” Figure: The biosynthesis of diverse nanomaterials using recombinant E. coli. This schematic diagram shows the overall conceptualization of the biosynthesis of various single and multi-element nanomaterials using recombinant E. coli under incubation with corresponding elemental precursors. The 35 elements that were tested to biosynthesize nanomaterials are shown in black circles on the periodic table.
Professor Seyun Kim Identifies a Neuron Signal Controlling Molecule
A research team led by Professor Seyun Kim of the Department of Biological Sciences at KAIST has identified inositol pyrophosphates as the molecule that strongly controls neuron signaling via synaptotagmin. Professors Tae-Young Yoon of Yonsei University’s Y-IBS and Sung-Hyun Kim of Kyung Hee University’s Department of Biomedical Science also joined the team. The results were published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30, 2016. This interdisciplinary research project was conducted by six research teams from four different countries and covered a wide scope of academic fields, from neurobiology to super resolution optic imaging. Inositol pyrophosphates such as 5-diphosphoinositol pentakisphos-phate (5-IP7), which naturally occur in corns and beans, are essential metabolites in the body. In particular, inositol hexakisphosphate (IP6) has anti-cancer properties and is thought to have an important role in cell signaling. Inositol pentakisphosphate (IP7) differs from IP6 by having an additional phosphate group, which was first discovered 20 years ago. IP7 has recently been identified as playing a key role in diabetes and obesity. Psychopathy and neurodegenerative diseases are known to result from the disrupted balance of inositol pyrophosphates. However, the role and the mechanism of action of IP7 in brain neurons and nerve transmission remained unknown. Professor Kim’s team has worked on inositol pyrophosphates for several years and discovered that very small quantities of IP7 control cell-signaling transduction. Professor Yoon of Yonsei University identified IP7 as a much stronger inhibitor of neuron signaling compared to IP6. In particular, IP7 directly suppresses synaptotagmin, one of the key proteins in neuron signaling. Moreover, Professor Kim of Kyung Hee University observed IP7 inhibition in sea horse neurons. Together, the joint research team identified inositol pyrophosphates as the key switch metabolite of brain-signaling transduction. The researchers hope that future research on synaptotagmin and IP7 will reveal the mechanism of neuron-signal transduction and thus enable the treatment of neurological disorders. These research findings were the result of cooperation of various science and technology institutes: KAIST, Yonsei-IBS (Institute for Basic Science), Kyung Hee University, Sungkyunkwan University, KIST, University of Zurich in Switzerland, and Albert-Ludwigs-University Freiburg in Germany. Schematic Image of Controlling the Synaptic Exocytotic Pathway by 5-IP7 , Helping the Understanding of the Signaling Mechanisms of Inositol Pyrophosphates
Artificial Antibody-based Therapeutic Candidate for Lung Cancer Developed
Professor Hak-Sung Kim of Biological Sciences at KAIST publishes a cover article on artificial antibody in "Molecular Therapy". Repebody-based lung cancer therapeutic drug candidate developed Repebody-based protein demonstrates the possibility of the development of a new drug KAIST Biological Sciences Department’s Professor Hak-Sung Kim, in collaboration with Professor Eun-Kyung Cho from the College of Medicine at Chungnam National University, has successfully developed an artificial antibody-based, or repebody, cancer therapeutic candidate. These research results were published as a cover paper of the July edition of Molecular Therapy. The repebody developed by Professor Kim and his team strongly binds to interleukin-6, a cancer-causing factor. It has also been confirmed that the repebody can significantly inhibit the proliferation of cancer cells in non-small-cell lung cancer animal model. Numerous multinational pharmaceutical and biotechnology companies have invested astronomical amounts of money in research for the development of protein therapeutics with low side effects and high efficacy. More than 20 kinds of such therapeutics are currently under clinical trials, and over 100 drugs are under clinical demonstration. Among these, the majority is antibody-based therapeutics, and most of the investments are heavily concentrated in this field. However, antibody production cost is very high because it has large molecular weights and complex structural properties, and this makes it difficult to engineer. Consequently, the development costs a great deal of time and money. In order to overcome the existing limitations of antibody-based therapeutics, Professor Kim and his team have developed a new artificial antibody, or repebody, which was published