research
-
Skin Hardness to Estimate Better Human Thermal Status
(Professor Young-Ho Cho and Researcher Sunghyun Yoon)
Under the same temperature and humidity, human thermal status may vary due to individual body constitution and climatic environment. A KAIST research team previously developed a wearable sweat rate sensor for human thermal comfort monitoring. Furthering the development, this time they proposed skin hardness as an additional, independent physiological sign to estimate human thermal status more accurately. This novel approach can be applied to developing systems incorporating human-machine interaction, which requires accurate information about human thermal status.
Professor Young-Ho Cho and his team from the Department of Bio and Brain Engineering had previously studied skin temperature and sweat rate to determine human thermal comfort, and developed a watch-type sweat rate sensor that accurately and steadily detects thermal comfort last February (title: Wearable Sweat Rate Sensors for Human Thermal Comfort Monitoring ).
However, skin temperature and sweat rate are still not enough to estimate exact human thermal comfort. Hence, an additional indicator is required for enhancing the accuracy and reliability of the estimation and the team selected skin hardness. When people feel hot or cold, arrector pili muscles connected to hair follicles contract and expand, and skin hardness comes from this contraction and relaxation of the muscles. Based on the phenomenon of changing skin hardness, the team proposed skin hardness as a new indicator for measuring human thermal sensation.
With this new estimation model using three physiological signs for estimating human thermal status, the team conducted human experiments and verified that skin hardness is effective and independent from the two conventional physiological signs. Adding skin hardness to the conventional model can reduce errors by 23.5%, which makes its estimation more reliable.
The team will develop a sensor that detects skin hardness and applies it to cognitive air-conditioning and heating systems that better interact with humans than existing systems.
Professor Cho said, “Introducing this new indicator, skin hardness, elevates the reliability of measuring human thermal comfort regardless of individual body constitution and climatic environment. Based on this method, we can develop a personalized air conditioning and heating system that will allow affective interaction between humans and machines by sharing both physical and mental health conditions and emotions.”
This research, led by researchers Sunghyun Yoon and Jai Kyoung Sim, was published in Scientific Reports, Vol.8, Article No.12027 on August 13, 2018. (pp.1-6)
Figure 1. Measuring human thermal status through skin hardness
Figure 2. The instrument used for measuring human thermal status through skin hardness
2018.10.17 View 6511 -
High-Performance Flexible Transparent Force Touch Sensor for Wearable Devices
Researchers reported a high-performance and transparent nanoforce touch sensor by developing a thin, flexible, and transparent hierarchical nanocomposite (HNC) film. The research team says their sensor simultaneously features all the necessary characters for industrial-grade application: high sensitivity, transparency, bending insensitivity, and manufacturability.
Force touch sensors that recognize the location and pressure of external stimuli have received considerable attention for various applications, such as wearable devices, flexible displays, and humanoid robots. For decades, huge amounts of research and development have been devoted to improving pressure sensitivity to realize industrial-grade sensing devices. However, it remains a challenge to apply force touch sensors in flexible applications because sensing performance is subject to change and degraded by induced mechanical stress and deformation when the device is bent.
To overcome these issues, the research team focused on the development of non-air gap sensors to break away from the conventional technology where force touch sensors need to have air-gaps between electrodes for high sensitivity and flexibility.
The proposed non air-gap force touch sensor is based on a transparent nanocomposite insulator containing metal nanoparticles which can maximize the capacitance change in dielectrics according to the pressure, and a nanograting substrate which can increase transparency as well as sensitivity by concentrating pressure. As a result, the team succeeded in fabricating a highly sensitive, transparent, flexible force touch sensor that is mechanically stable against repetitive pressure.
Furthermore, by placing the sensing electrodes on the same plane as the neutral plane, the force touch sensor can operate, even when bending to the radius of the ballpoint pen, without changes in performance levels.
The proposed force touch has also satisfied commercial considerations in mass production such as large-area uniformity, production reproducibility, and reliability according to temperature and long-term use.
Finally, the research team applied the developed sensor to a pulse-monitoring capable healthcare wearable device and detected a real-time human pulse. In addition, the research team confirmed with HiDeep, Inc. that a seven-inch large-area sensor can be integrated into a commercial smartphone.
