KAIST Develops Self-Regenerating Catalyst That Restores Its Own Performance, Opening a Breakthrough for CO₂ Conversion Technology
<(From Left) Professor Dong Young Chung, Ph.D Candidate Hongmin An, Hanjoo Kim>
Technologies that convert carbon dioxide (CO₂) emitted from factories and power plants into useful chemical feedstocks are considered key to achieving carbon neutrality. However, rapid degradation of catalyst performance has long hindered commercialization. KAIST researchers have now developed a “self-regenerating” catalyst that restores its activity during operation, offering a potential solution to this challenge.
KAIST (President Kwang Hyung Lee) announced on the 11th of March that a research team led by Professor Dong Young Chung from the Department of Chemical and Biomolecular Engineering has identified the fundamental cause of catalyst degradation in electrochemical reactions that convert CO₂ into useful materials and has developed a new design strategy that allows catalysts to maintain their active state during the reaction.
<Schematic Illustration of Copper Catalyst Reconstruction>
The research team focused particularly on copper (Cu) catalysts, which are widely used in CO₂ conversion reactions. Copper catalysts are known not to simply degrade during reactions but instead undergo a process called surface reconstruction, in which their surface structure continuously changes. The study revealed that the performance and lifetime of the catalyst vary significantly depending on how this reconstruction occurs.
The researchers discovered that copper catalyst reconstruction occurs mainly through two different mechanisms. The first involves formation and reduction of oxide layers on the catalyst surface. While this temporarily increases catalytic activity, it ultimately leads to long-term degradation of catalyst performance.
The second mechanism involves partial dissolution of the catalyst metal into the electrolyte followed by redeposition onto the catalyst surface. During this process, new reactive sites—known as active sites—are continuously created on the catalyst surface.
Based on this mechanism, the team proposed a method that allows the catalyst to maintain its active state during the reaction. By introducing a trace amount of copper ions into the electrolyte, dissolution and redeposition of copper occur in a balanced cycle on the catalyst surface. This continuous cycle generates new active sites, enabling the catalyst to maintain stable performance over extended periods.
Importantly, this technology can be implemented without complex additional processes or high-voltage conditions, significantly reducing energy consumption while enabling stable production of high-value C₂ compounds such as ethylene and ethanol. C₂ compounds are molecules containing two carbon atoms and are industrially important chemicals used as feedstocks for plastics, fuels, and other materials.
This research is significant because it proposes a new design concept in which catalysts are not merely optimized at the initial stage but are engineered to maintain their optimal state throughout the reaction process. The concept is expected to be applicable not only to CO₂ conversion technologies but also to a wide range of electrochemical energy conversion systems.
Professor Dong Young Chung stated, “This research approached catalyst degradation not as an inevitable phenomenon but as a controllable process,” adding, “We proposed a new strategy that allows catalysts to continuously maintain optimal activity during the reaction.”
The study was led by Hanjoo Kim, a doctoral student at KAIST, and Hongmin An, a combined master’s-doctoral student, as co-first authors. The research was published online on February 5 in the Journal of the American Chemical Society (JACS), one of the world’s most prestigious journals in chemistry.
※ Paper title: “Dynamic Interface Engineering via Mechanistic Understanding of Copper Reconstruction in Electrochemical CO₂ Reduction Reaction” DOI: 10.1021/jacs.5c16244
This research was supported by the Global Young Connect Program for Materials and the National Strategic Materials Technology Development Program funded through the National Research Foundation of Korea.
KAIST Develops mRNA Platform That Remains Effective Even in Aging and Obesity
<(From Left) Dr. Subin Yoon, Ph.D candidate Hyeonggon Cho, Prof. Jae-Hwan Nam, Prof. Young-suk Lee>
Since the COVID-19 pandemic, mRNA vaccines have gained attention as a next-generation pharmaceutical technology. mRNA therapeutics work by delivering genetic instructions that enable cells to produce specific proteins for therapeutic effects. However, their efficacy has been reported to decline in elderly individuals or patients with obesity. To address this limitation, Korean researchers have newly designed a key regulatory region of mRNA that improves therapeutic protein production efficiency, developing a next-generation mRNA platform that maintains effectiveness even in aging and obesity conditions.
KAIST (President Kwang Hyung Lee) announced on the 10th of March that a joint research team led by Professor Young-suk Lee of the Department of Bio and Brain Engineering and Professor Jae-Hwan Nam of The Catholic University of Korea (President Jun-Gyu Choi) has developed a new mRNA platform by precisely designing the sequence of the 5′ untranslated region (5′UTR)*, a key regulatory region of mRNA.*5′ untranslated region (5′UTR): A region of mRNA that initiates and regulates protein production. The design of this region influences both the amount and speed of protein synthesis.
The research team analyzed large-scale bioinformatics datasets to identify 5′UTR sequences that enable proteins to be produced more efficiently across diverse cellular environments. When applied, the designed sequences significantly enhanced protein production and immune responses even in preclinical models of aging and obesity.
mRNA is a long single-stranded RNA molecule that serves as the blueprint for producing proteins required by the body. It consists of several components: the 5′UTR, which initiates and regulates the rate of protein production; the coding sequence (CDS), which contains the genetic information for a specific protein; the 3′ untranslated region (3′UTR), which helps maintain mRNA stability within cells; and the poly(A) tail, which further enhances stability and supports protein synthesis.
