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Chemobiological Platform Enables Renewable Conversion of Sugars into Core Aromatic Hydrocarbons of Petroleum
<(From Left) Professor Sun Kyu Han, Ph.D candidate Tae Wan Kim, Professor Kyeong Rok Choi, Professor Sang Yup Lee>
With growing concerns over fossil fuel depletion and the environmental impacts of petrochemical production, scientists are actively exploring renewable strategies to produce essential industrial chemicals. A collaborative research team—led by Distinguished Professor Sang Yup Lee, Senior Vice President for Research, from the Department of Chemical and Biomolecular Engineering, together with Professor Sunkyu Han from the Department of Chemistry at the Korea Advanced Institute of Science and Technology (KAIST)—has developed an integrated chemobiological platform that converts renewable carbon sources such as glucose and glycerol into oxygenated precursors, which are subsequently deoxygenated in the same solvent system to yield benzene, toluene, ethylbenzene, and p-xylene (BTEX), which are fundamental aromatic hydrocarbons used in fuels, polymers, and consumer products.
<Figure 1. Schematic representation of the chemobiological synthesis of BTEX from glucose or glycerol in Escherichia coli>
From Sugars to Aromatic Hydrocarbons of Petroleum
The researchers designed four metabolically engineered strains of Escherichia coli, each programmed to produce a specific oxygenated precursor—phenol, benzyl alcohol, 2-phenylethanol, or 2,5-xylenol. These intermediates are generated through tailored genetic modifications, such as deletion of feedback-regulated enzymes, overexpression of pathway-specific genes, and introduction of heterologous enzymes to expand metabolic capabilities.
During fermentation, the products were continuously extracted into the organic solvent isopropyl myristate (IPM). Acting as a dual-function solvent, IPM not only mitigated the toxic effects of aromatic compounds on cell growth but also served directly as the reaction medium for downstream chemical upgrading. By eliminating the need for intermediate purification, solvent exchange, or distillation, this solvent-integrated system streamlined the conversion of renewable feedstocks into valuable aromatics.
Overcoming Chemical Barriers in An Unconventional Solvent
A central innovation of this work lies in adapting chemical deoxygenation reactions to function efficiently within IPM—a solvent rarely used in organic synthesis. Traditional catalysts and reagents often proved ineffective under these conditions due to solubility limitations or incompatibility with biologically derived impurities.
Through systematic optimization, the team established mild and selective catalytic strategies compatible with IPM. For example, phenol was successfully deoxygenated to benzene in up to 85% yield using a palladium-based catalytic system, while benzyl alcohol was efficiently converted to toluene after activated charcoal pretreatment of the IPM extract. More challenging transformations, such as converting 2-phenylethanol to ethylbenzene, were achieved through a mesylation–reduction sequence adapted to the IPM phase. Likewise, 2,5-xylenol derived from glycerol was converted to p-xylene in 62% yield via a two-step reaction, completing the renewable synthesis of the full BTEX spectrum.
A Sustainable, Modular Framework
Beyond producing BTEX, the study establishes a generalizable framework for integrating microbial biosynthesis with chemical transformations in a continuous solvent environment. This modular approach reduces energy demand, minimizes solvent waste, and enables process intensification—key factors for scaling up renewable chemical production.
The high boiling point of IPM (>300 °C) simplifies product recovery, as BTEX compounds can be isolated by fractional distillation while the solvent is readily recycled. Such a design is consistent with the principles of green chemistry and the circular economy, providing a practical alternative to fossil-based petrochemical processes.
Toward A Carbon-Neutral Future
Dr. Xuan Zou, the first author of this paper, explaind, “By coupling the selectivity of microbial metabolism with the efficiency of chemical catalysis, this platform establishes a renewable pathway to some of the most widely used building blocks in the chemical industry. Future efforts will focus on optimizing metabolic fluxes, extending the platform to additional aromatic targets, and adopting greener catalytic systems.”
In addition, Distinguished Professor Sang Yup Lee noted “As the global demand for BTEX and related chemicals continues to grow, this innovation provides both a scientific and industrial foundation for reducing reliance on petroleum-based processes. It marks an important step toward lowering the carbon footprint of the fuel and chemical sectors while ensuring a sustainable supply of essential aromatic hydrocarbons.”
This research was supported by the Development of Platform Technologies of Microbial Cell Factories for the Next-Generation Biorefineries Project (2022M3J5A1056117) and the Development of Advanced Synthetic Biology Source Technologies for Leading the Biomanufacturing Industry Project (RS-2024-00399424), funded by the National Research Foundation supported by the Korean Ministry of Science and ICT. This study was published in the latest issue of the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
2025.10.13 View 2823 -
KAIST Discovers Role of Huntingtin Protein in Building the Cell Skeleton
<(From Left) Professor Ji-Joon Song, Ph.D candidate Jaesung Kim, Dr. Hyeongju Kim of KAIST’s Department of Biological Sciences>
Huntington’s disease is a rare genetic disorder and a representative neurodegenerative disease, characterized by loss of motor control, cognitive decline, and psychiatric problems. An international research team has discovered that the “huntingtin protein,” the causal protein of Huntington’s disease (whose mutations are the direct cause of the disease), also performs a new function: directly organizing the cytoskeleton, the fine structural framework inside cells. This discovery is expected to contribute not only to understanding the pathogenic mechanism of Huntington’s disease, but also to research on neurodevelopmental disorders such as Alzheimer’s disease and Parkinson’s disease, as well as muscle- or mobility-related diseases such as muscular dystrophy.
KAIST (President Kwang Hyung Lee) announced on September 30 that a research team led by Professor Ji-Joon Song of the Department of Biological Sciences, in collaboration with the Institute of Science and Technology Austria (ISTA), Sorbonne University/Paris Brain Institute, and the Swiss Federal Institute of Technology Lausanne (EPFL), has uncovered—through cryo-electron microscopy (cryo-EM) and cell biology methods—the structural principle by which the huntingtin protein arranges cytoskeletal microfilaments (F-actin) into bundles.