The team of Professor Jun-Bo Yoon, PhD student Jae-Young Yoo, and Dr. Min-Ho Seo from the School of Electrical Engineering carried out this study that was featured as a back cover in Advanced Functional Materials Journal.
PhD student Jae-Young Yoo who led this research said, "We successfully developed an industrial-grade force touch sensor by using a simple structure and fabrication process. We expect it to be widely used in user touch interfaces and wearable devices."
This research was supported by the Basic Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT, and also supported by the Open Innovation Lab Cooperation Project funded by the National Nano Fab Center.
Figure 1. Schematic illustration of a transparent, flexible force touch sensor (upper image) and sensitivity enhancement by using stress concentration (lower image).
2018.10.15 View 6809 -
Trigger of the Hyperactivation of Fibrosis Identified
(Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering)
Scientists have been investigating the negative effects that the hyperactivation of fibrosis has on fibrotic diseases and cancer. A KAIST research team unveiled a positive feedback loop that bi-stably activates fibroblasts in collaboration with Samsung Medical Center. This finding will contribute to developing therapeutic targets for both fibrosis and cancer.
Human fibroblasts are dormant in normal tissue, but show radical activation during wound healing. However, the principle that induces their explosive activation has not yet been identified.
Here, Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering, in collaboration with Professor Seok-Hyung Kim from Samsung Medical Center, discovered the principle of a circuit that continuously activates fibroblasts.
They constructed a positive feedback loops (PFLs) where Twist1, Prrx1, and Tenascin-C (TNC) molecules consecutively activate fibroblasts. They confirmed that these are the main inducers of fibroblast activation by conducting various experiments, including molecular biological tests, mathematical modeling, animal testing, and computer simulations to conclude that they are the main inducers of fibroblast activation.
According to their research, Twist 1 is a key regulator of cancer-associated fibroblasts, which directly upregulates Prrx1 and then triggers TNC, which also increases Twist1 expression. This circuit consequently forms a Twist-Prrx1-TNC positive feedback loop.
Activated fibroblasts need to be deactivated after wounds are healed. However, if the PFLs continue, the fibroblasts become the major cause of worsening fibrotic diseases and cancers.
Therefore, the team expects that Twist1-Prrx1-TNC positive PFLs will be applied for novel and effective therapeutic targeting of fibrotic diseases and cancers.
This research was published in Nature Communications on August 1, 2018.
Figure 1. Twist1 increases tenascin-c expression in cancer-associated fibroblasts. Twist1 is a potent but indirect inducer of tenascin-c (TNC), which is essential for maintaining Twist1 expression in cancer-associated fibroblasts (CAFs).
Figure 2. Summary of the study. The Twist1-Prrx1-TNC positive feedback regulation provides clues for understanding the activation of fibroblasts during wound healing under normal conditions, as well as abnormally activated fibroblasts in pathological conditions such as cancerous and fibrotic diseases. Under normal conditions, the PFL acts as a reversible bistable switch by which the activation of fibroblasts is “ON" above a sufficient level of stimulation and “OFF" for the withdrawal of the stimulus. However, this switch can be permanently turned on under pathologic conditions by continued activation of the PFL, resulting in sustained proliferation of fibroblasts.
2018.10.11 View 6530 -
A Novel Biosensor to Advance Diverse High-Level Production of Microbial Cell Factories
A research group at KAIST presented a novel biosensor which can produce diverse, high-level microbial cell factories. The biosensor monitors the concentration of products and even intermediates when new strains are being developed. This strategy provides a new platform for manufacturing diverse natural products from renewable resources. The team succeeded in creating four natural products of high-level pharmaceutical importance with this strategy.
Malonyl-CoA is a major building block for many value-added chemicals including diverse natural products with pharmaceutical importance. However, due to the low availability of malonyl-CoA in bacteria, many malonyl-CoA-derived natural products have been produced by chemical synthesis or extraction from natural resources that are harmful to the environment and are unsustainable. For the sustainable biological production of malonyl-CoA-derived natural products, increasing the intracellular malonyl-CoA pool is necessary. To this end, the development of a robust and efficient malonyl-CoA biosensor was required to monitor the concentration of intracellular malonyl-CoA abundance as new strains are developed.