Among these components, the 5′UTR and 3′UTR do not determine the type of protein produced, but they play a critical role in regulating how efficiently the protein is synthesized. For this reason, these regions are receiving increasing attention as key bioengineering platforms for improving the performance of various mRNA therapeutics, including vaccines and treatments.
<Schematic Diagram of mRNA Therapeutic Design and Validation Using Bioinformatics>
To identify highly efficient 5′UTR sequences capable of promoting protein production across multiple tissues and cellular environments, the team conducted an integrated analysis of large-scale biological datasets. This included multiple analytical approaches such as RNA sequencing (RNA-seq) for analyzing gene activity across tissues, single-cell RNA sequencing (scRNA-seq) for examining gene expression at the individual cell level, and ribosome profiling (Ribo-seq) for measuring actual protein translation efficiency.
The researchers also focused on the fact that in aging or obesity conditions, cells often experience high levels of stress—particularly oxidative stress—which can reduce their ability to synthesize proteins. When the newly designed mRNA therapeutics were applied to preclinical models of aging and obesity, the results showed significantly improved protein production and immune responses compared with existing approaches. This research is expected to be applicable not only to mRNA vaccines but also to a wide range of biopharmaceutical technologies, including gene therapies and immunotherapies.
<Multimodal Bio–Big Data Analysis–Based mRNA Therapeutic Design (AI-Generated Image)>
Professor Young-suk Lee of KAIST Department of Bio and Brain Engineering stated, “This study identified a design strategy that enables mRNA to produce proteins more efficiently by analyzing large-scale biological data,” adding, “This technology will provide an important foundation for ensuring that mRNA vaccines and therapeutics remain effective even in environments where drug efficacy may decline, such as in elderly or obese patients.”
In this study, Dr. Subin Yoon from The Catholic University of Korea and doctoral candidate Hyeonggon Cho from KAIST participated as co-first authors. The research findings were published online on January 2 in the internationally renowned journal Molecular Therapy (IF = 12.0), a leading journal in gene and cell therapy.
(Paper title: ”Designing 5′UTR sequences improves the capacity of mRNA therapeutics in preclinical models of aging and obesity” DOI: https://doi.org/10.1016/j.ymthe.2025.12.060)
This research was supported by the Excellent Young Researcher Program and the Bio-Medical Technology Development Program of the National Research Foundation of Korea funded by the Ministry of Science and ICT, the Infectious Disease Response Innovative Technology Support Program of the Ministry of Food and Drug Safety, and the Infectious Disease Prevention and Therapeutics Technology Development Program of the Korea Health Industry Development Institute.
Distinguished Professor Sang Yup Lee, Senior Vice President for Research, to Lead Industry-Academic-Research Cooperation in Synthetic Biology
< Sang Yup Lee, Senior Vice President for Research at KAIST (Inaugural Chairman of the Korea Synthetic Biology Association) >
KAIST announced on February 27th that Sang Yup Lee, Distinguished Professor of the Department of Chemical and Biomolecular Engineering and Senior Vice President for Research, has been appointed as the inaugural chairman of the Korea Synthetic Biology Association (KSBA). This appointment was officially ratified during the association's 5th regular general meeting held on the 23rd.
The KSBA is a specialized consultative body established to promote cooperation in policy, industry, and research within the field of synthetic biology. Based on a network spanning industry, academia, research institutes, and government, the association supports the creation of a synthetic biology ecosystem as a national strategic technology and strengthens industrial competitiveness. It has contributed to the expansion of the domestic synthetic biology foundation through multifaceted activities such as policy proposals, international cooperation, human resource development, and industrial vitalization.
Through this appointment of the inaugural chairman, the association has established a unified leadership system and is set to formalize the operational foundation in line with the enforcement of the "Synthetic Biology Promotion Act."
At the general meeting, the 2025 business performance report was presented, and agendas for the ratification of the next chairman and the appointment of executives were resolved. Officials from the Ministry of Science and ICT also attended, expressing expectations for the association’s political role and future direction.
During the meeting, the ratification of Chairman Sang Yup Lee, who was elected by the Board of Directors in accordance with the articles of incorporation, was finally approved. Chairman Sang Yup Lee is a world-leading researcher who has pioneered the fields of synthetic biology and biotechnology. As the Senior Vice President for Research at KAIST, Head of the Metabolic Engineering National Research Laboratory, and Director of both the BioProcess Engineering Research Center and the Center for Synthetic Biology, he has led research innovation and the expansion of global cooperation. With this ratification, the KSBA has officially launched an integrated leadership system encompassing the establishment of mid-to-long-term strategies, strengthening industry-research links, and expanding global networks.
< Group photo of the Korea Synthetic Biology Association General Meeting (Chairman Sang Yup Lee, 5th from the bottom left) >
Chairman Sang Yup Lee stated, "Synthetic biology is a key strategic technology that will determine national competitiveness. We will ensure close cooperation between industry, academia, research, and government so that the purpose of laws and systems can lead to practical innovation in research and industrial fields."
