AI-Engineered "Nasal Spray Antiviral Platform" Developed to Block Flu and COVID-19
<(From Left) Professor Hyun Jung Chung, Professor Ho Min Kim, Professor Ji Eun Oh>
<(From Left) Dr. Seungju Yang, Dr. Jeongwon Yun, Ph.D candidate Jae Hyuk Kwon>
Respiratory viruses that have diverse strains and mutate rapidly, such as influenza and COVID-19, are difficult to block perfectly with vaccines alone. To solve this problem, KAIST's research team has successfully developed a nasal (intranasal) antiviral platform using AI technology to overcome the existing limitations of interferon-lambda treatments—namely, being "weak against heat and disappearing quickly from the nasal mucosa."
KAIST announced on December 15th that a joint research team—consisting of Professor Ho Min Ktim and Professor Hyun Jung Chung from the Department of Biological Sciences, and Professor Ji Eun Oh from the Graduate School of Medical Science and Engineering used AI to stably redesign the interferon-lambda protein and combined it with a delivery technology that ensures effective diffusion and long-term retention in the nasal mucosa, thereby implementing a universal prevention technology for various respiratory viruses.
Interferon-lambda is an innate immune protein produced by the body to block viral infections, playing a crucial role in stopping respiratory viruses like the common cold, flu, and COVID-19. However, when formulated as a treatment for nasal administration, its actual efficacy was limited by its vulnerability to heat, degrading enzymes, mucus, and ciliary motion.
The research team used AI protein design technology to precisely reinforce the structural weaknesses of interferon-lambda.
First, they significantly increased stability by changing the loose "loop" structures of the protein—which were prone to instability—into rigid "helix" structures that lock in place like a firm spring.
Additionally, to prevent "aggregation" (proteins sticking together to form lumps), they applied "surface engineering" to make the surface more water-compatible. They also introduced "glycoengineering," adding sugar chain (glycan) structures to the protein surface to make it even more robust and stable.
As a result, the newly produced interferon-lambda showed a massive improvement in stability, surviving for two weeks 50℃ and demonstrated the ability to diffuse rapidly even through thick nasal mucus.
The research team further protected the protein by encapsulating it in microscopic "nanoliposomes" and coated the surface with "low-molecular-weight chitosan." This significantly enhanced "mucoadhesion," allowing the treatment to stick to the nasal lining for an extended period.
When this delivery platform was applied to animal models infected with influenza, a powerful inhibitory effect was confirmed, with the virus level in the nasal cavity decreasing by more than 85%.
This technology is a mucosal immune platform that can block viral infections in their early stages simply by spraying it into the nose. It is expected to be a new therapeutic strategy that can respond quickly not only to seasonal flu but also to unexpected new or mutant viruses.
Professor Ho Min Kim stated, "Through AI-based protein design and mucosal delivery technology, we have simultaneously overcome the stability and retention time limitations of existing interferon-lambda treatments. This platform, which is stable at high temperatures and stays in the mucosa for a long time, is an innovative technology that can be used even in developing countries lacking strict cold-chain infrastructure. It also has great scalability for developing various treatments and vaccines." He added, "This is a meaningful achievement resulting from multidisciplinary convergence research, covering everything from AI protein design to drug delivery optimization and immune evaluation through infection models."
This research involved Dr. Jeongwon Yun from the KAIST InnoCORE (AI-Co-Research & Eudcation for innovative Drug Institute, AI-CRED Institute) Dr. Seungju Yang from the Department of Biological Sciences, and PhD student Jae Hyuk Kwon from the Graduate School of Medical Science and Engineering as co-first authors. The results were published consecutively in the renowned international journals Advanced Science (Nov 20) and Biomaterials Research (Nov 21).
Paper 1: Computational Design and Glycoengineering of Interferon-Lambda for Nasal Prophylaxis against Respiratory Viruses, Advanced Science, DOI: 10.1002/advs.202506764
Paper 2: Intranasal Nanoliposomes Delivering Interferon Lambda with Enhanced Mucosal Retention as an Antiviral, Biomaterials Research, DOI: 10.34133/bmr.0287
This research was conducted with support from the KAIST InnoCORE Program, Mid-Career Researcher Support Program and the Bio-Medical Technology Development Program through the National Research Foundation of Korea (NRF), Healthcare Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), the KAIST Convergence Research Institute Operation Program, and the Institute for Basic Science (IBS).
Four KAIST Scholars Named to the 2025 Highly Cited Researchers List
Four members of KAIST including Distinguished Professor Sang Yup LEE, have been selected for the '2025 Highly Cited Researchers (HCR)' list announced by Clarivate Plc, a global academic information analysis company in the United States.
HCR is a program that identifies researchers who show top 1% influence in their respective fields based on the citation frequency of papers included in Web of Science, and it is utilized as an important indicator in the evaluation of world universities and research institutions. Clarivate announced the final list this year after verifying the excellence of research performance and academic influence through rigorous qualitative and quantitative reviews.
This year, the following professors from KAIST were selected: Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering and Professor Jin-Soo Kim* from the Graduate School of Engineering Biology in the field of Biology and Biochemistry; and Professor Bumjoon Kim and Professor Jangwon Seo from the Department of Chemical and Biomolecular Engineering in the Cross-Field category.