Metabolic engineering researchers at KAIST addressed this issue. This research reports the development of a simple and robust malonyl-CoA biosensor by repurposing a type III polyketide synthase (also known as RppA), which produces flaviolin, a colorimetric indicator of malonyl-CoA. Subsequently, the RppA biosensor was used for the rapid and efficient colorimetric screening of gene manipulation targets enabling enhanced malonyl-CoA abundance. The screened beneficial gene targets were employed for the high-level production of four representative natural products derived from malonyl-CoA. Compared with the previous strategies, which were expensive and time-consuming, the new biosensor could be easily applied to industrially relevant bacteria including Escherichia coli, Pseudomonas putida, and Corynebacterium glutamicum to enable a one-step process.
The study employs synthetic small regulatory RNA (sRNA) technology to rapidly and efficiently reduce endogenous target gene expression for improved malonyl-CoA production. The researchers constructed an E. coli genome-scale synthetic sRNA library targeting 1,858 genes covering all major metabolic genes in E. coli. This library was employed with the RppA biosensor to screen for gene targets which are believed to be beneficial for enhancing malonyl-CoA accumulation upon their expression knockdown.
From this colorimetric screening, 14 gene targets were selected, all of which were successful at significantly increasing the production of four natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin). Although specific examples are demonstrated in E. coli as a host, the researchers showed that the biosensor is also functional in P. putida and C. glutamicum, industrially important representative gram-negative and gram-positive bacteria, respectively. The malonyl-CoA biosensor developed in this research will serve as an efficient platform for the rapid development of strains capable of producing natural products crucial for the pharmaceutical, chemical, cosmetics, and food industries.
An important aspect of this work is that the high-performance strains constructed in this research were developed rapidly and easily by utilizing the simple approach of colorimetric screening, without involving extensive metabolic engineering approaches. 6-Methylsalicylic acid (an antibiotic) could be produced to the highest titer reported for E. coli, and the microbial production of aloesone (a precursor of aloesin, an anti-inflammatory agent/whitening agent) was achieved for the first time.
“A sustainable process for producing diverse natural products using renewable resources is of great interest. This study represents the development of a robust and efficient malonyl-CoA biosensor generally applicable to a wide range of industrially important bacteria. The capability of this biosensor for screening a large library was demonstrated to show that the rapid and efficient construction of high-performance strains is feasible. This research will be useful for further accelerating the development process of strains capable of producing valuable chemicals to industrially relevant levels,” said Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, who led the research.
This study entitled “Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria,” was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on October 02.
PhD students Dongsoo Yang and Won Jun Kim, MS student Shin Hee Ha, research staff Mun Hee Lee, Research Professor Seung Min Yoo, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Dr. Jong Hyun Choi of the Applied Microbiology Research Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) participated in this research.
Figure: Type III polyketide synthase (RppA) as a malonyl-CoA biosensor. RppA converts five molecules of malonyl-CoA into one molecule of red-colored flaviolin. This schematic diagram shows the overall conceptualization of the malonyl-CoA biosensor by indicating that higher malonyl-CoA abundance leads to higher production and secretion of flaviolin, resulting in a deeper red color of the culture. This system was employed for the enhanced production of four representative natural products (6-methylsalicylic acid, aloesone, resveratrol, and naringenin) from engineered E. coli strains.
2018.10.11 View 9879 -
Permanent, Wireless Self-charging System Using NIR Band
(Professor Jung-Yong Lee from the Graduate School of Energy, Environment, Water and Sustainability)
As wearable devices are emerging, there are numerous studies on wireless charging systems. Here, a KAIST research team has developed a permanent, wireless self-charging platform for low-power wearable electronics by converting near-infrared (NIR) band irradiation to electrical energy. This novel technology can be applied to flexible, wearable charging systems without needing any attachments.
Colloidal-quantum-dots (CQDs) are promising materials for manufacturing semiconductors; in particular, PbS-based CQDs have facile optical tunability from the visible to infrared wavelength region. Hence, they can be applied to various devices, such as lighting, photovoltaics (PVs), and photodetectors.