in Proceedings of the National Academy of Sciences (PNAS) in 2012. Based on this research, they have succeeded in developing a therapeutic candidate for treating non-small-cell lung cancer with a specifically strong cohesion to the cancer-causing factor, interleukin-6. Interleukin-6 is a crucial substance within the body that is involved in immune and inflammatory-related signals. When abnormally expressed, it activates various carcinogenic pathways and promotes tumor growth and metastasis. Because of its importance, multinational pharmaceutical companies are heavily investing in developing therapeutics that can inhibit the signaling of interleukin-6. In this study, Professor Kim and his team observed that a repebody consists of repeated modules, and they conceived a module-based affinity amplification technology that can effectively increase the binding affinity with the disease target. The developed therapeutic candidate has been confirmed in cell and animal experiments to show low immunogenicity, as well as to strongly inhibit the proliferation of non-small-cell lung cancer. Furthermore, by investigating the complex structure of the repebody with interleukin-6, Professor Kim has identified its mechanism, which demonstrated the potential for therapeutic development. The researchers are currently carrying out pre-clinical trials for acquiring permission to perform clinical trials on animals with non-small-cell lung cancer. The repebody can be developed into a new protein drug after demonstrating its safety and efficacy. Professor Hak-Sung Kim and his team have confirmed that the repebody can be utilized as a new protein drug, and this will be a significant contribution to Korea’s protein drugs and biotechnology industry development. The research was supported by the Future Pioneer Industry project and sponsored by the Ministry of Science, ICT and Future Planning. Figure 1. Professor Kim’s article published as the cover article of July edition of Molecular Therapy Figure 2. Clinical proof of the repebody’s inhibition of cancer growth using animal models
Materials Developed for Sodium Rechargeable Battery by EEWS
The research group of Professor William Goddard III, You-Sung Jung, and Jang-Wook Choi from the Graduate School of Energy, Environment, Water, and Sustainability (EEWS) at KAIST has developed a new sodium-ion rechargeable battery which operates at a high voltage, can be charged, and stably discharges over 10,000 cycles. The research results were published in the online version of the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on December 30, 2013. Since the material costs of sodium rechargeable batteries is 30 to 40 times lower than lithium batteries, it has received attention as an energy saving tool for smart grids and as the next generation of lithium rechargeable batteries. Until now, sodium-ion rechargeable batteries have had issues with stability when charging and discharging. The research group developed a vanadium-based electrode to solve these problems. The group said follow-up research will be continued to develop advanced technology on sodium rechargeable batteries as it is still currently in the beginning stages. The research team: From left to right is Professors William Goddard, You-Sung Jung, and Jang-Wook Choi
Secondary, High Capacity Battery developed from Rice Husks
Rice husks, a waste product from rice polishing, has been successfully utilized as the silicon anode for use in high capacity lithium ion secondary batteries. The new silicon anode derived from rice husks exhibit superior output and lifespan. Professor Choi Jang Wook (The Graduate School of Energy, Environment, Water and Sustainability (EEWS)) and Professor Park Seung Min (Department of Biochemistry) and their respective research teams separated naturally occurring, highly porous silica material within the rice husks and developed a 3-dimensional, highly porous silicon anode material. The result of the research effort was published in the online edition of the Proceedings of the National Academy of Sciences (PNAS) journal, a world renowned journal in the field of natural sciences. Silicon has attracted much attention as anode material for next generation lithium ion secondary batteries because it exhibits 3~5 times higher capacity than conventional graphene. The high capacity will pave the way to lithium secondary batteries with higher energy densities than conventional batteries. It is anticipated that the application of silicon batteries will yield electronic devices with a longer duration for use in addition to electronic vehicles boasting longer mileage. The silicon anode is based on the 3-dimensional, highly porous structure of rice husks which remedies the problematic extreme volume expansion of conventional silicon anodes. Utilization of inexpensive rice husks to create high value silicon anodes will cause a ripple effect on the industry and academia.