Furthermore, the Board of Directors approved the appointment of directors and external auditors to enhance the accountability and transparency of organizational management, including Steering Committee Secretary Lee Seung-koo (Korea Research Institute of Bioscience and Biotechnology), as well as Park Han-oh (Bioneer), Kim장성 (Korea Research Institute of Bioscience and Biotechnology), Kim Dong-myung (Chungnam National University), Oh Min-kyu (Korea University), Cho Byung-kwan (KAIST), Yoon Hye-sun (Hanyang University), and Lee Do-heon (KAIST).
At this general meeting, the major contents of the "Synthetic Biology Promotion Act," scheduled for enforcement on April 23, and the corresponding legislative notice of the enforcement decree were shared. Prior to the enforcement of the law, the Ministry of Science and ICT prepared an enforcement decree specifying delegated matters and has been conducting a legislative notice for 40 days starting February 23. The enforcement decree includes: ▲Clarification of procedures for establishing the Basic Plan for Synthetic Biology Promotion and annual implementation plans ▲Establishment of standards for designating and operating research hubs and biofoundries ▲Materialization of safety management systems and inspection procedures.
The KSBA plans to actively pursue implementation strategies for each division so that the legislative intent of the enforcement decree can be practically realized in industrial and research fields.
The Policy and System Division will strengthen its policy advisory function to ensure that field opinions are reflected in the process of establishing basic and annual implementation plans. It will also continue to present directions for synthetic biology development and social infrastructure construction strategies through the ‘KSBA Policy Insight 2026’ report.
The Convergence Division aims to advance research systems based on data, AI, and automation to simultaneously secure research reliability and efficiency. It will also support the strengthening of technology standardization and safety management capabilities through the publication of convergence technology trend reports and the operation of workshops.
The Technology and Industry Division plans to specify industry-research linkage models that meet the standards for designating and operating research infrastructure such as biofoundries. It will also expand corporate cooperation networks to ensure that the implementation of the system leads to technology commercialization and manufacturing innovation.
The Education and Network Division will prepare a competition (IDEA-B) to discover next-generation talent and strengthen safety and ethics education to increase the accountability and expertise of synthetic biology research. Additionally, it plans to expand international cooperation to ensure that domestic systems harmonize with global norms.
The KSBA plans to further enhance the stability of organizational operations through this general meeting and expand its role as a hub institution connecting policy, industry, and research. In particular, under the unified leadership centered on Chairman Sang Yup Lee, it intends to serve as a bridge for private-public cooperation so that the intent of the "Synthetic Biology Promotion Act" can be practically implemented in the field.
< KSBA Policy Insight 2026 Report of the Korea Synthetic Biology Association >
Opening of KAIST Bio Square in Osong, a Key Hub for K-Bio
< Bird’s-Eye View of KAIST BioSquare >
KAIST is embarking on a full-scale journey in Osong, Chungcheongbuk-do, to leap forward as a world-class bio-medical hub.
The university announced that it will hold the opening ceremony for ‘KAIST Bio Square’ on the 6th at the Chungbuk Cosmetic Clinical Research Support Center, in collaboration with Chungcheongbuk-do Province and Cheongju City.
KAIST Bio Square is a core hub for the creation of 'K-Bio Square' and serves as a convergence research and education platform that breaks down the boundaries between various disciplines such as AI, physics, and mechanical engineering, centered on bio-technology. Using this as a strategic outpost, KAIST plans to establish a cooperation system with Seoul National University Hospital, Chungbuk National University Hospital, the Korea Research Institute of Bioscience and Biotechnology, and the Osong Medical Innovation Foundation to create innovative achievements in the field of R&D for aging, including the development of treatments for Parkinson's disease and medical devices.
Furthermore, it plans to attract startups that will lead innovation in the future bio-industry and develop the related industrial ecosystem, while fostering it as a bio-entrepreneurship outpost that concentrates KAIST's startup capabilities, which produce 120 venture companies annually.
The opening ceremony will be attended by major figures from industry, academia, research, and hospitals, including Young Hwan Kim, Governor of Chungcheongbuk-do; Kwang Hyung Lee, President of KAIST; Yeon Hee Lee, Member of the National Assembly; Daesoo Kim, Dean of the KAIST College of Life Science and Bioengineering; Yong Jin Kim, Vice President of Research at Seoul National University Hospital; Sang Bae Han, Dean of the College of Pharmacy at Chungbuk National University; Kyu Sun Lee, Head of the Research Division at the Korea Research Institute of Bioscience and Biotechnology; and Myung Soo Lee, Chairman of the Osong Medical Innovation Foundation.
The building where KAIST Bio Square is located (formerly the Chungbuk Cosmetic Clinical Research Support Center) consists of one basement level and three floors above ground, with the first floor currently being used as a seminar room and networking space. Starting in June, the entire building will be remodeled to create a state-of-the-art research and education space equipped with lecture rooms, faculty research offices, graduate department offices, and open labs.