Continuous research on CQD-based optoelectronic devices has increased their power conversion efficiency (PCE) to 12%; however, applicable fields have not yet been found for them. Meanwhile, wearable electronic devices commonly face the problem of inconvenient charging systems because users have to constantly charge batteries attached to an energy source.
A joint team led by Professor Jung-Yong Lee from the Graduate School of Energy, Environment, Water and Sustainability and Jang Wok Choi from Seoul National University decided to apply CQD PVs, which have high quantum efficiency in NIR band to self-charging systems on wearable devices.
They employed a stable and efficient NIR energy conversion strategy. The system was comprised of a PbS CQD-based PV module, a flexible interdigitated lithium-ion battery, and various types of NIR-transparent films.
The team removed the existing battery from the already commercialized wearable healthcare bracelet and replaced it with the proposed self-charging system. They confirmed that the system can be applied to a low power wearable device via the NIR band.
There have been numerous platforms using solar irradiation, but the newly developed platform has more advantages because it allows conventional devices to be much more comfortable to wear and charged easily in everyday life using various irradiation sources for constant charging.
With this aspect, the proposed platform facilitates more flexible designs, which are the important component for actual commercialization. It also secures higher photostability and efficient than existing structures.
Professor Lee said, “By using the NIR band, we proposed a new approach to solve charging system issues of wearable devices. I believe that this platform will be a novel platform for energy conversion and that its application can be further extended to various fields, including mobiles, IoTs, and drones.”
This research, led by PhD Se-Woong Baek and M.S. candidate Jungmin Cho, was published in Advanced Materials on May 11.
Figure 1. a) Conceptual NIR-driven self-charging system including a flexible CQD PVs module and an interdigitatedly structured LIB. b) Photographic images of a conventional wearable healthcare bracelet and a self-charging system-integrated wearable device.
Figure 2. Illustration of the CQD PVs structure and performance of the wireless self-charging platform.
2018.10.08 View 8468 -
Flexible Piezoelectric Acoustic Sensors for Speaker Recognition
A KAIST research team led by Professor Keon Jae Lee from the Department of Material Science and Engineering has developed a machine learning-based acoustic sensor for speaker recognition.
Acoustic sensors were spotlighted as one of the most intuitive bilateral communication devices between humans and machines. However, conventional acoustic sensors use a condenser-type device for measuring capacitance between two conducting layers, resulting in low sensitivity, short recognition distance, and low speaker recognition rates.
The team fabricated a flexible piezoelectric membrane by mimicking the basilar membrane in the human cochlear. Resonant frequencies vibrate corresponding regions of the trapezoidal piezoelectric membrane, which converts voice to electrical signal with a highly sensitive self-powered acoustic sensor.
This multi-channel piezoelectric acoustic sensor exhibits sensitivity more than two times higher and allows for more abundant voice information compared to conventional acoustic sensors, which can detect minute sounds from farther distances. In addition, the acoustic sensor can achieve a 97.5% speaker recognition rate using a machine learning algorithm, reducing by 75% error rate than the reference microphone.
AI speaker recognition is the next big thing for future individual customized services. However, conventional technology attempts to improve recognition rates by using software upgrades, resulting in limited speaker recognition rates. The team enhanced the speaker recognition system by replacing the existing hardware with an innovative flexible piezoelectric acoustic sensor. Further software improvement of the piezoelectric acoustic sensor will significantly increase the speaker and voice recognition rate in diverse environments.
Professor Lee said, “Highly sensitive self-powered acoustic sensors for speaker recognition can be used for personalized voice services such as smart home appliances, AI secretaries, always-on IoT, biometric authentication, and FinTech.”
These research “Basilar Membrane-Inspired Self-Powered Acoustic Sensor” and “Machine Learning-based Acoustic Sensor for Speaker Recognition” were published in the September 2018 issue of Nano Energy.
Firgure 1: A flexible piezoelectric acoustic sensor mimicking the human cochlear.
Figure 2: Speaker recognition with a machine learning algorithm.
2018.10.04 View 7595 -
Spray Coated Tactile Sensor on a 3-D Surface for Robotic Skin
Robots will be able to conduct a wide variety of tasks as well as humans if they can be given tactile sensing capabilities.