Until now, the huntingtin protein was known only to “use” the cytoskeleton, being involved in vesicle transport or microtubule-based transport. The team, however, demonstrated that huntingtin physically organizes the cytoskeleton itself. This study is considered the first in the world to prove this new role of the huntingtin protein at the molecular level.
The researchers confirmed that huntingtin binds directly to cytoskeletal microfilaments (F-actin), and that pairs of huntingtin proteins bundle the cytoskeleton into arrays at intervals of about 20 nanometers.
Such cytoskeletal bundles play a crucial role in the development of neural connectivity. Indeed, structural development of neurons was found to be impaired in nerve cells deficient in the huntingtin protein.
<Elucidation of the Mechanism of Cytoskeletal Microfilament Bundle Formation by Huntingtin Protein and Its Impact on Neuronal Development>
First author Jaesung Kim, a PhD candidate at KAIST, stated, “This study provides a new perspective for understanding the molecular mechanism of the huntingtin protein, the cause of an incurable disease that has long remained a mystery.”
Professor Ji-Joon Song of KAIST’s Department of Biological Sciences explained, “This achievement not only provides an important clue to understanding the pathogenic mechanism of Huntington’s disease, but is also expected to have a far-reaching impact on research into cytoskeleton-related diseases,” and added that “it opens new avenues for exploring the role of the huntingtin protein in diverse biological phenomena such as cell division, migration, and mechanical signal transduction.”
This research was conducted with Jaesung Kim (PhD candidate, KAIST), Hyeongju Kim (now at Harvard University), Rémi Carpentier (Paris Brain Institute), Mariacristina Capizzi (Paris Brain Institute), and others as co-first authors, and was published on September 19 in Science Advances, a sister journal of Science.
※ Paper title: “Structure of the Huntingtin F-actin complex reveals its role in cytoskeleton organization,” DOI: https://doi.org/10.1126/sciadv.adw4124※ Co-corresponding authors: Ji-Joon Song (KAIST), Florian Schur (ISTA), and Sandrine Humbert (Sorbonne University/Paris Brain Institute).
This research was supported by the Ministry of Health and Welfare’s Global Research Collaboration Program (Korea–Switzerland Biohealth International Joint Research) and the Korea–Austria Cooperation Program.
2025.09.30 View 3043 -
Thinking outside the box to Fabricate Customized 3D Neural Chips
<(From Left) Professor Yoonkey Nam, Dr. Dongjo Yoon from the Department of Bio and Brain Engineering>
Cultured neural tissues have been widely used as a simplified experimental model for brain research. However, existing devices for growing and recording neural tissues, which are manufactured using semiconductor processes, have limitations in terms of shape modification and the implementation of three-dimensional (3D) structures.
By "thinking outside the box," a KAIST research team has successfully created a customized 3D neural chip. They first used a 3D printer to fabricate a hollow channel structure, then used capillary action to automatically fill the channels with conductive ink, creating the electrodes and wiring. This achievement is expected to significantly increase the design freedom and versatility of brain science and brain engineering research platforms.
On the 25th, KAIST announced that a research team led by Professor Yoonkey Nam from the Department of Bio and Brain Engineering has successfully developed a platform technology that overcomes the limitations of traditional semiconductor-based manufacturing. This technology allows for the precise fabrication of "3D microelectrode array" (neural interfaces with multiple microelectrodes arranged in a 3D space to measure and stimulate the electrophysiological signal of neurons) in various customized forms for in vitro culture chips.
Existing 3D microelectrode array fabrication, based on semiconductor processes, has limited 3D design freedom and is expensive. While 3D printing-based fabrication techniques have recently been proposed to overcome these issues, they still have limitations in terms of 3D design freedom for various in vitro neural network structures because they follow the traditional sequence of "conductive material patterning → insulator coating → electrode opening."
The KAIST research team leveraged the excellent 3D design freedom provided by 3D printing technology and its ability to use printed materials as insulators. By reversing the traditional process, they established an innovative method that allows for more flexible design and functional measurement of 3D neuronal network models for in vitro culture.
<Schematic Diagram of an Integrated Cell Culture Substrate-Microelectrode Array Platform for In Vitro Cultured 3D Neural Network Models>
First, they used a 3D printer to print a hollow 3D insulator with micro-tunnels. This structure was designed to serve as a stable scaffold for conductive materials in 3D space while also supporting the creation of various 3D neuronal networks. They then demonstrated that by using capillary action to fill these internal micro-tunnels with conductive ink, they could create a 3D scaffold-microelectrode array with more freely arranged microelectrodes within a complex 3D culture support structure.
The new platform can be used to create various chip shapes, such as probe-type, cube-type, and modular-type, and supports the fabrication of electrodes using different materials like graphite, conductive polymers, and silver nanoparticles. This allows for the simultaneous measurement of multichannel neural signals from both inside and outside the 3D neuronal network, enabling precise analysis of the dynamic interactions and connectivity between neurons.
Professor Nam stated, "This research, which combines 3D printing and capillary action, is an achievement that significantly expands the freedom of neural chip fabrication." He added that it will contribute to the advancement of fundamental brain science research using neural tissue, as well as applied fields like cell-based biosensors and biocomputing.
Dr. Dongjo Yoon from KAIST's Department of Bio and Brain Engineering participated as the first author of the study. The research findings were published online in the international academic journal Advanced Functional Materials (June 25th issue).
※Paper Title: Highly Customizable Scaffold-Type 3D Microelectrode Array Platform for Design and Analysis of the 3D Neuronal Network In Vitro
This research was supported by the Consolidator Grants Program and the Global Basic Research Laboratory Program of the National Research Foundation of Korea.
2025.09.26 View 2637 -
KAIST team links early life epigenetic memory to adult brain inflammation
<(From left) Professor Won-Suk Chung, Ph.D. Ph.D candidate Hyeonji Park Dr. Seongwan Park, Professor Inkyung Jung>
Why do some people remain healthy through childhood yet become more vulnerable to brain disorders such as dementia later in life? A KAIST (President Kwang Hyung Lee) -led team has uncovered a key part of the answer: a developmental ‘switch’ in astrocytes—the brain’s most abundant support cells that shapes how strongly the brain’s immune system reacts in adulthood. The study identifies a gene, NR3C1 (encoding the glucocorticoid receptor), as a master regulator of this switch and shows how early-life epigenetic ‘memory’ can predispose the adult brain to excessive inflammation.