* Professor Jin-Soo Kim is currently listed under Edgene on the HCR list, and the affiliation is scheduled to be updated to KAIST at the end of December.
< KAIST Faculty List Selected as HCR (The total number of selected researchers is 6,868, but the total number of entries by field is 7,131, as the same researchers were selected simultaneously in multiple Cross-Field categories.) >
The Cross-Field category was established to recognize researchers who have demonstrated influence across multiple fields, going beyond a single academic area. Its importance is growing with the spread of convergence research, and it is evaluated as an indicator showing that a researcher has diverse academic impact.
This year, a total of 6,868 researchers from over 1,300 institutions in 60 countries worldwide were named HCR, and a total of 76 researchers from 12 fields were selected in South Korea. While several institutions in South Korea produced HCRs, KAIST produced its HCR selectees based on globally recognized research achievements in the fields of Bioengineering, Biotechnology, and Convergence.
KAIST's 'FluidGPT' Wins Grand Prize at the 2025 AI Champion Competition
<Commemorative Photo After Winning at the 2025 AI Champions Award Ceremony>
The era has begun where an AI assistant goes beyond simple conversation to directly view the screen, make decisions, and complete tasks such as hailing a taxi or booking an SRT ticket.
KAIST (President Kwang Hyung Lee) announced on the 6th that the AutoPhone Team (Fluidez, KAIST, Korea University, Sungkyunkwan University), led by Professor Insik Shin (CEO of Fluidez Co., Ltd.) of the School of Computing, was selected as the inaugural AI Champion (1st place) in the '2025 Artificial Intelligence Champion (AI Champion) Competition,' hosted by the Ministry of Science and ICT.
This competition is the nation's largest AI technology contest, comprehensively evaluating the innovativeness, social impact, and commercial potential of AI technology. With 630 teams participating nationwide, the AutoPhone Team claimed the top honor and will receive 3 billion Korean won in research and development funding.
The technology developed by the AutoPhone Team, 'FluidGPT,' is a fully autonomous AI agent that understands a user's voice command and enables the smartphone to independently run apps, click, input, and even complete payments.
For example, when a user says, "Book an SRT ticket from Seoul Station to Busan," or "Call a taxi," FluidGPT opens the actual app and sequentially performs the necessary steps to complete the request.
The core of this technology is its 'Non-Invasive (API-Free)' structure. Previously, calling a taxi using an app required directly connecting to the app's internal system (API communication) through the taxi app's API. In contrast, this technology does not modify the existing app's code or link an API. Instead, the AI directly recognizes and operates the screen (UI), acquiring the ability to use the smartphone just like a human.
As a result, FluidGPT presents a new paradigm—"AI that sees, judges, and moves a hand on behalf of a person"—and is evaluated as a core technology that will usher in the 'AI Phone Era.'
FluidGPT moves beyond simple voice assistance to implement the concept of 'Agentic AI' (Action-Oriented Artificial Intelligence), where the AI directly views the screen, makes decisions, and takes action. As a fully action-oriented system, the AI clicks app buttons, fills in input fields, and references data to autonomously achieve the user's objective, foreshadowing an innovation in how smartphones are used.
Professor In-sik Shin of the School of Computing shared his thoughts, stating, "AI is now evolving from conversation to action. FluidGPT is a technology that understands the user's words and autonomously executes actual apps, and it will be the starting point of the 'AI Phone Era.' The AutoPhone Team possesses world-class research capabilities, and we will contribute to the widespread adoption of AI services that everyone can easily use."
KAIST President Kwang Hyung Lee remarked, "This achievement is a representative example that demonstrates KAIST's vision for AI convergence," adding, "AI technology is entering the daily lives of citizens and leading a new wave of innovation." He further added, "KAIST will continue to lead research in future core technologies such as AI and semiconductors to bolster national competitiveness."
KAIST Develops Wearable Carbon Dioxide Sensor to Enable Real-time Apnea Diagnosis
- Professor Seunghyup Yoo’s research team of the School of Electrical Engineering developed an ultralow-power carbon dioxide (CO2) sensor using a flexible and thin organic photodiode, and succeeded in real-time breathing monitoring by attaching it to a commercial mask
- Wearable devices with features such as low power, high stability, and flexibility can be utilized for early diagnosis of various diseases such as chronic obstructive pulmonary disease and sleep apnea
< Photo 1. From the left, School of Electrical Engineering, Ph.D. candidate DongHo Choi, Professor Seunghyup Yoo, and Department of Materials Science and Engineering, Bachelor’s candidate MinJae Kim >
Carbon dioxide (CO2) is a major respiratory metabolite, and continuous monitoring of CO2 concentration in exhaled breath is not only an important indicator for early detection and diagnosis of respiratory and circulatory system diseases, but can also be widely used for monitoring personal exercise status. KAIST researchers succeeded in accurately measuring CO2 concentration by attaching it to the inside of a mask.
KAIST (President Kwang-Hyung Lee) announced on February 10th that Professor Seunghyup Yoo's research team in the Department of Electrical and Electronic Engineering developed a low-power, high-speed wearable CO2 sensor capable of stable breathing monitoring in real time.
Existing non-invasive CO2 sensors had limitations in that they were large in size and consumed high power. In particular, optochemical CO2 sensors using fluorescent molecules have the advantage of being miniaturized and lightweight, but due to the photodegradation phenomenon of dye molecules, they are difficult to use stably for a long time, which limits their use as wearable healthcare sensors.