A KAIST research team has reported a stretchable pressure insensitive strain sensor by using an all solution-based process. The solution-based process is easily scalable to accommodate for large areas and can be coated as a thin-film on 3-dimensional irregularly shaped objects via spray coating. These conditions make their processing technique unique and highly suitable for robotic electronic skin or wearable electronic applications.
The making of electronic skin to mimic the tactile sensing properties of human skin is an active area of research for various applications such as wearable electronics, robotics, and prosthetics. One of the major challenges in electronic skin research is differentiating various external stimuli, particularly between strain and pressure. Another issue is uniformly depositing electrical skin on 3-dimensional irregularly shaped objects.
To overcome these issues, the research team led by Professor Steve Park from the Department of Materials Science and Engineering and Professor Jung Kim from the Department of Mechanical Engineering developed electronic skin that can be uniformly coated on 3-dimensional surfaces and distinguish mechanical stimuli. The new electronic skin can also distinguish mechanical stimuli analogous to human skin. The structure of the electronic skin was designed to respond differently under applied pressure and strain. Under applied strain, conducting pathways undergo significant conformational changes, considerably changing the resistance. On the other hand, under applied pressure, negligible conformational change in the conducting pathway occurs; e-skin is therefore non-responsive to pressure. The research team is currently working on strain insensitive pressure sensors to use with the developed strain sensors.
The research team also spatially mapped the local strain without the use of patterned electrode arrays utilizing electrical impedance tomography (EIT). By using EIT, it is possible to minimize the number of electrodes, increase durability, and enable facile fabrication onto 3-dimensional surfaces.
Professor Park said, “Our electronic skin can be mass produced at a low cost and can easily be coated onto complex 3-dimensional surfaces. It is a key technology that can bring us closer to the commercialization of electronic skin for various applications in the near future.”
The result of this work entitled “Pressure Insensitive Strain Sensor with Facile Solution-based Process for Tactile Sensing Applications” was published in the August issue of ACS Nano as a cover article.
(Figure: Detecting mechanical stimuli using electrical impedance tomography.)
2018.09.21 View 8556 -
KAIST Develops VRFB with Longer Durability
(from left: PhD candidate Soohyun Kim, Professor Hee-Tak Kim and PhD candidate Junghoon Choi)
There has been growing demand for large-scale storage for energy produced from renewable energy sources in an efficient and stable way. To meet this demand, a KAIST research team developed a new vanadium redox-flow battery (VRFB) with 15 times greater capacity retention and five times longer durability. This VRFB battery can be an excellent candidate for a large-scale rechargeable battery with no risk of explosion.
The VRFB has received much attention for its high efficiency and reliability with the absence of cross-contamination. However, it has the limitation of having insufficient charge and discharge efficiency and a low capacity retention rate because its perfluorinated membrane is very permeable to any active materials. To minimize energy loss, it needs a membrane that has low vanadium ion permeability and high ion conductivity. Hence, there was an attempt to incorporate a hydrocarbon membrane that has low cost and high ion selectivity but it turned out that the VO₂+ caused chemical degradation, which led to shortening the battery life drastically.
To develop a membrane with pore sizes smaller than the hydrated size of vanadium ions yet larger than that of the protons, a research team co-led by Professor Hee-Tae Jung and Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering implemented a graphene-oxide framework (GOF) membrane by cross-linking graphene oxide nanosheets. They believed that GOF, having strong ion selectivity, would be a good candidate for the membrane component for the VRFB. The interlayer spacing between the GO sheets limited moisture expansion and provided selective ion permeation.
The GOF membrane increased the capacity retention of the VRFB, which showed a 15 times higher rate than that of perfluorinated membranes. Its cycling stability was also enhanced up to five times, compared to conventional hydrocarbon membranes.
These pore-sized-tuned graphene oxide frameworks will allow pore-sized tuning of membranes and will be applicable to electrochemical systems that utilize ions of various sizes, such as rechargeable batteries and sensors.
Professor Kim said, “Developing a membrane that prevents the mixing of positive and negative active materials has been a chronic issue in the field of redox-flow batteries. Through this research, we showed that nanotechnology can prevent this crossover issue and membrane degradation. I believe that this technology can be applied to various rechargeable batteries requiring large-scale storage.”