Young Hwan Kim, Governor of Chungcheongbuk-do, stated, “K-Bio Square consists of three major pillars: the KAIST Osong Bio-Medical Campus Town, the Seoul National University Hospital R&D Clinical Hospital, and R&D involving the Korea Research Institute of Bioscience and Biotechnology and the Osong Medical Innovation Foundation. KAIST Bio Square will be the strategic base for realizing this.” He added, “I am grateful to KAIST President Kwang Hyung Lee and Dean Daesoo Kim of the College of Life Science and Bioengineering for their major decision.”
Kwang Hyung Lee, President of KAIST, remarked, “K-Bio Square is an important project being promoted as part of the national bio-strategy and mid-to-long-term national tasks.” He stated, “We will focus all of KAIST’s capabilities to ensure that the Osong Bio-Medical Campus Town can settle in early.” He also plans to propose cooperation measures for future medical innovation, such as the establishment of an AI healthcare graduate school with Seoul National University Hospital and Chungbuk National University Hospital, and the joint development of physician-scientist training programs.
Daesoo Kim, Dean of the KAIST College of Life Science and Bioengineering, said, “This opening is a practical fruition of the open innovation strategies that KAIST has been pursuing, such as R&D planning, the attraction of global bio-labs, and joint responses to innovative regulation-free zones.” He added, “We will lead drug development and brain/anti-aging research here to create an AI-bio innovation ecosystem where industry, academia, research, and hospitals coexist.”
Discovery of a Switch to Halt Adipocyte Generation
< (From left) Dr. Ju-Gyeong Kang, Ph.D candidate TaeJun Seol, Professor Dae-Sik Lim >
Metabolic diseases such as obesity, fatty liver, and insulin resistance are rapidly increasing worldwide, but fundamental methods to regulate the process of fat formation remain limited. In particular, once adipocytes (fat cells) are formed, they are difficult to reduce, making treatment challenging. Amidst this, a research team from our university has discovered the existence of a ‘switch’ that prevents fat formation. This discovery elucidates how an ‘epigenetic switch’—which regulates gene activity without altering the DNA sequence itself—functions during the process of adipogenesis, presenting new possibilities for the precise control of obesity and metabolic diseases in the future.
The research team, led by Professor Dae-Sik Lim and Professor Ju-Gyeong Kang from KAIST’s Department of Biological Sciences, announced on January 25th that they have identified ‘YAP/TAZ,’ key regulators of the Hippo signaling pathway*, as playing the role of an ‘epigenetic differentiation inhibition switch’ during the process of adipocyte differentiation**. The team proposed a new mechanism in which YAP/TAZ extensively inhibits the activation of genes responsible for adipocyte formation through its downstream target, ‘VGLL3.’ *Hippo signaling pathway: A cellular control system that regulates when cells grow, stop dividing, and differentiate. **Adipocyte differentiation: The process by which preadipocytes (or stem cells) transform into mature adipocytes.
Cell differentiation is not a simple matter of a single gene turning on or off; it is a complex, organic process involving multiple genes and DNA regulatory regions. The research team tracked the entire process of preadipocytes* differentiating into adipocytes using Next-Generation Sequencing (NGS), which allows for the simultaneous analysis of gene expression changes and epigenetic modifications. *Preadipocyte: A developing intermediate-stage cell whose direction as to which cell it will become has already been determined.
As a result, they confirmed that under conditions where YAP/TAZ is activated, the genetic program that establishes adipocyte identity fails to operate, and the overall adipocyte differentiation network—centered around PPARγ*—is suppressed. *PPARγ: The ‘metabolic master switch’ regulator that controls energy storage and utilization in the body.
Specifically, through single-cell analysis of adipose tissue, the research team identified VGLL3 as a novel target gene of YAP/TAZ. While it was previously known that YAP/TAZ directly binds to and inhibits PPARγ, this study revealed that VGLL3 indirectly controls the entire adipocyte differentiation program by suppressing ‘enhancers,’ which are the DNA regulatory regions of adipocyte genes. This signifies that the Hippo signaling pathway plays a crucial role in regulating the core timing that determines when and how robustly fat cells are created.
Dysfunction of adipose tissue is deeply linked to various metabolic diseases such as obesity, insulin resistance, and fatty liver. The research team expects that further studies on how the YAP/TAZ–VGLL3–PPARγ axis regulatory principle involves adipocyte formation and functional abnormalities will provide new clues for regulating or treating metabolic diseases.
< Schematic Diagram of Adipocyte Gene Regulation >
Professor Dae-Sik Lim stated, “This study is the first to establish that adipocyte differentiation is precisely controlled at the epigenetic level, beyond simple gene regulation. It has laid an important foundation for a more sophisticated understanding of the mechanisms behind adipocyte identity changes and, in the long term, for developing personalized treatment strategies for patients with metabolic diseases.”
This research, with Ph.D. student TaeJun Seol and Dr. Ju-Gyeong Kang as co-first authors, was published on January 14th in the world-renowned international academic journal, Science Advances. ※ Paper Title: YAP/TAZ-VGLL3 governs adipocyte fate via epigenetic reprogramming of PPARγ and its target enhancers, DOI: 10.1126/sciadv.aea7235
Meanwhile, this research was conducted with support from the Leader Researcher Support Program and the Overseas Excellent Scientist Recruitment Program of the National Research Foundation of Korea, funded by the Ministry of Science and ICT.