Optochemical CO2 sensors utilize the fact that the intensity of fluorescence emitted from fluorescent molecules decreases depending on the concentration of CO2, and it is important to effectively detect changes in fluorescence light.
To this end, the research team developed a low-power CO2 sensor consisting of an LED and an organic photodiode surrounding it. Based on high light collection efficiency, the sensor, which minimizes the amount of excitation light irradiated on fluorescent molecules, achieved a device power consumption of 171 μW, which is tens of times lower than existing sensors that consume several mW.
< Figure 1. Structure and operating principle of the developed optochemical carbon dioxide (CO2) sensor. Light emitted from the LED is converted into fluorescence through the fluorescent film, reflected from the light scattering layer, and incident on the organic photodiode. CO2 reacts with a small amount of water inside the fluorescent film to form carbonic acid (H2CO3), which increases the concentration of hydrogen ions (H+), and the fluorescence intensity due to 470 nm excitation light decreases. The circular organic photodiode with high light collection efficiency effectively detects changes in fluorescence intensity, lowers the power required light up the LED, and reduces light-induced deterioration. >
The research team also elucidated the photodegradation path of fluorescent molecules used in CO2 sensors, revealed the cause of the increase in error over time in photochemical sensors, and suggested an optical design method to suppress the occurrence of errors.
Based on this, the research team developed a sensor that effectively reduces errors caused by photodegradation, which was a chronic problem of existing photochemical sensors, and can be used continuously for up to 9 hours while existing technologies based on the same material can be used for less than 20 minutes, and can be used multiple times when replacing the CO2 detection fluorescent film.
< Figure 2. Wearable smart mask and real-time breathing monitoring. The fabricated sensor module consists of four elements (①: gas-permeable light-scattering layer, ②: color filter and organic photodiode, ③: light-emitting diode, ④: CO2-detecting fluorescent film). The thin and light sensor (D1: 400 nm, D2: 470 nm) is attached to the inside of the mask to monitor the wearer's breathing in real time. >
The developed sensor accurately measured CO2 concentration by being attached to the inside of a mask based on the advantages of being light (0.12 g), thin (0.7 mm), and flexible. In addition, it showed fast speed and high resolution that can monitor respiratory rate by distinguishing between inhalation and exhalation in real time.
< Photo 2. The developed sensor attached to the inside of the mask >
Professor Seunghyup Yoo said, "The developed sensor has excellent characteristics such as low power, high stability, and flexibility, so it can be widely applied to wearable devices, and can be used for the early diagnosis of various diseases such as hypercapnia, chronic obstructive pulmonary disease, and sleep apnea." He added, "In particular, it is expected to be used to improve side effects caused by rebreathing in environments where dust is generated or where masks are worn for long periods of time, such as during seasonal changes."
This study, in which KAIST's Department of Materials Science and Engineering's undergraduate student Minjae Kim and School of Electrical Engineering's doctoral student Dongho Choi participated as joint first authors, was published in the online version of Cell's sister journal, Device, on the 22nd of last month. (Paper title: Ultralow-power carbon dioxide sensor for real-time breath monitoring) DOI: https://doi.org/10.1016/j.device.2024.100681
< Photo 3. From the left, Professor Seunghyup Yoo of the School of Electrical Engineering, MinJae Kim, an undergraduate student in the Department of Materials Science and Engineering, and Dongho Choi, a doctoral student in the School of Electrical Engineering >
This study was supported by the Ministry of Trade, Industry and Energy's Materials and Components Technology Development Project, the National Research Foundation of Korea's Original Technology Development Project, and the KAIST Undergraduate Research Participation Project. This work was supported by the (URP) program.
KAIST Scientifically Identifies a Method to Prevent Dental Erosion from Carbonated Drinks
A Korean research team, which had previously visualized and scientifically proven the harmful effects of carbonated drinks like cola on dental health using nanotechnology, has now identified a mechanism for an effective method to prevent tooth damage caused by these beverages.
KAIST (represented by President Kwang Hyung Lee) announced on the 5th of December that a team led by Professor Seungbum Hong from the Department of Materials Science and Engineering, in collaboration with Seoul National University's School of Dentistry (Departments of Pediatric Dentistry and Oral Microbiology) and Professor Hye Ryung Byon’s research team from the Department of Chemistry, has revealed through nanotechnology that silver diamine fluoride (SDF)* forms a fluoride-containing protective layer on the tooth surface, effectively inhibiting cola-induced erosion.
*SDF (Silver Diamine Fluoride): A dental agent primarily used for the treatment and prevention of tooth decay. SDF strengthens carious lesions, suppresses bacterial growth, and halts the progression of cavities.
The team analyzed the surface morphology and mechanical properties of tooth enamel on a nanoscale using atomic force microscopy (AFM). They also examined the chemical properties of the nano-film formed by SDF treatment using X-ray photoelectron spectroscopy (XPS)* and Fourier-transform infrared spectroscopy (FTIR)*.
*XPS (X-ray Photoelectron Spectroscopy): A powerful surface analysis technique used to investigate the chemical composition and electronic structure of materials.
*FTIR (Fourier-Transform Infrared Spectroscopy): An analytical method that identifies the molecular structure and composition of materials by analyzing how they absorb or transmit infrared light.