The work was carried out by a joint team led by Professor Inkyung Jung (Department of Biological Sciences, KAIST) and Associate Director Won-Suk Chung (Center for Vascular Research, Institute for Basic Science; Professor, KAIST Biological Sciences). Using mouse models, the researchers mapped gene-regulatory programs across multiple stages of astrocyte development and found that NR3C1 acts during a brief early-postnatal window to enforce long-term immune restraint.
<The schematic illustrates how the NR3C1 gene (glucocorticoid receptor) suppresses the immune response of astrocytes. In normal (control) astrocytes, NR3C1 binds to specific regulatory regions of DNA (nGRE) to inhibit the expression of immune-related genes, thereby maintaining brain homeostasis even under immune stimulation. In contrast, in NR3C1-deficient astrocytes (KO), this suppression is lost, leading to excessive activation of inflammation-related genes such as Gfap, Il6st, Stat2, and Cxcl10. As a result, in an autoimmune encephalomyelitis (EAE) model, pronounced neuroinflammation and clinical symptoms (paralysis and severe debilitation) are observed>
To build this map, the team combined state-of-the-art 3D epigenome profiling with RNA sequencing and chromatin accessibility analyses, capturing how DNA folds and which regulatory elements contact target genes. They identified 55 stage-specific transcription factors that guide astrocyte maturation; among them, NR3C1 emerged as the critical ‘switch’ in early life. Notably, deleting NR3C1 in astrocytes did not disrupt normal development. However, when the adult mice were challenged with an autoimmune model of multiple sclerosis, animals lacking astrocytic NR3C1 mounted exaggerated inflammatory responses and developed more severe disease.
Mechanistically, the study shows that early loss of NR3C1 epigenetically primes immune genes - keeping their regulatory elements open and ready - so that later in life these genes respond too strongly to inflammatory cues. In effect, NR3C1 serves as an early ‘brake’ that prevents over-activation of astrocyte immune programs in adulthood.
“This is the first demonstration that astrocyte immune functions are governed by epigenetic memory,” said Professor Won-Suk Chung. “Our findings offer new clues to the origins of degenerative brain disorders, including Alzheimer’s disease.”
“We reveal a temporal regulatory window in astrocyte development that can set the stage for disease vulnerability in adulthood,” added Professor Inkyung Jung. “Understanding the 3D genome logic behind these programs could open paths to therapies for immune-related brain disorders such as multiple sclerosis.”
<The figure shows the three-dimensional genome structure of astrocytes at specific gene loci, illustrating how NR3C1 regulates their expression. In normal cells, NR3C1 binds to DNA and maintains the chromatin in a closed state, thereby preventing unnecessary activation between distal regulatory elements (enhancers) and gene promoters. In contrast, when NR3C1 is absent, the chromatin becomes open, creating a state in which enhancers and genes can be more easily activated. As a result, genes such as Mxi1 are overexpressed, triggering inflammatory responses. This clearly demonstrates that NR3C1 plays an essential role in maintaining immune homeostasis by stabilizing three-dimensional gene regulatory mechanisms.>
The results of this study were published online on September 22 in the international journal Nature Communications (IF 15.7), with Dr. Seongwan Park and PhD student Hyeonji Park of KAIST’s Department of Biological Sciences as co-first authors.
※ Paper title: “NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice,” DOI: https://www.nature.com/articles/s41467-025-64088-5
In addition, on September 17, the journal published a commentary article introducing this research: https://www.nature.com/articles/s41467-025-64102-w
This research was supported by the Suh Kyungbae Science Foundation, the Ministry of Health and Welfare, the Ministry of Science and ICT, and IBS.
Glossary - Epigenetic priming: preparing genes for rapid future activation by altering chromatin without changing DNA sequence
2025.09.25 View 3569 -
Simultaneous On and Off Gene Control with Gene Scissors
<(From left to right) Dr. Soo Young Moon, KAIST Institute of Life Science,Professor Ju Young Lee, Graduate School of Engineering Biology (Adjunct Professor of Biological Sciences),Dr. Myung Hyun Noh, Korea Research Institute of Chemical Technology (KRICT),Researcher Nan-Yeong An, Department of Biological Sciences>
Turning genes on and off is like flipping a light switch, controlling whether genes in a cell are active. When a gene is turned on, the production of proteins or other substances is promoted; when it's turned off, production is suppressed. Korean researchers have gone beyond the limitations of existing CRISPR technology, which focused primarily on "off" functions, by developing the world's first innovative system that can simultaneously turn genes on and off, opening a new paradigm for the synthetic biology-based bio-industry.
A joint research team led by Professor Ju Young Lee of KAIST Graduate School of Biological Engineering (Adjunct Professor of Biological Sciences) and Dr. Myung Hyun Noh of the Korea Research Institute of Chemical Technology (KRICT), an organization under the National Research Council of Science & Technology (NST) , announced on the 21st that they have developed a new dual-mode CRISPR gene editing system that can simultaneously turn on and off desired genes in E. coli.
E. coli is a representative microorganism that is easy to experiment with and can be directly applied to industrial uses. Meanwhile, CRISPR technology is considered one of the most innovative tools in 21st-century biotechnology.
In particular, bacteria, which are the foundation of synthetic biology, have a simple structure and multiply rapidly, while also being able to produce a variety of useful substances. Therefore, gene activation in bacteria is a key technology for designing "microbial factories," and its industrial value is very high.
The core of synthetic biology is to design the genetic circuits of living organisms like programming a circuit board to perform a desired function. Just as switches are turned on and off in an electronic circuit, a technology is needed to optimize metabolic pathways by activating certain genes while suppressing others. The dual-mode gene scissors developed by the research team are the key tool that enables this precise gene regulation.
Existing CRISPR gene scissors were primarily specialized for the "off" function (repression) and were excellent at blocking gene expression, but their ability to turn genes on was very limited.
Furthermore, for CRISPR to work, a specific DNA recognition sequence (PAM, protospacer adjacent motif) is required, and the narrow range of PAM recognition in existing systems limited the scope of genes that could be controlled.