KAIST Awakens dormant immune cells inside tumors to attack cancer
<(From Left) Professor Ji-Ho Park, Dr. Jun-Hee Han from the Department of Bio and Brain Engineering>
Within tumors in the human body, there are immune cells (macrophages) capable of fighting cancer, but they have been unable to perform their roles properly due to suppression by the tumor. KAIST researchers have overcome this limitation by developing a new therapeutic approach that directly converts immune cells inside tumors into anticancer cell therapies.
KAIST (President Kwang Hyung Lee) announced on the 30th that a research team led by Professor Ji-Ho Park of the Department of Bio and Brain Engineering has developed a therapy in which, when a drug is injected directly into a tumor, macrophages already present in the body absorb it, produce CAR (a cancer-recognizing device) proteins on their own, and are converted into anticancer immune cells known as “CAR-macrophages.”
Solid tumors—such as gastric, lung, and liver cancers—grow as dense masses, making it difficult for immune cells to infiltrate tumors or maintain their function. As a result, the effectiveness of existing immune cell therapies has been limited.
CAR-macrophages, which have recently attracted attention as a next-generation immunotherapy, have the advantage of directly engulfing cancer cells while simultaneously activating surrounding immune cells to amplify anticancer responses.
However, conventional CAR-macrophage therapies require immune cells to be extracted from a patient’s blood, followed by cell culture and genetic modification. This process is time-consuming, costly, and has limited feasibility for real-world patient applications.
To address this challenge, the research team focused on “tumor-associated macrophages” that are already accumulated around tumors.
They developed a strategy to directly reprogram immune cells in the body by loading lipid nanoparticles—designed to be readily absorbed by macrophages—with both mRNA encoding cancer-recognition information and an immunostimulant that activates immune responses.
In other words, in this study, CAR-macrophages were created by “directly converting the body’s own macrophages into anticancer cell therapies inside the body.”
<Figure . Schematic illustration of the strategy for in vivo CAR-macrophage generation and cancer cell eradication via co-delivery of CAR mRNA and immunostimulants using lipid nanoparticles (LNPs)>
When this therapeutic agent was injected into tumors, macrophages rapidly absorbed it and began producing proteins that recognize cancer cells, while immune signaling was simultaneously activated. As a result, the generated “enhanced CAR-macrophages” showed markedly improved cancer cell–killing ability and activated surrounding immune cells, producing a powerful anticancer effect.
In animal models of melanoma (the most dangerous form of skin cancer), tumor growth was significantly suppressed, and the therapeutic effect was shown to have the potential to extend beyond the local tumor site to induce systemic immune responses.
Professor Ji-Ho Park stated, “This study presents a new concept of immune cell therapy that generates anticancer immune cells directly inside the patient’s body,” adding that “it is particularly meaningful in that it simultaneously overcomes the key limitations of existing CAR-macrophage therapies—delivery efficiency and the immunosuppressive tumor environment.”
This research was led by Jun-Hee Han, Ph.D., of the Department of Bio and Brain Engineering at KAIST as the first author, and the results were published on November 18 in ACS Nano, an international journal in the field of nanotechnology.
※ Paper title: “In Situ Chimeric Antigen Receptor Macrophage Therapy via Co-Delivery of mRNA and Immunostimulant,” Authors: Jun-Hee Han (first author), Erinn Fagan, Kyunghwan Yeom, Ji-Ho Park (corresponding author), DOI: 10.1021/acsnano.5c09138
This research was supported by the Mid-Career Researcher Program of the National Research Foundation of Korea.
Mathematicians Solve Cellular Noise, a Long-standing Challenge in Biology
< (From left) Researcher Dongju Lim, Researcher Seokhwan Moon, Professor Jae Kyoung Kim (KAIST), Professor Jinsu Kim (POSTECH), Professor Byung-Kwan Cho (KAIST) >
Why does cancer sometimes recur even after successful treatment, or why do some bacteria survive despite the use of powerful antibiotics? One of the key culprits identified is "Biological Noise"—random fluctuations occurring inside cells. Even when cells share the same genes, the amount of protein varies in each, creating "outliers" that evade drug treatments and survive. Until now, scientists could only control the average values of cell populations; controlling the irregular variability of individual cells remained a long-standing challenge.
A joint research team—led by Professor Jae Kyoung Kim (Department of Mathematical Sciences, KAIST), Professor Jinsu Kim (Department of Mathematics, POSTECH), and Professor Byung-Kwan Cho (Graduate School of Engineering Biology, KAIST)—has theoretically established a "Noise Control Principle." Through mathematical modeling, they have found a way to eliminate biological noise and precisely govern cellular destiny. This achievement in securing precision control technology at the single-cell level is expected to be a new milestone in solving challenges in cancer treatment and synthetic biology.
While cells in our bodies strive to maintain homeostasis for survival, their internal environments are constantly changing. Existing genetic circuit technologies could regulate the average protein levels of a cell population but often ended up amplifying the "noise"—the variance between individual cells. The research team compared this to a "shower that fluctuates between boiling and freezing." Even if the average water temperature is set to 40°C, a normal shower is impossible if the water alternates between scalding and icy. Similarly, a small number of cells that escape control due to this "trap of the average" become the primary cause of cancer recurrence or antibiotic resistance. To solve this, the team devised a new mathematical model called the "Noise Controller (NC)."