The findings showed significant differences in surface roughness and elastic modulus between teeth exposed to cola with and without SDF treatment. Teeth treated with SDF exhibited minimal changes in surface roughness due to erosion (from 64 nm to 70 nm) and maintained a high elastic modulus (from 215 GPa to 205 GPa).
This was attributed to the formation of a fluoroapatite* layer by SDF, which acted as a protective shield.
*Fluoroapatite: A phosphate mineral with the chemical formula Ca₅(PO₄)₃F (calcium fluoro-phosphate). It can occur naturally or be synthesized biologically/artificially and plays a crucial role in strengthening teeth and bones.
< Figure 1. Schematic of the workflow. Surface morphology and mechanical properties of untreated and treated silver diamine fluoride (SDF) treated enamel exposed to cola were analyzed over time using atomic force microscopy (AFM). >
Professor Young J. Kim from Seoul National University's Department of Pediatric Dentistry noted, "This technology could be applied to prevent dental erosion and strengthen teeth for both children and adults. It is a cost-effective and accessible dental treatment."
< Figure 2. Changes in surface roughness and elastic modulus according to time of exposure to cola for SDF untreated and treated teeth. After 1 hour, the surface roughness of the SDF untreated teeth rapidly became rougher from 83 nm to 287 nm and the elastic modulus weakened from 125 GPa to 13 GPa, whereas the surface roughness of the SDF treated teeth changed only slightly from 64 nm to 70 nm and the elastic modulus barely changed from 215 GPa to 205 GPa, maintaining a similar state to the initial state. >
Professor Seungbum Hong emphasized, "Dental health significantly impacts quality of life. This research offers an effective non-invasive method to prevent early dental erosion, moving beyond traditional surgical treatments. By simply applying SDF, dental erosion can be prevented and enamel strengthened, potentially reducing pain and costs associated with treatment."
This study, led by the first author Aditi Saha, a PhD student in KAIST’s Department of Materials Science and Engineering, was published in the international journal Biomaterials Research on November 7 under the title "Nanoscale Study on Noninvasive Prevention of Dental Erosion of Enamel by Silver Diamine Fluoride". The research was supported by the National Research Foundation of Korea.
A KAIST Research Team Observes the Processes of Memory and Cognition in Real Time
The human brain contains approximately 86 billion neurons and 600 trillion synapses that exchange signals between the neurons to help us control the various functions of the brain including cognition, emotion, and memory. Interestingly, the number of synapses decrease with age or as a result of diseases like Alzheimer’s, and research on synapses thus attracts a lot of attention. However, limitations have existed in observing the dynamics of synapse structures in real time.
On January 9, a joint research team led by Professor Won Do Heo from the KAIST Department of Biological Sciences, Professor Hyung-Bae Kwon from Johns Hopkins School of Medicine, and Professor Sangkyu Lee from the Institute for Basic Science (IBS) revealed that they have developed the world’s first technique to allow a real-time observation of synapse formation, extinction, and alterations.
Professor Heo’s team conjugated dimerization-dependent fluorescent proteins (ddFP) to synapses in order to observe the process in which synapses create connections between neurons in real time. The team named this technique SynapShot, by combining the words ‘synapse’ and snapshot’, and successfully tracked and observed the live formation and extinction processes of synapses as well as their dynamic changes.
< Figure 1. To observe dynamically changing synapses, dimerization-dependent fluorescent protein (ddFP) was expressed to observe flourescent signals upon synapse formation as ddFP enables fluorescence detection through reversible binding to pre- and postsynaptic terminals. >
Through a joint research project, the teams led by Professor Heo and Professor Sangkyu Lee at IBS together designed a SynapShot with green and red fluorescence, and were able to easily distinguish the synapse connecting two different neurons. Additionally, by combining an optogenetic technique that can control the function of a molecule using light, the team was able to observe the changes in the synapses while simultaneously inducing certain functions of the neurons using light.
Through more joint research with the team led by Professor Hyung-Bae Kwon at the Johns Hopkins School of Medicine, Professor Heo’s team induced several situations on live mice, including visual discrimination training, exercise, and anaesthesia, and used SynapShot to observe the changes in the synapses during each situation in real time. The observations revealed that each synapse could change fairly quickly and dynamically. This was the first-ever case in which the changes in synapses were observed in a live mammal.
< Figure 2. Microscopic photos observed through changes of the flourescence of the synapse sensor (SynapShot) by cultivating the neurons of an experimental rat and expressing the SynapShot. The changes in the synapse that is created when the pre- and post-synaptic terminals come into contact and the synapse that disappears after a certain period of time are measured by the fluorescence of the SynapShot. >
Professor Heo said, “Our group developed SynapShot through a collaboration with domestic and international research teams, and have opened up the possibility for first-hand live observations of the quick and dynamic changes of synapses, which was previously difficult to do. We expect this technique to revolutionize research methodology in the neurological field, and play an important role in brightening the future of brain science.”
This research, conducted by co-first authors Seungkyu Son (Ph.D. candidate), Jinsu Lee (Ph.D. candidate) and Dr. Kanghoon Jung from Johns Hopkins, was published in the online edition of Nature Methods on January 8 under the title “Real-time visualization of structural dynamics of synapses in live cells in vivo”, and will be printed in the February volume.