In addition, while CRISPR-based activation (CRISPRa) has been somewhat developed in eukaryotic cells (human, plant, and animal cells), there were limitations in bacteria where the "on" function did not work properly due to differences in their internal transcription regulation mechanisms.
To overcome these limitations, the research team expanded the target range to access more genes and significantly improved gene activation performance by utilizing E. coli proteins. As a result, the gene scissors, which were previously "mainly for turning off," have evolved into a system that can simultaneously control both "on" and "off."
The performance verification results of the developed system were very impressive. In gene activation experiments, expression levels increased by up to 4.9 times, and in repression experiments, they could be suppressed by up to 83%.
Even more astonishing was the ability to control two different genes simultaneously. The team successfully activated one gene by 8.6 times while simultaneously repressing another by 90%.
< (Left) The principle of the dual-mode CRISPR gene scissors. When the guide RNA (gRNA) binds to the target sequence, dxCas9-CRP either promotes (CRISPRa) or inhibits (CRISPRi) the binding of RNA polymerase near the transcription start site, precisely controlling gene expression. (Center) A large-scale screening of the entire E. coli genome is conducted to identify key regulatory targets for optimizing target substance production. The metabolic pathway for producing the target substance is then re-engineered by simultaneously regulating gene expression through activation and repression. (Right) The dual-mode CRISPR gene scissors system enables systematic redesign of cell metabolism, precise reconfiguration of gene expression, and the construction of microbial strains that can perform various functions, ultimately leading to a significant increase in target substance productivity. In this study, the dual-mode CRISPR system was applied to E. coli to demonstrate the enhanced production of 'violacein,' a purple functional biopigment with anticancer effects, and its potential for expansion to other bacterial species was also confirmed. >
To demonstrate the practicality of this technology, the research team challenged themselves to increase the production of 'violacein,' a purple pigment with anticancer properties. Through large-scale experiments on all genes of E. coli, they identified genes that help in violacein production.
As a result, production increased by 2.9 times when the 'rluC' gene, which helps protein production, was turned on, and by 3.0 times when the 'ftsA' gene, which helps cell division, was turned off. When both genes were controlled simultaneously, a greater synergistic effect was observed, achieving a remarkable 3.7-fold increase in production.
Dr. Myung Hyun Noh of KRICT stated, "Precise gene activation is now possible in bacteria," and "This will greatly contribute to the development of the synthetic biology-based bio-industry."
Professor Ju Young Lee said, "This research is a successful outcome of combining gene scissors with synthetic biology to significantly enhance the efficiency of microbial production platforms," and "The ability to control a complex genetic network with a single system presents a new research paradigm." He added, "This technology has also been confirmed to work in other bacterial species and can be utilized in various fields such as the production of biopharmaceuticals, chemicals, and fuels."
< (A) A diagram of the violacein biosynthesis pathway, a functional biopigment produced from the starting material L-tryptophan through several enzymatic reactions. Violacein is a functional substance with broad applications in various industries and research fields, including medicine, healthcare, dyes, textiles, food and beverage, and cosmetics. (B) The results of a large-scale screening of gRNAs for gene activation and repression using the dual-mode CRISPR gene scissors system confirmed a 2.9-fold increase in violacein production (mg/L) upon rluC activation and a 3.0-fold increase upon ftsA repression compared to the control group. >
The results of this research, with Dr. Soo Young Moon, a postdoctoral researcher at our university's Institute of Life Science, as the first author, were published online in 'Nucleic Acids Research,' a top-tier journal in the field of molecular biology, on August 21st.
Paper Title: Dual-mode CRISPRa/i for genome-scale metabolic rewiring in Escherichia coli
Author Information: Soo Young Moon (KAIST, First Author), Mi Ri Kim (KRICT), Nan-Yeong An (KAIST), Myung Hyun Noh (KRICT, Corresponding Author), Ju Young Lee (KAIST, Corresponding Author) (Total of 5 authors)
DOI: 10.1093/nar/gkad818
This research was supported by the joint research and development program of the Ministry of Science and ICT, the National Research Foundation of Korea, and Boston Korea.
2025.09.22 View 2168 -
World's First Quantum Computing for Lego-like Design of Porous Materials
<(From Left to Right)Professor Jihan Kim, Ph.D. candidate Sinyoung Kang, Ph.D. candidate Younghoon Kim from the Department of Chemical and Biomolecular Engineering>
Multivariate Porous Materials (MTV) are like a 'collection of Lego blocks,' allowing for customized design at a molecular level to freely create desired structures. Using these materials enables a wide range of applications, including energy storage and conversion, which can significantly contribute to solving environmental problems and advancing next-generation energy technologies. Our research team has, for the first time in the world, introduced quantum computing to solve the difficult problem of designing complex MTVs, opening an innovative path for the development of next-generation catalysts, separation membranes, and energy storage materials.
On September 9, Professor Jihan Kim's research team at our university's Department of Chemical and Biomolecular Engineering announced the development of a new framework that uses a quantum computer to efficiently explore the design space of millions of multivariate porous materials (hereafter, MTV).
MTV porous materials are structures formed by the combination of two or more organic ligands (linkers) and building block materials like metal clusters. They have great potential for use in the energy and environmental fields. Their diverse compositional combinations llow for the design and synthesis of new structures. Examples include gas adsorption, mixed gas separation, sensors, and catalysts.
However, as the number of components increases, the number of possible combinations grows exponentially. It has been impossible to design and predict the properties of complex MTV structures using the conventional method of checking every single structure with a classical computer.
The research team represented the complex porous structure as a 'network (graph) drawn on a map' and then converted each connection point and block type into qubits that a quantum computer can handle. They then asked the quantum computer to solve the problem: "Which blocks should be arranged at what ratio to create the most stable structure?"