The researchers first investigated whether they could control the variance of outputs—which differs from cell to cell—using a "dimerization reaction," where the final products of a system bind together to form pairs. In the process, they confirmed that the dimerization reaction could act as a sensor to detect fluctuations (noise) in the cellular state. However, initial attempts showed that this method alone had limits in reducing differences between cells. Consequently, they determined that a device was needed to immediately reduce substances if they were overproduced. They combined this with a "degradation-based actuation" principle, which promptly breaks down proteins when they become excessive. As a result, they theoretically implemented "Noise Robust Perfect Adaptation (Noise RPA)," which maintains a constant noise level despite external environmental changes. Through this, they succeeded in suppressing cell-to-cell deviation to a Fano factor of 1—the minimum level achievable by universal biological systems.
< Figure 1. Conceptual Diagram of Noise Controller (NC) Effects: When no control technology is used (top, gray), the average value of the cell population changes due to external stimuli. With existing control technology (middle, blue), the average value is maintained, but the deviation between individual cells (noise) remains large. In contrast, using the Noise Controller (bottom, green) maintains the average while also reducing the noise level of individual cells. >
The research team proved the model's performance by virtually applying it to the DNA repair system of E. coli. In the existing system, the amount of DNA-repairing proteins varied so greatly between cells that approximately 20% of the cells failed to repair and died. However, by applying the Noise Controller (NC) to unify protein levels across all cells, the mortality rate was slashed to 7%. The team significantly boosted cell survival rates through sophisticated mathematical principles alone. This is highly significant as it moves beyond the "average control" paradigm to realize "single-cell control," dealing with each cell with precision.
< Figure 2. Structure of the Noise Controller (NC).In the conventional control scheme (left), the final output (X2) produces one of the controller proteins (Z2), and this protein is degraded together with the other controller protein (Z1) that generates the system input (X1).In contrast, the noise controller (NC) established in this study (right) has a largely similar structure, but is characterized by the production of the controller protein (Z4) through a dimerization reaction of the final output. This protein directly degrades the system input (X1).Through this mechanism, mathematical expressions for the mean of the final output (lower left equation) and its noise (lower right equation) can be derived >
Professor Jae Kyoung Kim, who led the research, stated, "The significance lies in bringing cellular noise—which was previously dismissed as luck or coincidence in biological phenomena—into the realm of controllable factors through mathematical design." He added, "It will play a vital role in fields requiring precise cellular control, such as overcoming cancer treatment resistance and developing high-efficiency smart microorganisms." Co-corresponding author Professor Jinsu Kim of POSTECH emphasized, "This research demonstrates the power of mathematical modeling, starting from theoretical formulas of intracellular noise using reaction network theory and leading to the design of actual biological mechanisms."
< Figure 3. Actual Biological Circuit Structure of the Noise Controller (NC): A representation of the mathematical model established by the research team implemented as a genetic circuit, which is an actual biological system. The existing control technology (left) consists of a reaction where the final product produces an anti-sigma factor (RsiW), which then binds with the sigma factor (SigW) that generates the system’s input value. The Noise Controller (NC) (right) similarly utilizes the binding reaction between an anti-sigma factor (RseA) and a sigma factor (ECF); however, the primary differences are that the anti-sigma factor (RseA) is produced through the dimerization reaction of the final product , and that the anti-sigma factor (RseA) directly degrades the system’s input value >
The results of this study were published on December 24 in the international academic journal Nature Communications (IF=15.7).
KAIST Unveils Cause of Performance Degradation in Electric Vehicle High-Nickel Batteries: "Added with Good Intentions
<(From left in the front row) Professor Nam-Soon Choi, Professor Dong-Hwa Seo, (back row, from left) Ph.D candidate Gihoon Lee, Ph.D candidate Seung Hee Han, Ph.D candidate Jae-Seung Kim, (top) M.S candidate Junyoung Kim>
High-nickel batteries, which are high-energy lithium-ion batteries primarily used in electric vehicles, offer high energy density but suffer from rapid performance degradation. A research team from KAIST has, for the first time globally, identified the fundamental cause of the rapid deterioration (degradation) of high-nickel batteries and proposed a new approach to solve it.
KAIST announced on December 3rd that a research team led by Professor Nam-Soon Choi of the Department of Chemical and Biomolecular Engineering, in collaboration with a research team led by Professor Dong-Hwa Seo of the Department of Materials Science and Engineering, has revealed that the electrolyte additive 'succinonitrile (CN4), which has been used to improve battery stability and lifespan, is actually the key culprit causing performance degradation in high-nickel batteries.
In a battery, electricity is generated as lithium ions travel between the cathode and the anode. A small amount of CN4 is included in the electrolyte to facilitate the movement of lithium. The research team confirmed through computer calculations that CN4, which has two nitrile (-CN) structures, attaches excessively strongly to the nickel ions on the surface of the high-nickel cathode.