< Figure 3. Simultaneous use of green-SynapShot and red-SynapShot to distinguish and observe synapses with one post-terminal and different pre-terminals. >
< Figure 4. Dimer-dependent fluorescent protein (ddFP) exists as a green fluorescent protein as well as a red fluorescent protein, and can be applied together with blue light-activated optogenetic technology. After activating Tropomyosin receptor kinase B (TrkB) by blue light using optogenetic technology, the strengthening of synaptic connections through signals of brain-derived neurotrophic factor is observed using red-SynapShot. >
< Figure 5. Micrographs showing real-time changing synapses in the visual cortex of mice trained through visual training using in vivo imaging techniques such as two-photon microscopy as well as at the cellular level. >
This research was supported by Mid-Sized Research Funds and the Singularity Project from KAIST, and by IBS.
KAIST develops an artificial muscle device that produces force 34 times its weight
- Professor IlKwon Oh’s research team in KAIST’s Department of Mechanical Engineering developed a soft fluidic switch using an ionic polymer artificial muscle that runs with ultra-low power to lift objects 34 times greater than its weight.
- Its light weight and small size make it applicable to various industrial fields such as soft electronics, smart textiles, and biomedical devices by controlling fluid flow with high precision, even in narrow spaces.
Soft robots, medical devices, and wearable devices have permeated our daily lives. KAIST researchers have developed a fluid switch using ionic polymer artificial muscles that operates at ultra-low power and produces a force 34 times greater than its weight. Fluid switches control fluid flow, causing the fluid to flow in a specific direction to invoke various movements.
KAIST (President Kwang-Hyung Lee) announced on the 4th of January that a research team under Professor IlKwon Oh from the Department of Mechanical Engineering has developed a soft fluidic switch that operates at ultra-low voltage and can be used in narrow spaces.
Artificial muscles imitate human muscles and provide flexible and natural movements compared to traditional motors, making them one of the basic elements used in soft robots, medical devices, and wearable devices. These artificial muscles create movements in response to external stimuli such as electricity, air pressure, and temperature changes, and in order to utilize artificial muscles, it is important to control these movements precisely.
Switches based on existing motors were difficult to use within limited spaces due to their rigidity and large size. In order to address these issues, the research team developed an electro-ionic soft actuator that can control fluid flow while producing large amounts of force, even in a narrow pipe, and used it as a soft fluidic switch.
< Figure 1. The separation of fluid droplets using a soft fluid switch at ultra-low voltage. >
The ionic polymer artificial muscle developed by the research team is composed of metal electrodes and ionic polymers, and it generates force and movement in response to electricity. A polysulfonated covalent organic framework (pS-COF) made by combining organic molecules on the surface of the artificial muscle electrode was used to generate an impressive amount of force relative to its weight with ultra-low power (~0.01V).
As a result, the artificial muscle, which was manufactured to be as thin as a hair with a thickness of 180 µm, produced a force more than 34 times greater than its light weight of 10 mg to initiate smooth movement. Through this, the research team was able to precisely control the direction of fluid flow with low power.
< Figure 2. The synthesis and use of pS-COF as a common electrode-electrolyte host for electroactive soft fluid switches. A) The synthesis schematic of pS-COF. B) The schematic diagram of the operating principle of the electrochemical soft switch. C) The schematic diagram of using a pS-COF-based electrochemical soft switch to control fluid flow in dynamic operation. >
Professor IlKwon Oh, who led this research, said, “The electrochemical soft fluidic switch that operate at ultra-low power can open up many possibilities in the fields of soft robots, soft electronics, and microfluidics based on fluid control.” He added, “From smart fibers to biomedical devices, this technology has the potential to be immediately put to use in a variety of industrial settings as it can be easily applied to ultra-small electronic systems in our daily lives.”
The results of this study, in which Dr. Manmatha Mahato, a research professor in the Department of Mechanical Engineering at KAIST, participated as the first author, were published in the international academic journal Science Advances on December 13, 2023. (Paper title: Polysulfonated Covalent Organic Framework as Active Electrode Host for Mobile Cation Guests in Electrochemical Soft Actuator)
This research was conducted with support from the National Research Foundation of Korea's Leader Scientist Support Project (Creative Research Group) and Future Convergence Pioneer Project.
* Paper DOI: https://www.science.org/doi/abs/10.1126/sciadv.adk9752
The cause of disability in aged brain meningeal membranes identified
Due to the increase in average age, studies on changes in the brain following general aging process without serious brain diseases have also become an issue that requires in-depth studies. Regarding aging research, as aging progresses, ‘sugar’ accumulates in the body, and the accumulated sugar becomes a causative agent for various diseases such as aging-related inflammation and vascular disease. In the end, “surplus” sugar molecules attach to various proteins in the body and interfere with their functions.
KAIST (President Kwang Hyung Lee), a joint research team of Professor Pilnam Kim and Professor Yong Jeong of the Department of Bio and Brain Engineering, revealed on the 15th that it was confirmed that the function of being the “front line of defense” for the cerebrocortex of the brain meninges, the layers of membranes that surrounds the brain, is hindered when 'sugar' begins to build up on them as aging progresses.