Creation of Synthetic Antibodies: Professor Hak Seong Kim
Synthetics antibodies which can replace antibodies from humans used as ingredients of medicines have been developed. It can increase the costs to 1/100 of the current costs and is much easier to develop. It is expected that the development period will be shortened from 10 years to 5. Prof. Hak Seong Kim from the Biology department of KAIST conducted a joint research with Prof. Dong Seob Kim to reconstruct proteins and has succeeded. The synthetic antibody displays much strength in terms of its productivity, structural formation, and bonding capability, and is thus regarded as an ideal protein. It can replace the antigens that are currently in use. It is expected that Korea will therefore be able to lead the world market for protein medicines which is a 192trillion won industry. The original antibody has been used for not only treating diseases, but also for various other applications in the fields of medical sciences and biology. However, it is produced through a very complex process involving the incubation of animal cells, and is therefore very expensive. Also, most antibodies are already patented by more developed countries, so a high royalty fee must be paid. Because of this, many countries including Korea has been concentrating on developing biosimilars copying the antibody medicines for which the patents have already expired. This causes Korea to be behind in the development of antibody protein pharmaceuticals. Prof. Kim’s research team has focused on the face that the protein existing in some eels are not antibodies but functions as one, and has been successful in developing a synthetic antibody. The synthetic antibody can be mass produced from the colon bacillus, which allows it to be produced at 1/100 the original cost. It is in a module structure which allows the structuring of the antibody into the desired structure, enabling it to be developed into a protein-based medicine within 5 years. Together with this, the coherence with the important antigens can be easily controlled, thus allowing for highly effective treatments, less side-effects, high security regarding heat and pH, and the immunogen levels being negligeable. This suggests a very high rate of the antibody being converted into a protein based medication. The synthetic antibody technology has been tested as a sample for the cure for lung diseases and rheumatism and has been proven to be appropriate. Animal testing will be conducted soon. Prof Kim said “The original antibodies had a small area allowing the bonding with antibodies, creating barriers for raising bonding strength and structuring. The newly created antibody carries only the strengths and will become a new protein based medicine purely created by Korean technology to replace the antibodies currently used in medications.” Furthermore, he added that, “The synthesized antibody structuring and designing technology will be widely used in the areas of detecting, diagnosing, and analyzing diseases.” At the same time, this research result has been published in the Feb 10th issue of the PNAS, and has been supported by the future promising pioneer business program held by the Ministry of Education and Technology.
Bioengineers develop a new strategy for accurate prediction of cellular metabolic fluxes
A team of pioneering South Korean scientists has developed a new strategy for accurately predicting cellular metabolic fluxes under various genotypic and environmental conditions. This groundbreaking research is published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS) on August 2, 2010. To understand cellular metabolism and predict its metabolic capability at systems-level, systems biological analysis by modeling and simulation of metabolic network plays an important role. The team from the Korea Advanced Institute of Science and Technology (KAIST), led by Distinguished Professor Sang Yup Lee, focused their research on the development of a new strategy for more accurate prediction of cellular metabolism. “For strain improvement, biologists have made every effort to understand the global picture of biological systems and investigate the changes of all metabolic fluxes of the system under changing genotypic and environmental conditions,” said Lee. The accumulation of omics data, including genome, transcriptome, proteome, metabolome, and fluxome, provides an opportunity to understand the cellular physiology and metabolic characteristics at systems-level. With the availability of the fully annotated genome sequence, the genome-scale in silico (means “performed on computer or via computer simulation.”) metabolic models for a number of organisms have been successfully developed to improve our understanding on these biological systems. With these advances, the development of new simulation methods to analyze and integrate systematically large amounts of biological data and predict cellular metabolic capability for systems biological analysis is important. Information used to reconstruct the genome-scale in silico cell is not yet complete, which can make the simulation results different from the physiological performances of the real cell. Thus, additional information and procedures, such as providing additional constraints (constraint: a term to exclude incorrect metabolic fluxes by restricting the solution space of in silico cell) to the model, are often incorporated to improve the accuracy of the in silico cell. By employing information generated from the genome sequence and annotation, the KAIST team developed a new set of constraints, called Grouping Reaction (GR) constraints, to accurately predict metabolic fluxes. Based on the genomic information, functionally related reactions were organized into different groups. These groups were considered for the generation of GR constraints, as condition- and objective function- independent constraints. Since the method developed in this study does not require complex information but only the genome sequence and annotation, this strategy can be applied to any organism with a completely annotated genome sequence. “As we become increasingly concerned with environmental problems and the limits of fossil resources, bio-based production of chemicals from renewable biomass has been receiving great attention. Systems biological analysis by modeling and simulation of biological systems, to understand cellular metabolism and identify the targets for the strain improvement, has provided a new paradigm for developing successful bioprocesses,” concluded Lee. This new strategy for predicting cellular metabolism is expected to contribute to more accurate determination of cellular metabolic characteristics, and consequently to the development of metabolic engineering strategies for the efficient production of important industrial products and identification of new drug targets in pathogens.”