The nitrile structure is a 'hook-like' structure, where carbon and nitrogen are bound by a triple bond, making it adhere well to metal ions. This strong bonding destroys the protective electrical double layer (EDL) that should form on the cathode surface. During the charging and discharging process, the cathode structure is distorted (Jahn-Teller distortion), and even electrons from the cathode are drawn out to the CN4, leading to rapid damage of the cathode.
Nickel ions that leak out during this process migrate through the electrolyte to the anode surface, where they accumulate. This nickel acts as a 'bad catalyst' that accelerates electrolyte decomposition and wastes lithium, further speeding up battery degradation.
Various analyses confirmed that CN4 transforms the high-nickel cathode surface into an abnormal layer deficient in nickel, and changes the normally stable structure into an abnormal 'rock-salt structure'.
This proves the dual nature of CN4: while useful in LCO batteries (lithium cobalt oxide), it actually causes the structural collapse in high-nickel batteries with a high nickel ratio.
This research holds significant meaning as a precise analysis that goes beyond simple control of charging/discharging conditions, to even elucidating the actual electron transfer occurring between metal ions and electrolyte molecules. Based on this achievement, the research team plans to develop a new electrolyte additive optimized for high-nickel cathodes.
<Schematic diagram of the ligand coordination between CN₄ molecules and Ni³⁺ on the high-nickel cathode surface and the cathode structural degradation process>
Professor Nam-Soon Choi stated, "A precise, molecular-level understanding is essential to enhance battery lifespan and stability. This research will pave the way for the development of new additives that do not excessively bond with nickel, significantly contributing to the commercialization of next-generation high-capacity batteries."
This research, jointly led by Professor Nam-Soon Choi, Seung Hee Han, Junyoung Kim, and Gihoon Lee of the Department of Chemical and Biomolecular Engineering, and Professor Dong-Hwa Seo and Jae-Seung Kim of the Department of Materials Science and Engineering as co-first authors, was published online on November 14th in the prestigious international journal 'ACS Energy Letters' and was selected as the cover article.
※ Paper Title: Unveiling Bidentate Nitrile-Driven Structural Degradation in Ultra-High-Nickel Cathodes,
https://doi.org/10.1021/acsenergylett.5c02845
<Cover Page of International Journal(ACS Energy Letters)>
The research was supported by Samsung SDI.
AI Opens a New Era in Medical Science and Bio
< (From left) KAIST Professors Yoonjae Choi, Tae-Kyun Kim, Jong Chul Ye, Hyunwoo Kim, Seunghoon Hong, Sang Yup Lee >
KAIST announced on the 14th of November that it has been selected as a major participating institution in the 'Lunit Consortium' for the 'AI Specialized Foundation Model Development Project' supervised by the Ministry of Science and ICT, and has officially started developing an AI foundation model for the medical science and bio fields. Through this project, KAIST plans to develop an 'AI Foundation Model Specialized for Medical Science' that encompasses the entire lifecycle of bio and medical data, and lead the creation of an AI based life science innovation ecosystem. The 'Lunit Consortium' includes 7 companies-Lunit, Trillion Labs, Kakao Healthcare, Igenscience, SK Biopharm, and Rebellion-along with 9 medical and research institutions, including KAIST, Seoul National University, NYU, National Health Insurance Service Ilsan Hospital, and Yonsei Severance Hospital. This consortium will be supported by 256 state of the art B200 GPUs to build and demonstrate a 'Chain of Evidence-Based Full-Cycle Medical Science AI Model', an AI system that connects and analyzes medical data from beginning to end, and a 'Multi-Agent Service', a system where multiple AIs collaborate to perform diagnosis and prediction. KAIST's participation in this project involves a joint research team formed by professors from the School of Computing and the Kim Jaechul Graduate School of AI. Professors Yoonjae Choi, Tae-Kyun Kim, Jong Chul Ye, Hyunwoo Kim, and Seunghoon Hong will serve as the research team, and Vice President for Research Sang Yup Lee will take on an advisory role. The research team is not merely collecting data but they are establishing a strategy (L1~L7 stages) to precisely process and systematically manage medical and life science data so that the AI can actually learn and utilize it. Through this, they plan to develop and verify an AI model that connects and analyzes diverse life science data, including medical information, gene/protein data, and new drug candidates. The data the research team aims to integrate includes a wide range from language to actual patient treatment information. Specifically, L1 represents language data, L2 is the structure of molecules, L3 is proteins and antibodies, L4 is omics data encompassing genetic and protein information, L5 is drug information, L6 is medical science research and clinical data, and L7 is real-world clinical data obtained from actual hospitals. In essence, the data handled by the AI connects everything from speech and text to molecules, proteins, drugs, clinical research, and actual patient treatment information.