<Figure1. Overall schematics of the quantum computing algorithm to generate feasible MTV porous materials. The algorithm consists of two mapping schemes (qubit mapping and topology mapping) to allocate building blocks in a given connectivity. Different configurations go through a predetermined Hamiltonian, which is comprised of a ratio term, occupancy term, and balance term, to capture the most feasible MTV porous material>
Because quantum computers can calculate multiple possibilities simultaneously, it's like spreading out millions of Lego houses at once and quickly picking out the sturdiest one. This allows them to explore a vast number of possibilities—which a classical computer would have to calculate one by one—with far fewer resources.
The research team also conducted experiments on four different MTV structures that have been previously reported. The results from the simulation and the IBM quantum computer were identical, demonstrating that the method "actually works well."
<Figure2. VQE sampling results for experimental structures and the structures that reproduce them, using IBM Qiskit's classical simulator. The experimental structure is predicted to be the most probable outcome of the VQE algorithm's calculation, meaning it will be generated as the most stable form of the structure.>
In the future, the team plans to combine this method with machine learning to expand it into a platform that considers not only simple structural design but also synthesis feasibility, gas adsorption performance, and electrochemical properties simultaneously.
Professor Jihan Kim said, "This research is the first case to solve the bottleneck of complex multivariate porous material design using quantum computing." He added, "This achievement is expected to be widely applied as a customized material design technology in fields where precise composition is key, such as carbon capture and separation, selective catalytic reactions, and ion-conducting electrolytes, and it can be flexibly expanded to even more complex systems in the future."
Ph.D. candidates Sinyoung Kang and Younghoon Kim of the Department of Chemical and Biomolecular Engineering participated as co-first authors in this study. The research results were published in the online edition of the international journal ACS Central Science on August 22.
Paper Title: Quantum Computing Based Design of Multivariate Porous Materials
DOI: https://doi.org/10.1021/acscentsci.5c00918
Meanwhile, this research was supported by the Ministry of Science and ICT's Mid-Career Researcher Support Program and the Heterogeneous Material Support Program.
2025.09.09 View 2581 -
KAIST Develops Smart Patch That Can Run Tests Using Sweat Instead of Blood
<(From Left) Ph.D candidate Jaehun Jeon, Professor Ki-Hun Jeong of the Department of Bio and Brain Engineering>
An era is opening where it's possible to precisely assess the body’s health status using only sweat instead of blood tests. A KAIST research team has developed a smart patch that can precisely observe internal changes through sweat when simply attached to the body. This is expected to greatly contribute to the advancement of chronic disease management and personalized healthcare technologies.
KAIST (President Kwang Hyung Lee) announced on September 7th that a research team led by Professor Ki-Hun Jeong of the Department of Bio and Brain Engineering has developed a wearable sensor that can simultaneously and in real-time analyze multiple metabolites in sweat.
Recently, research on wearable sensors that analyze metabolites in sweat to monitor the human body’s precise physiological state has been actively pursued. However, conventional “label-based” sensors, which require fluorescent tags or staining, and “label-free” methods have faced difficulties in effectively collecting and controlling sweat. Because of this, there have been limitations in precisely observing metabolite changes over time in actual human subjects.
<Figure 1. Flexible microfluidic nanoplasmonic patch (left). Sequential sample collection using the patch (center) and label-free metabolite profiling (right). In this study, we designed and fabricated a fully flexible nanoplasmonic microfluidic patch for label-free sweat analysis and performed SERS signal measurement and analysis directly from human sweat. Through this, we propose a platform capable of precisely identifying physiological changes induced by physical activity and dietary conditions.>
To overcome these limitations, the research team developed a thin and flexible wearable sweat patch that can be directly attached to the skin. This patch incorporates both microchannels for collecting sweat and an ultrafine nanoplasmonic structure* that label-freely analyzes sweat components using light. Thanks to this, multiple sweat metabolites can be simultaneously analyzed without the need for separate staining or labels, with just one patch application.
* Nanoplasmonic structure: An optical sensor structure where nanoscale metallic patterns interact with light, designed to sensitively detect the presence or changes in concentration of molecules in sweat.
The patch was created by combining nanophotonics technology, which manipulates light at the nanometer scale (one-hundred-thousandth the thickness of a human hair) to read molecular properties, with microfluidics technology, which precisely controls sweat in channels thinner than a hair.
In other words, within a single sweat patch, microfluidic technology enables sweat to be collected sequentially over time, allowing for the measurement of changes in various metabolites without any labeling process. Inside the patch are six to seventeen chambers (storage spaces), and sweat secreted during exercise flows along the microfluidic structures and fills each chamber in order.
<Figure 2. Example of the fabricated patch worn (left) and images of sequential sweat collection and storage (right). By designing precise microfluidic channels based on capillary burst valves, sequential sweat collection was implemented, which enabled label-free analysis of metabolite changes associated with exercise and diet.>
The research team applied the patch to actual human subjects and succeeded in continuously tracking the changing components of sweat over time during exercise. Previously, only about two components could be checked simultaneously through a label-free approach, but in this study, they demonstrated for the first time in the world that three metabolites—uric acid, lactic acid, and tyrosine—can be quantitatively analyzed simultaneously, as well as how they change depending on exercise and diet. In particular, by using artificial intelligence analysis methods, they were able to accurately distinguish signals of desired substances even within the complex components of sweat.
<Figure 3. Label-free analysis graphs of metabolite changes in sweat induced by exercise. Using the fabricated patch in combination with a machine learning model, metabolite concentrations in the sweat of actual subjects were analyzed. Comparison of sweat samples collected before and after consumption of a purine-rich diet, under exercise conditions, revealed label-free detection of changes in uric acid and tyrosine levels, as well as exercise-induced lactate increase. Validation experiments using commercial kits further confirmed the quantification accuracy, supporting the clinical applicability of this platform>
Professor Ki-Hun Jeong said, “This research lays the foundation for precisely monitoring internal metabolic changes over time without blood sampling by combining nanophotonics and microfluidics technologies.” He added, “In the future, it can be expanded to diverse fields such as chronic disease management, drug response tracking, environmental exposure monitoring, and the discovery of next-generation biomarkers for metabolic diseases.”
This research was conducted with Jaehun Jeon, a PhD student, as the first author and was published online in Nature Communications on August 27.