Professor Kim's research team confirmed excessive accumulation of sugar molecules in the meninges of the elderly and also confirmed that sugar accumulation occurs mouse models in accordance with certain age levels. The meninges are thin membranes that surround the brain and exist at the boundary between the cerebrospinal fluid and the cortex and play an important role in protecting the brain. In this study, it was revealed that the dysfunction of these brain membranes caused by aging is induced by 'excess' sugar in the brain. In particular, as the meningeal membrane becomes thinner and stickier due to aging, a new paradigm has been provided for the discovery of the principle of the decrease in material exchange between the cerebrospinal fluid and the cerebral cortex.
This research was conducted by the Ph.D. candidate Hyo Min Kim and Dr. Shinheun Kim as the co-first authors to be published online on February 28th in the international journal, Aging Cell. (Paper Title: Glycation-mediated tissue-level remodeling of brain meningeal membrane by aging)
The meninges, which are in direct contact with the cerebrospinal fluid, are mainly composed of collagen, an extracellular matrix (ECM) protein, and are composed of fibroblasts, which are cells that produce this protein. The cells that come in contact with collagen proteins that are attached with sugar have a low collagen production function, while the meningeal membrane continuously thins and collapses as the expression of collagen degrading enzymes increases.
Studies on the relationship between excess sugar molecules accumulation in the brain due to continued sugar intake and the degeneration of neurons and brain diseases have been continuously conducted. However, this study was the first to identify meningeal degeneration and dysfunction caused by glucose accumulation with the focus on the meninges itself, and the results are expected to present new ideas for research into approach towards discoveries of new treatments for brain disease.
Researcher Hyomin Kim, the first author, introduced the research results as “an interesting study that identified changes in the barriers of the brain due to aging through a convergent approach, starting from the human brain and utilizing an animal model with a biomimetic meningeal model”.
Professor Pilnam Kim's research team is conducting research and development to remove sugar that accumulated throughout the human body, including the meninges. Advanced glycation end products, which are waste products formed when proteins and sugars meet in the human body, are partially removed by macrophages. However, glycated products bound to extracellular matrix proteins such as collagen are difficult to remove naturally. Through the KAIST-Ceragem Research Center, this research team is developing a healthcare medical device to remove 'sugar residue' in the body.
This study was carried out with the National Research Foundation of Korea's collective research support.
Figure 1. Schematic diagram of proposed mechanism showing aging‐related ECM remodeling through meningeal fibroblasts on the brain leptomeninges. Meningeal fibroblasts in the young brain showed dynamic COL1A1 synthetic and COL1‐interactive function on the collagen membrane. They showed ITGB1‐mediated adhesion on the COL1‐composed leptomeningeal membrane and induction of COL1A1 synthesis for maintaining the collagen membrane. With aging, meningeal fibroblasts showed depletion of COL1A1 synthetic function and altered cell–matrix interaction.
Figure 2. Representative rat meningeal images observed in the study. Compared to young rats, it was confirmed that type 1 collagen (COL1) decreased along with the accumulation of glycated end products (AGE) in the brain membrane of aged rats, and the activity of integrin beta 1 (ITGB1), a representative receptor corresponding to cell-collagen interaction. Instead, it was observed that the activity of discoidin domain receptor 2 (DDR2), one of the tyrosine kinases, increased.
Figure 3. Substance flux through the brain membrane decreases with aging. It was confirmed that the degree of adsorption of fluorescent substances contained in cerebrospinal fluid (CSF) to the brain membrane increased and the degree of entry into the periphery of the cerebral blood vessels decreased in the aged rats. In this study, only the influx into the brain was confirmed during the entry and exit of substances, but the degree of outflow will also be confirmed through future studies.
KAIST to showcase a pack of KAIST Start-ups at CES 2023
- KAIST is to run an Exclusive Booth at the Venetian Expo (Hall G) in Eureka Park, at CES 2023, to be held in Las Vegas from Thursday, January 5th through Sunday, the 8th.
- Twelve businesses recently put together by KAIST faculty, alumni, and the start-ups given legal usage of KAIST technologies will be showcased.
- Out of the participating start-ups, the products by Fluiz and Hills Robotics were selected as the “CES Innovation Award 2023 Honoree”, scoring top in their respective categories.
On January 3, KAIST announced that there will be a KAIST booth at Consumer Electronics Show (CES) 2023, the most influential tech event in the world, to be held in Las Vegas from January 3 to 8.
At this exclusive corner, KAIST will introduce the technologies of KAIST start-ups over the exhibition period.
KAIST first started holding its exclusive booth in CES 2019 with five start-up businesses, following up at CES 2020 with 12 start-ups and at CES 2022 with 10 start-ups. At CES 2023, which would be KAIST’s fourth conference, KAIST will be accompanying 12 businesses including start-ups by the faculty members, alumni, and technology transfer companies that just began their businesses with technologies from their research findings that stands a head above others.
To maximize the publicity opportunity, KAIST will support each company’s marketing strategies through cooperation with the Korea International Trade Association (KITA), and provide an opportunity for the school and each startup to create global identity and exhibit the excellence of their technologies at the convention.
The following companies will be at the KAIST Booth in Eureka Park:
The twelve startups mentioned above aim to achieve global technology commecialization in their respective fields of expertise spanning from eXtended Reality (XR) and gaming, to AI and robotics, vehicle and transport, mobile platform, smart city, autonomous driving, healthcare, internet of thing (IoT), through joint research and development, technology transfer and investment attraction from world’s leading institutions and enterprises.