This research was published in Nano Letters on May 3.
Figure 1. Electrochemical performances of the VRFBs with Nafion 115, SPAES (sulfonated poly), and GOF/SPAES: discharge capacity
Figure 2. Schematic of the selective ion transfer of hydrated vanadium ions and protons in the GOF membrane and the molecular structure of the GOF membrane, showing that the GO nanosheets are cross-linked with EDA (ethylenediamine)
2018.09.20 View 7499 -
Using Donut-shaped Lithium Sulfide for Higher Performing Batteries
(from left: Research Professor Fangmin Ye and Professor Hee-Tak Kim)
A KAIST research team developed a lithium-sulfur battery with a doughnut-shaped active material structure showing a record lifecycle of over 600 cycles. Having higher energy density and lower production cost than a lithium-ion battery (LIB), it can be used in electric vehicles that require a longer battery life.
There has been an intense research conducted for developing lithium-sulfur batteries with high energy density because LIBs only allow for a very short travel distance per charge. However, Li-S batteries are still unable to provide a longer lifecycle due to the poor reversibility of the lithium metal cathode.
To tackle this issue, Professor Hee-Tak Kim from the Department of Chemical and Biomolecular Engineering and his team used lithium sulfide (Li₂S) cathodes and combine them with graphite anodes to enhance energy density and lifecycles for the batteries.
Yet, lithium sulfide is costly and, so far, there has not been an electrode architecture and electrolyte design that enables a longer lifecycle between the graphite anodes and lithium sulfide cathodes.
Hence, the team produced a doughnut-shaped lithium sulfide cathode active material from low-cost lithium sulfide developed from raw materials. They have also developed a lithium sulfide ion battery with a graphite anode and lithium sulfide cathode using a high concentration salt electrolyte.
This doughnut-shaped lithium sulfide showed outstanding charge and discharge reversibility through improving the transfer of lithium ions. Its highly concentrated salt electrolyte formed a stable film on the surface of the graphite electrode, which showed strong durability.
Through this technology, the team achieved 30% higher energy density than that of conventional LIBs and secured a lifecycle of more than 600 cycles. This doughnut-shaped lithium sulfide-based electrode can be manufactured using low-cost raw materials and a single heat treatment process. The electrode can also be applied to existing LIBs.
Professor Kim said, “We have demonstrated that applying low-cost sulfur compounds to LIBs can improve both energy density and the lifecycle simultaneously.”
This research, led by Research Professor Fangmin Ye, was published in Advanced Science on May 7.
Figure 1. Structural characterization of Li₂SO₄/CNT and Li₂S/CNT electrodes and suggested mechanism for the formation of the holey-Li₂S nanoarchitecture
2018.09.19 View 5769 -
Understanding Epilepsy in Pediatric Tumors; New Therapeutic Target of Intractable Epilepsy Identified
Pediatric brain tumors are characterized by frequent complications due to intractable epilepsy compared to adult brain tumors. However, the genetic cause of refractory epilepsy in pediatric brain tumors has not been elucidated yet, and it is difficult to treat patients because the tumors do not respond to existing antiepileptic drugs and debilitate children’s development.
A research team led by Professor Jeong Ho Lee of the Graduate School of Medical Science and Engineering has recently identified a neuronal BRAF somatic mutation that causes intrinsic epileptogenicity in pediatric brain tumors. Their research results were published online in Nature Medicine on September 17.
The research team studied patients’ tissue diagnosed with ganglioglioma (GG), one of the main causes of tumor-associated intractable epilepsy, and found that the BRAF V600E somatic mutation is involved in the development of neural stem cells by using deep DNA sequencing. This mutation was carried out in an animal model to reproduce the pathology of GG and to observe seizures to establish an animal model for the treatment of epileptic seizures caused by pediatric brain tumors.