Paper Title: “All-Flexible Chronoepifluidic Nanoplasmonic Patch for Label-Free Metabolite Profiling in Sweat”
DOI: https://doi.org/10.1038/s41467-025-63510-2
This achievement was supported by the National Research Foundation of Korea, the Ministry of Science and ICT, the Ministry of Health and Welfare, and the Ministry of Trade, Industry and Energy.
2025.09.08 View 2492 -
Batteries Make 12Minute Charge for 800km Drive a Reality
<Photo 1. (From left in the front row) Dr. Hyeokjin Kwon from Chemical and Biomolecular Engineering, Professor Hee Tak Kim, and Professor Seong Su Kim from Mechanical Engineering>
Korean researchers have ushered in a new era for electric vehicle (EV) battery technology by solving the long-standing dendrite problem in lithium-metal batteries. While conventional lithium-ion batteries are limited to a maximum range of 600 km, the new battery can achieve a range of 800 km on a single charge, a lifespan of over 300,000 km, and a super-fast charging time of just 12 minutes.
KAIST (President Kwang Hyung Lee) announced on the 4th of September that a research team from the Frontier Research Laboratory (FRL), a joint project between Professor Hee Tak Kim from the Department of Chemical and Biomolecular Engineering, and LG Energy Solution, has developed a "cohesion-inhibiting new liquid electrolyte" original technology that can dramatically increase the performance of lithium-metal batteries.
Lithium-metal batteries replace the graphite anode, a key component of lithium-ion batteries, with lithium metal. However, lithium metal has a technical challenge known as dendrite, which makes it difficult to secure the battery's lifespan and stability. Dendrites are tree-like lithium crystals that form on the anode surface during battery charging, negatively affecting battery performance and stability.
This dendrite phenomenon becomes more severe during rapid charging and can cause an internal short-circuit, making it very difficult to implement a lithium-metal battery that can be recharged under fast-charging conditions.
The FRL joint research team has identified that the fundamental cause of dendrite formation during rapid charging of lithium metal is due to non-uniform interfacial cohesion on the surface of the lithium metal. To solve this problem, they developed a "cohesion-inhibiting new liquid electrolyte."
The new liquid electrolyte utilizes an anion structure with a weak binding affinity to lithium ions (Li⁺), minimizing the non-uniformity of the lithium interface. This effectively suppresses dendrite growth even during rapid charging.
This technology overcomes the slow charging speed, which was a major limitation of existing lithium-metal batteries, while maintaining high energy density. It enables a long driving range and stable operation even with fast charging.
Je-Young Kim, CTO of LG Energy Solution, said, "The four years of collaboration between LG Energy Solution and KAIST through FRL are producing meaningful results. We will continue to strengthen our industry-academia collaboration to solve technical challenges and create the best results in the field of next-generation batteries."
<Figure 1. Infographic on the KAIST-LGES FRL Lithium-Metal Battery Technology>
Hee Tak Kim, Professor from Chemical and Biomolecular Engineering at KAIST, commented, "This research has become a key foundation for overcoming the technical challenges of lithium-metal batteries by understanding the interfacial structure. It has overcome the biggest barrier to the introduction of lithium-metal batteries for electric vehicles."
The study, with Dr. Hyeokjin Kwon from the KAIST Department of Chemical and Biomolecular Engineering as the first author, was published in the prestigious journal Nature Energy on September 3.
Nature Energy: According to the Journal Impact Factor announced by Clarivate Analytics in 2024, it ranks first among 182 energy journals and 23rd among more than 21,000 journals overall.
Article Title: Covariance of interphasic properties and fast chargeability of energy-dense lithium metal batteries
DOI: 10.1038/s41560-025-01838-1
The research was conducted through the Frontier Research Laboratory (FRL, Director Professor Hee Tak Kim), which was established in 2021 by KAIST and LG Energy Solution to develop next-generation lithium-metal battery technology.
2025.09.04 View 8513 -
KAIST succeeds in controlling complex altered gene networks to restore them to normal
Previously, research on controlling gene networks has been carried out based on a single stimulus-response of cells. More recently, studies have been proposed to precisely analyze complex gene networks to identify control targets. A KAIST research team has succeeded in developing a universal technology that identifies gene control targets in altered cellular gene networks and restores them. This achievement is expected to be widely applied to new anticancer therapies such as cancer reversibility, drug development, precision medicine, and reprogramming for cell therapy.
KAIST (President Kwang Hyung Lee) announced on the 28th of August that Professor Kwang-Hyun Cho’s research team from the Department of Bio and Brain Engineering has developed a technology to systematically identify gene control targets that can restore the altered stimulus-response patterns of cells to normal by using an algebraic approach. The algebraic approach expresses gene networks as mathematical equations and identifies control targets through algebraic computations.
The research team represented the complex interactions among genes within a cell as a "logic circuit diagram" (Boolean network). Based on this, they visualized how a cell responds to external stimuli as a "landscape map" (phenotype landscape).
By applying a mathematical method called the "semi-tensor product,*" they developed a way to quickly and accurately calculate how the overall cellular response would change if a specific gene were controlled.
*Semi-tensor product: a method that calculates all possible gene combinations and control effects in a single algebraic formula
However, because the key genes that determine actual cellular responses number in the thousands, the calculations are extremely complex. To address this, the research team applied a numerical approximation method (Taylor approximation) to simplify the calculations. In simple terms, they transformed a complex problem into a simpler formula while still yielding nearly identical results.
Through this, the team was able to calculate which stable state (attractor) a cell would reach and predict how the cell’s state would change when a particular gene was controlled. As a result, they were able to identify core gene control targets that could restore abnormal cellular responses to states most similar to normal.
Professor Cho’s team applied the developed control technology to various gene networks and verified that it can accurately predict gene control targets that restore altered stimulus-response patterns of cells back to normal.
In particular, by applying it to bladder cancer cell networks, they identified gene control targets capable of restoring altered responses to normal. They also discovered gene control targets in large-scale distorted gene networks during immune cell differentiation that are capable of restoring normal stimulus-response patterns. This enabled them to solve problems that previously required only approximate searches through lengthy computer simulations in a fast and systematic way.