< The process of training AI by viewing X ray images and doctor's interpretation (text) together (MedViLL from Professor Jae-Yoon Choi' s lab) >
Vice President Sang Yup Lee is a world-renowned scholar in the fields of synthetic biology and systems metabolic engineering, leading the establishment of a bio manufacturing platform and policy advice through the convergence of life science, engineering, and AI. He advises on the analysis of life information (omics) such as genes and proteins and designs a feedback system for verifying experimental results, supporting the Korean-developed medical AI model to secure international reliability and competitiveness. Vice President Lee stated, "AI technology is breaking down the boundaries of life science and engineering, creating a new paradigm for knowledge creation," adding, "KAIST will utilize full cycle medical science data to accelerate the era where AI uncovers the causes of diseases and predicts treatments." KAIST President Kwang Hyung Lee said, "KAIST will contribute to creating an AI-based life science innovation ecosystem, lead the innovation of national strategic industries through world-class AI-bio convergence research, and drive the progress of human health and science and technology." The model developed in the Lunit Consortium will be released as an Open License for commercial use, and is expected to expand into various medical and healthcare services such as national health chatbots. With this participation, KAIST plans to strengthen research on AI-based life science data infrastructure establishment, medical AI standardization, and AI ethics and policy advice, leading the AI transition of national bio and medical science research.
Unraveling the Secret of Cell Movement
<(From left) Professor Won Do Heo (KAIST), Postdoctoral Researcher Heeyoung Lee (KAIST, First Author), Professor Kwang-Hyun Cho (KAIST), Professor Kapsang Lee (Johns Hopkins University, USA), Dr. Sangkyu Lee (IBS), Dr. Dongsan Kim (LIBD), Dr. Yeaji Seo (Hulux) (Co-First Authors)>
Cell movement is an essential biological process, whether it's cancer cells metastasizing to other parts of the body or immune cells migrating to heal a wound. However, the principle by which cells autonomously determine their direction of movement without external stimuli has remained unknown until now.
Through this research, KAIST and an international joint research team have elucidated the principle by which cells decide their direction and move on their own, offering a crucial clue for identifying the causes of cancer metastasis and immune diseases and establishing new treatment strategies.
KAIST announced on the 10th of November that the research team led by Endowed Chair Professor Won Do Heo of the Department of Biological Sciences, in collaboration with the research team of Endowed Chair Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering, and Professor Kapsang Lee's research team at Johns Hopkins University in the US, has for the first time in the world identified the 'autonomous driving mechanism' by which cells determine their direction of movement without external signals.
The research team developed a new imaging technique called 'INSPECT (INtracellular Separation of Protein Engineered Condensation Technique)' that allows direct visualization of how proteins interact within living cells. Using this technology, they revealed the principle of the cell's internal program for autonomously deciding its direction of movement.
The team newly analyzed the operation of the key proteins that regulate cell movement, the Rho family proteins (Rac1, Cdc42, RhoA). The results showed that these proteins do not merely divide the front and back of the cell, as previously theorized, but that the cell's decision to move straight or change direction depends on which protein it binds with.
The INSPECT technology artificially implements the phenomenon of 'phase separation,' where proteins, upon binding, naturally form segregated regions that do not mix well. This technique allows for the direct visualization of how proteins actually bind within the cell using a fluorescent signal.
<Figure 1. INSPECT: A technique for visualizing Intracellular Protein-Protein Interactions">
The research team used the proteins ferritin and the fluorescent protein DsRed to make the clusters, or 'condensates,' visible to the eye when proteins bind together like small droplets.
Using this technology, the team analyzed a total of 285 pairs of interactions by combining 15 types of Rho proteins with 19 types of binding proteins, confirming actual binding in 139 pairs. Specifically, they identified that the Cdc42–FMNL protein combination is the core circuit responsible for the cell's 'straight movement,' while the Rac1–ROCK protein combination is responsible for the cell's 'change of direction.'
The research team slightly modified a part of the Rac1 protein (the 37th amino acid), which is crucial for cell direction control, to prevent it from binding well with the 'steering wheel' protein, ROCK. As a result, the cells could not change direction and continued to move in a straight line.
In contrast, in normal cells, Rac1 and ROCK bind well, forming a structure called 'arc stress fiber' at the front of the cell. This fiber enables the cell to make near-perpendicular turns when changing direction.
Furthermore, in an experiment where the environment the cells were attached to was changed, normal cells adjusted their moving speed according to the surrounding environment, but the Rac1F37W cells (cells with a broken 'steering wheel') maintained the same speed regardless of environmental changes. This demonstrates that the Rac–ROCK protein axis subtly controls the cell's ability to recognize and adapt to its surrounding environment.
<Figure 2. Analysis of the Signaling Network through Screening of Protein Interactions that Bind to a Cell Migration-Controlling Protein>
Professor Won Do Heo stated, "This research reveals that cell movement is not a random motion but is precisely controlled by an intrinsic program created by the ensemble of Rho signaling proteins and cell migration-related proteins." He added, "The newly developed INSPECT technology is a powerful tool for visualizing intracellular protein interactions and will be broadly utilized to uncover the molecular mechanisms of various life phenomena and diseases, such as cancer metastasis and neuronal cell migration."
This research, in which Dr. Heeyoung Lee of KAIST, Dr. Sangkyu Lee (currently at IBS), Dr. Yeji Seo (currently at Hulux Co., Ltd.), and Dr. Dongsan Kim (currently at LIBD) participated as co-first authors, was published in Nature Communications on October 31st.
Journal Name: A Rho GTPase-effector ensemble governs cell migration behavior
DOI: https://doi.org/10.1038/s41467-025-64635-0
The research was supported by the Samsung Future Technology Foundation and the National Research Foundation of Korea.
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).
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.