Using immunohistochemical and transcriptome analysis, they realized that the BRAF V600E mutation that arose in early progenitor cells during embryonic brain formation led to the acquisition of intrinsic epileptogenic properties in neuronal lineage cells, whereas tumorigenic properties were attributed to a high proliferation of glial lineage cells exhibiting the mutation. Notably, researchers found that seizures in mice were significantly alleviated by intraventricular infusion of the BRAF V600E inhibitor, Vemurafenib, a clinical anticancer drug.
The authors said, “Our study offers the first direct evidence that the BRAF somatic mutation arising from neural stem cells plays a key role in epileptogenesis in the brain tumor. This study also showed a new therapeutic target for tumor-associated epileptic disorders.”
In collaboration with the KAIST startup company, SoVarGen, the research team is currently developing innovative therapeutics for epileptic seizures derived from pediatric brain tumors. This study was supported by the Suh Kyungbae Foundation (SUHF) and the Citizens United for Research in Epilepsy.
(Figure: Preoperative and postoperative brain MRI (left panel), tumor H&E (right upper panel) and GFAP immunohistochemical (right lower panel) staining images from a patient with ganglioglioma (GG231) carrying the BRAFV600E mutation. The white arrow and the black arrowhead indicate the brain tumor and a dysplastic neuron, respectively.)
2018.09.19 View 5747 -
Effective Drug Delivery to Heart with Tannic Acid
(Professor Haeshin Lee from the Department of Chemistry) Typical methods of drug delivery to the heart require surgical procedures involving incisions in the chest wall and bones. To efficiently treat cardiovascular and related vascular diseases without surgery, a KAIST research team developed a heart-targeting drug delivery technology using tannin acid via intravenous systemic injection. This method can be applied to the development of a variety of new protein-based drugs.
Cardiovascular-circulatory disease is currently the second leading cause of death in Korea. A typical example of this disease is myocardial infarction caused by poor oxygen and nutrient supply due to narrowed coronary arteries and poor blood flow to the heart.
Although there have been numerous research projects to develop chemotherapeutic drugs and therapeutic proteins, clinics still rely on surgical procedures. Drug delivery can be an alternative, but it is quite challenging because ceaseless dynamic cycles of the heart and massive exchanges of blood mean administered therapeutics do not stay inside the heart very long.
Professor Haeshin Lee from the Department of Chemistry and his team employed tannic acid (TA), which is known for giving bitter taste to wines. It is one of the most abundant polyphenols and can be easily found in plants, such as fruits, vegetables, cacao, and others. TA has also been used as a multifunctional coating molecule.
Using these properties of TA, the team complexed protein and peptide therapeutics with tannic acid and succeeded in targeting protein and peptide therapeutics to the heart. TA, coated on the surface of a granulated protein complex, helps maintain cardiac function because it adheres to extracellular matrices, elastin, and collagens in heart tissues allowing the protein to stay attached to the heart tissue for a longer period.
The team confirmed that these Tannic-acid-modified proteins stay in blood vessels five days longer than with protein-only injections. Additionally they found that TA-protein complexes do not show any cardiac toxicity and do not cause noticeable pathology.
The team has been continuously developing biomaterials for medical applications by testing various polyphenolic materials that feature adhesive and coating properties, including tannic acid. They have injected a mixture of TA and fibroblast growth factors (FGF) into animal models with myocardial infarctions. After four weeks, they confirmed that the infarction was reduced and the left ventricular pressure and cardiac output were almost normalized.
Professor Lee said, “Although there have been numerous drugs related to heart disease, so far there has not been efficient drug delivery to the heart so this technology will be able to reformulate existing drugs into new and more efficient drugs.”
This research, jointly led by Dr. Ki-Suk Kim from the Predictive Model Research Center, was published in Nature Biomedical Engineering on April 30 ( http://www.nature.com/articles/s41551-018-0227-9 ).
Figure 1. Schematic for the heart-targeting mechanism of TANNylated protein nanocomplexes: (1) size-dependent permeation, (2) phenolic (that is, TA), and (3) internalization by internalization by myoblasts
Figure 2. Effect of TA based protein complexes on cardiac cell transport efficiency and viral gene expression efficiency and therapeutic function in animal models with myocardial infarction
2018.09.18 View 5514 -
Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.)
A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources.
Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid
A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18.
There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways.
The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway.
In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption.
The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose.
Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.”
This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18 View 6904