Professor Cho said, “This study is evaluated as a core original technology for the development of the Digital Cell Twin model*, which analyzes and controls the phenotype landscape of gene networks that determine cell fate. In the future, it is expected to be widely applicable across the life sciences and medicine, including new anticancer therapies through cancer reversibility, drug development, precision medicine, and reprogramming for cell therapy.”
*Digital Cell Twin model: a technology that digitally models the complex reactions occurring within cells, enabling virtual simulations of cellular responses instead of actual experiments
KAIST master’s student Insoo Jung, PhD student Corbin Hopper, PhD student Seong-Hoon Jang, and PhD student Hyunsoo Yeo participated in this study. The results were published online on August 22 in Science Advances, an international journal published by the American Association for the Advancement of Science (AAAS).
※ Paper title: “Reverse Control of Biological Networks to Restore Phenotype Landscapes”
※ DOI: https://www.science.org/doi/10.1126/sciadv.adw3995
This research was supported by the Mid-Career Researcher Program and the Basic Research Laboratory Program of the National Research Foundation of Korea, funded by the Ministry of Science and ICT.
2025.08.29 View 4518 -
KAIST-KBSI, ‘Communication’ Between Proteins Found to Mitigate Alzheimer’s Toxicity… Opening the Path to Treatment
50 million people worldwide are estimated to have dementia, with Alzheimer’s disease—accounting for over 70%—being the representative neurodegenerative brain disorder. A Korean research team has, for the first time in the world, identified at the molecular level that tau and amyloid-β, the two key pathological proteins of Alzheimer’s disease, directly communicate to regulate toxicity. This achievement is expected to provide new insights into the pathophysiology of Alzheimer’s disease, as well as important clues for discovering biomarkers for early diagnosis and developing therapeutics for neurodegenerative brain disorders.
KAIST (President Kwang Hyung Lee) announced on the 24th of August that Professor Mi Hee Lim’s research team in the Department of Chemistry (Director of the Research Center for Metal–Neuroprotein Interactions), in collaboration with Dr. Young-Ho Lee’s team from the Division of Advanced Biomedical Research at the Korea Basic Science Institute (KBSI, President Sung-kwang Yang) under the National Research Council of Science & Technology (NST, Chairperson Yeung-Shik Kim), together with Dr. Yun Kyung Kim and Dr. Sung Su Lim from the Brain Science Institute at the Korea Institute of Science and Technology (KIST, President Sang-Rok Oh), has elucidated at the molecular level that the microtubule-binding domain of tau—one of the major pathological proteins of Alzheimer’s disease—directly interacts with amyloid-β (tau–amyloid-β communication), alters its aggregation pathway, and alleviates cellular toxicity.
Pathologically, Alzheimer’s disease is characterized by the accumulation of“neurofibrillary tangles” formed by aggregates of tau, a protein responsible for transporting nutrients and signaling molecules within neurons, and “amyloid plaques (senile plaques)” formed by clusters of amyloid-β fragments—abnormally cleaved from amyloid precursor protein, which is involved in brain development, intercellular signaling, and neuronal recovery—that aggregate in and around neuronal membranes in the brain.
Although tau and amyloid-β form pathological structures in spatially separated locations, it has been suggested that they may coexist inside and outside of cells and potentially interact. However, the molecular-level understanding of how their direct interaction affects the onset and progression of the disease has not been clearly revealed until now.
The joint research team found that among the structural repeats of tau protein that bind to microtubules (the intracellular transport system) inside neurons—K18, R1–R4, PHF6*, and PHF6—specifically K18, R2, and R3 bind with amyloid-β to form ‘tau–amyloid-β heterocomplexes.’ This process is significant because amyloid-β normally assembles into highly toxic, rigid fibers (amyloid fibrils), but when certain tau regions bind, amyloid-β shifts to an aggregation pathway that produces less toxic, less rigid aggregates.
Notably, these repeat regions of tau delay the nucleation stage (the initial step of amyloid aggregation linked to disease onset) and simultaneously alter the aggregation speed and structural form of amyloid-β associated with disease progression. As a result, the toxicity caused by amyloid-β was markedly reduced in both the intracellular and extracellular environments of the brain.
In this study, the team combined precise analytical techniques—including spectroscopy, mass spectrometry, isothermal titration calorimetry, and nuclear magnetic resonance—with cell-based toxicity assays to comprehensively analyze the structural, thermodynamic, and functional properties of tau–amyloid interactions.
The findings revealed that specific regions of tau’s microtubule-binding repeats possess both hydrophilic (water-attracting) and hydrophobic (water-repelling) characteristics, and when the balance of these two properties is optimized, tau binds more effectively to amyloid-β. In other words, the intrinsic properties of tau determine its binding affinity with amyloid-β, its modulation of aggregation pathways, and its ability to regulate toxicity.
Dr. Young-Ho Lee of KBSI stated, “This research has uncovered a new molecular mechanism for the onset and progression of dementia, an intractable neurodegenerative disease. In particular, multidisciplinary convergent research focused on molecular interactions and protein aggregation is expected to play a pivotal role in clarifying not only the cross-talk between Alzheimer’s and Parkinson’s diseases but also the interconnections among various diseases such as dementia, diabetes, and cancer.”
Professor Mi Hee Lim of KAIST added, “Tau protein does not merely contribute to pathological formation, but rather, through specific microtubule-binding repeat structures, it exerts a molecular function that actively mitigates amyloid-β aggregation and toxicity. This provides a new turning point in the pathological understanding of Alzheimer’s disease. The significance of this study lies in identifying new molecular motifs that could serve as therapeutic targets not only for Alzheimer’s but also for a variety of protein aggregation-based neurodegenerative brain disorders.”
This research, with Dr. Min Geun Kim of KAIST’s Department of Chemistry as first author, was published on August 22 in the internationally renowned journal Nature Chemical Biology (Impact factor: 13.7, top 3.8% in the field of chemistry).
※ Paper Title: “Interactions with tau’s microtubule-binding repeats modulate amyloid-β aggregation and toxicity”
※ DOI: 10.1038/s41589-025-01987-0
This research was supported by the National Research Foundation of Korea’s Basic Research Program (Leader Research and Mid-career Researcher Program), the Sejong Science Fellowship, as well as KBSI and KIST.