Native-like Spider Silk Produced in Metabolically Engineered Bacterium
Microscopic picture of 285 kilodalton recombinant spider silk fiber Researchers have long envied spiders’ ability to manufacture silk that is light-weighted while as strong and tough as steel or Kevlar. Indeed, finer than human hair, five times stronger by weight than steel, and three times tougher than the top quality man-made fiber Kevlar, spider dragline silk is an ideal material for numerous applications. Suggested industrial applications have ranged from parachute cords and protective clothing to composite materials in aircrafts. Also, many biomedical applications are envisioned due to its biocompatibility and biodegradability. Unfortunately, natural dragline silk cannot be conveniently obtained by farming spiders because they are highly territorial and aggressive. To develop a more sustainable process, can scientists mass-produce artificial silk while maintaining the amazing properties of native silk? That is something Sang Yup Lee at the Korea Advanced Institute of Science and Technology (KAIST) in Daejeon, the Republic of Korea, and his collaborators, Professor Young Hwan Park at Seoul National University and Professor David Kaplan at Tufts University, wanted to figure out. Their method is very similar to what spiders essentially do: first, expression of recombinant silk proteins; second, making the soluble silk proteins into water-insoluble fibers through spinning. For the successful expression of high molecular weight spider silk protein, Professor Lee and his colleagues pieced together the silk gene from chemically synthesized oligonucleotides, and then inserted it into the expression host (in this case, an industrially safe bacterium Escherichia coli which is normally found in our gut). Initially, the bacterium refused to the challenging task of producing high molecular weight spider silk protein due to the unique characteristics of the protein, such as extremely large size, repetitive nature of the protein structure, and biased abundance of a particular amino acid glycine. “To make E. coli synthesize this ultra high molecular weight (as big as 285 kilodalton) spider silk protein having highly repetitive amino acid sequence, we helped E. coli overcome the difficulties by systems metabolic engineering,” says Sang Yup Lee, Distinguished Professor of KAIST, who led this project. His team boosted the pool of glycyl-tRNA, the major building block of spider silk protein synthesis. “We could obtain appreciable expression of the 285 kilodalton spider silk protein, which is the largest recombinant silk protein ever produced in E. coli. That was really incredible.” says Dr. Xia. But this was only step one. The KAIST team performed high-cell-density cultures for mass production of the recombinant spider silk protein. Then, the team developed a simple, easy to scale-up purification process for the recombinant spider silk protein. The purified spider silk protein could be spun into beautiful silk fiber. To study the mechanical properties of the artificial spider silk, the researchers determined tenacity, elongation, and Young’s modulus, the three critical mechanical parameters that represent a fiber’s strength, extensibility, and stiffness. Importantly, the artificial fiber displayed the tenacity, elongation, and Young’s modulus of 508 MPa, 15%, and 21 GPa, respectively, which are comparable to those of the native spider silk. “We have offered an overall platform for mass production of native-like spider dragline silk. This platform would enable us to have broader industrial and biomedical applications for spider silk. Moreover, many other silk-like biomaterials such as elastin, collagen, byssus, resilin, and other repetitive proteins have similar features to spider silk protein. Thus, our platform should also be useful for their efficient bio-based production and applications,” concludes Professor Lee. This work is published on July 26 in the Proceedings of the National Academy of Sciences (PNAS) online.
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