In particular, Fluiz and Hills Robotics won the CES Innovation Award as 2023 Honorees and is expected to attain greater achievements in the future.
A staff member from the KAIST Institute of Technology Value Creation said, “The KAIST Showcase for CES 2023 has prepared a new pitching space for each of the companies for their own IR efforts, and we hope that KAIST startups will actively and effectively market their products and technologies while they are at the convention. We hope it will help them utilize their time here to establish their name in presence here which will eventually serve as a good foothold for them and their predecessors to further global commercialization goals.”
PICASSO Technique Drives Biological Molecules into Technicolor
The new imaging approach brings current imaging colors from four to more than 15 for mapping overlapping proteins
Pablo Picasso’s surreal cubist artistic style shifted common features into unrecognizable scenes, but a new imaging approach bearing his namesake may elucidate the most complicated subject: the brain. Employing artificial intelligence to clarify spectral color blending of tiny molecules used to stain specific proteins and other items of research interest, the PICASSO technique, allows researchers to use more than 15 colors to image and parse our overlapping proteins.
The PICASSO developers, based in Korea, published their approach on May 5 in Nature Communications.
Fluorophores — the staining molecules — emit specific colors when excited by a light, but if more than four fluorophores are used, their emitted colors overlap and blend. Researchers previously developed techniques to correct this spectral overlap by precisely defining the matrix of mixed and unmixed images. This measurement depends on reference spectra, found by identifying clear images of only one fluorophore-stained specimen or of multiple, identically prepared specimens that only contain a single fluorophore each.
“Such reference spectra measurement could be complicated to perform in highly heterogeneous specimens, such as the brain, due to the highly varied emission spectra of fluorophores depending on the subregions from which the spectra were measured,” said co-corresponding author Young-Gyu Yoon, professor in the School of Electrical Engineering at KAIST. He explained that the subregions would each need their own spectra reference measurements, making for an inefficient, time-consuming process. “To address this problem, we developed an approach that does not require reference spectra measurements.”
The approach is the “Process of ultra-multiplexed Imaging of biomolecules viA the unmixing of the Signals of Spectrally Overlapping fluorophores,” also known as PICASSO. Ultra-multiplexed imaging refers to visualizing the numerous individual components of a unit. Like a cinema multiplex in which each theater plays a different movie, each protein in a cell has a different role. By staining with fluorophores, researchers can begin to understand those roles.
“We devised a strategy based on information theory; unmixing is performed by iteratively minimizing the mutual information between mixed images,” said co-corresponding author Jae-Byum Chang, professor in the Department of Materials Science and Engineering, KAIST. “This allows us to get away with the assumption that the spatial distribution of different proteins is mutually exclusive and enables accurate information unmixing.”
To demonstrate PICASSO’s capabilities, the researchers applied the technique to imaging a mouse brain. With a single round of staining, they performed 15-color multiplexed imaging of a mouse brain. Although small, mouse brains are still complex, multifaceted organs that can take significant resources to map. According to the researchers, PICASSO can improve the capabilities of other imaging techniques and allow for the use of even more fluorophore colors.
Using one such imaging technique in combination with PICASSO, the team achieved 45-color multiplexed imaging of the mouse brain in only three staining and imaging cycles, according to Yoon.
“PICASSO is a versatile tool for the multiplexed biomolecule imaging of cultured cells, tissue slices and clinical specimens,” Chang said. “We anticipate that PICASSO will be useful for a broad range of applications for which biomolecules’ spatial information is important. One such application the tool would be useful for is revealing the cellular heterogeneities of tumor microenvironments, especially the heterogeneous populations of immune cells, which are closely related to cancer prognoses and the efficacy of cancer therapies.”
The Samsung Research Funding & Incubation Center for Future Technology supported this work. Spectral imaging was performed at the Korea Basic Science Institute Western Seoul Center.
-PublicationJunyoung Seo, Yeonbo Sim, Jeewon Kim, Hyunwoo Kim, In Cho, Hoyeon Nam, Yong-Gyu Yoon, Jae-Byum Chang, “PICASSO allows ultra-multiplexed fluorescence imaging of spatiallyoverlapping proteins without reference spectra measurements,” May 5, Nature Communications (doi.org/10.1038/s41467-022-30168-z)
-ProfileProfessor Jae-Byum ChangDepartment of Materials Science and EngineeringCollege of EngineeringKAIST
Professor Young-Gyu YoonSchool of Electrical EngineeringCollege of EngineeringKAIST
Label-Free Multiplexed Microtomography of Endogenous Subcellular Dynamics Using Deep Learning
AI-based holographic microscopy allows molecular imaging without introducing exogenous labeling agents
A research team upgraded the 3D microtomography observing dynamics of label-free live cells in multiplexed fluorescence imaging. The AI-powered 3D holotomographic microscopy extracts various molecular information from live unlabeled biological cells in real time without exogenous labeling or staining agents.
Professor YongKeum Park’s team and the startup Tomocube encoded 3D refractive index tomograms using the refractive index as a means of measurement. Then they decoded the information with a deep learning-based model that infers multiple 3D fluorescence tomograms from the refractive index measurements of the corresponding subcellular targets, thereby achieving multiplexed micro tomography. This study was reported in Nature Cell Biology online on December 7, 2021.