2025.08.25 View 4977 -
KAIST Develops Bioelectrosynthesis Platform for Switch-Like Precision Control of Cell Signaling
<(From left)Professor Jimin Park, Ph.D candidate Myeongeun Lee, Ph.D cadidate Jaewoong Lee,Professor Jihan Kim>
Cells use various signaling molecules to regulate the nervous, immune, and vascular systems. Among these, nitric oxide (NO) and ammonia (NH₃) play important roles, but their chemical instability and gaseous nature make them difficult to generate or control externally. A KAIST research team has developed a platform that generates specific signaling molecules in situ from a single precursor under an applied electrical signal, enabling switch-like, precise spatiotemporal control of cellular responses. This approach could provide a foundation for future medical technologies such as electroceuticals, electrogenetics, and personalized cell therapies.
KAIST (President Kwang Hyung Lee) announced on August 11 that a research team led by Professor Jimin Park from the Department of Chemical and Biomolecular Engineering, in collaboration with Professor Jihan Kim's group, has developed a 'Bioelectrosynthesis Platform' capable of producing either nitric oxide or ammonia on demand using only an electrical signal. The platform allows control over the timing, spatial range, and duration of cell responses.
Inspired by enzymes involved in nitrite reduction, the researchers implemented an electrochemical strategy that selectively produces nitric oxide or ammonia from a single precursor, nitrite (NO₂⁻). By changing the catalyst, the team generated ammonia or nitric oxide from nitrite using a copper-molybdenum-sulfur catalyst (Cu2MoS4) and an iron-incorporated catalyst (FeCuMS4), respectively.
Through electrochemical measurements and computer simulations, the team revealed that Fe sites in the FeCuMoS4 catalyst bind nitric oxide intermediates more strongly, shifting product selectivity toward nitric oxide. Under the same electrical conditions, the Fe-containing catalyst preferentially produces nitric oxide, whereas the Cu2MoS4 catalyst favors ammonia production.
<Figure 1. Schematic diagram of a bio-electrosynthesis platform that synthesizes a desired signaling substance with an electrical signal (left) and the results of precise cell control using it (right)>
The research team demonstrated biological functionality by using the platform to activate ion channels in human cells. Specifically, electrochemically produced nitric oxide activated TRPV1 channels (responsive to heat and chemical stimuli), while electrochemically produced ammonia induced intracellular alkalinization and activated OTOP1 proton channels. By tuning the applied voltage and electrolysis duration, the team modulated the onset time, spatial extent, and termination of cellular responses, which effectively turned cellular signaling on and off like a switch.
<Figure 2. Experimental results showing the change in the production ratio of nitric oxide and ammonia signaling substances according to the type of catalyst (left) and computational simulation results showing the strong bond between iron and nitric oxide (right)>
Professor Jimin Park said, "This work is significant because it enables precise cellular control by selectively producing signaling molecules with electricity. We believe it has strong potential for applications in electroceutical technologies targeting the nervous system or metabolic disorders."
Myeongeun Lee and Jaewoong Lee, Ph.D. students in the Department of Chemical and Biomolecular Engineering at KAIST, served as the co-first authors. Professor Jihan Kim is a co-author. The paper was published online in 'Angewandte Chemie International Edition' on July 8, 2025 (DOI: 10.1002/ange.202508192).
Reference: https://doi.org/10.1002/ange.202508192
Authors: Myeongeun Lee†, Jaewoong Lee†, Yongha Kim, Changho Lee, Sang Yeon Oh, Prof. Jihan Kim, Prof. Jimin Park*
†These authors contributed equally. *Corresponding author.
2025.08.12 View 4005 -
Prof. Seungbum Koo’s Team Receives Clinical Biomechanics Award at the 30th International Society of Biomechanics Conference
<(From Left) Ph.D candidate Jeongseok Oh from KAIST, Dr. Seungwoo Yoon from KAIST, Prof.Joon-Ho Wang from Samsung Medical Center, Prof.Seungbum Koo from KAIST>
Professor Seungbum Koo’s research team received the Clinical Biomechanics Award at the 30th International Society of Biomechanics (ISB) Conference, held in July 2025 in Stockholm, Sweden. The Plenary Lecture was delivered by first author and Ph.D. candidate Jeongseok Oh. This research was conducted in collaboration with Professor Joon-Ho Wang’s team at Samsung Medical Center.
Residual Translational and Rotational Kinematics After Combined ACL and Anterolateral Ligament Reconstruction During Walking
Jeongseok Oh, Seungwoo Yoon, Joon-Ho Wang, Seungbum Koo
The study analyzed gait-related knee joint motion using high-speed biplane X-ray imaging and three-dimensional kinematic reconstruction in 10 healthy individuals and 10 patients who underwent ACL reconstruction with ALL augmentation. The patient group showed excessive anterior translation and internal rotation, suggesting incomplete restoration of normal joint kinematics post-surgery. These findings provide mechanistic insight into the early onset of knee osteoarthritis often reported in this population.'
The ISB conference, held biennially for over 60 years, is the largest international biomechanics meeting. This year, it hosted 1,600 researchers from 46 countries and featured over 1,400 presentations. The Clinical Biomechanics Award is given to one outstanding study selected from five top-rated abstracts invited for full manuscript review. The winning paper is published in Clinical Biomechanics, and the award includes a monetary prize and a Plenary Lecture opportunity.
From 2019 to 2023, Koo and Wang’s teams developed a system with support from the Samsung Future Technology Development Program to track knee motion in real time during treadmill walking, using high-speed biplane X-rays and custom three-dimensional reconstruction software. This system, along with proprietary software that precisely reconstructs the three-dimensional motion of joints, was approved for clinical trials by the Ministry of Food and Drug Safety and installed at Samsung Medical Center. It is being used to quantitatively analyze abnormal joint motion patterns in patients with knee ligament injuries and those who have undergone knee surgery.
Additionally, Jeongseok Oh was named one of five finalists for the David Winter Young Investigator Award, presenting his work during the award session. This award recognizes promising young researchers in biomechanics worldwide.
2025.08.10 View 3610