Fluorescence microscopy is the most widely used optical microscopy technique due to its high biochemical specificity. However, it needs to genetically manipulate or to stain cells with fluorescent labels in order to express fluorescent proteins. These labeling processes inevitably affect the intrinsic physiology of cells. It also has challenges in long-term measuring due to photobleaching and phototoxicity. The overlapped spectra of multiplexed fluorescence signals also hinder the viewing of various structures at the same time. More critically, it took several hours to observe the cells after preparing them.
3D holographic microscopy, also known as holotomography, is providing new ways to quantitatively image live cells without pretreatments such as staining. Holotomography can accurately and quickly measure the morphological and structural information of cells, but only provides limited biochemical and molecular information.
The 'AI microscope' created in this process takes advantage of the features of both holographic microscopy and fluorescence microscopy. That is, a specific image from a fluorescence microscope can be obtained without a fluorescent label. Therefore, the microscope can observe many types of cellular structures in their natural state in 3D and at the same time as fast as one millisecond, and long-term measurements over several days are also possible.
The Tomocube-KAIST team showed that fluorescence images can be directly and precisely predicted from holotomographic images in various cells and conditions. Using the quantitative relationship between the spatial distribution of the refractive index found by AI and the major structures in cells, it was possible to decipher the spatial distribution of the refractive index. And surprisingly, it confirmed that this relationship is constant regardless of cell type.
Professor Park said, “We were able to develop a new concept microscope that combines the advantages of several microscopes with the multidisciplinary research of AI, optics, and biology. It will be immediately applicable for new types of cells not included in the existing data and is expected to be widely applicable for various biological and medical research.”
When comparing the molecular image information extracted by AI with the molecular image information physically obtained by fluorescence staining in 3D space, it showed a 97% or more conformity, which is a level that is difficult to distinguish with the naked eye.
“Compared to the sub-60% accuracy of the fluorescence information extracted from the model developed by the Google AI team, it showed significantly higher performance,” Professor Park added.
This work was supported by the KAIST Up program, the BK21+ program, Tomocube, the National Research Foundation of Korea, and the Ministry of Science and ICT, and the Ministry of Health & Welfare.
-Publication
Hyun-seok Min, Won-Do Heo, YongKeun Park, et al. “Label-free multiplexed microtomography of endogenous subcellular dynamics using generalizable deep learning,” Nature Cell Biology (doi.org/10.1038/s41556-021-00802-x) published online December 07 2021.
-Profile
Professor YongKeun Park
Biomedical Optics Laboratory
Department of Physics
KAIST
A Study Shows Reactive Electrolyte Additives Improve Lithium Metal Battery Performance
Stable electrode-electrolyte interfaces constructed by fluorine- and nitrogen-donating ionic additives provide an opportunity to improve high-performance lithium metal batteries
A research team showed that electrolyte additives increase the lifetime of lithium metal batteries and remarkably improve the performance of fast charging and discharging. Professor Nam-Soon Choi’s team from the Department of Chemical and Biomolecular Engineering at KAIST hierarchized the solid electrolyte interphase to make a dual-layer structure and showed groundbreaking run times for lithium metal batteries.
The team applied two electrolyte additives that have different reduction and adsorption properties to improve the functionality of the dual-layer solid electrolyte interphase. In addition, the team has confirmed that the structural stability of the nickel-rich cathode was achieved through the formation of a thin protective layer on the cathode. This study was reported in Energy Storage Materials.
Securing high-energy-density lithium metal batteries with a long lifespan and fast charging performance is vital for realizing their ubiquitous use as superior power sources for electric vehicles. Lithium metal batteries comprise a lithium metal anode that delivers 10 times higher capacity than the graphite anodes in lithium-ion batteries. Therefore, lithium metal is an indispensable anode material for realizing high-energy rechargeable batteries. However, undesirable reactions among the electrolytes with lithium metal anodes can reduce the power and this remains an impediment to achieving a longer battery lifespan. Previous studies only focused on the formation of the solid electrolyte interphase on the surface of the lithium metal anode.
The team designed a way to create a dual-layer solid electrolyte interphase to resolve the instability of the lithium metal anode by using electrolyte additives, depending on their electron accepting ability and adsorption tendencies. This hierarchical structure of the solid electrolyte interphase on the lithium metal anode has the potential to be further applied to lithium-alloy anodes, lithium storage structures, and anode-free technology to meet market expectations for electrolyte technology.
The batteries with lithium metal anodes and nickel-rich cathodes represented 80.9% of the initial capacity after 600 cycles and achieved a high Coulombic efficiency of 99.94%. These remarkable results contributed to the development of protective dual-layer solid electrolyte interphase technology for lithium metal anodes.
Professor Choi said that the research suggests a new direction for the development of electrolyte additives to regulate the unstable lithium metal anode-electrolyte interface, the biggest hurdle in research on lithium metal batteries.
She added that anode-free secondary battery technology is expected to be a game changer in the secondary battery market and electrolyte additive technology will contribute to the enhancement of anode-free secondary batteries through the stabilization of lithium metal anodes.
This research was funded by the Technology Development Program to Solve Climate Change of the National Research Foundation in Korea funded by the Ministry of Science, ICT & Future Planning and the Technology Innovation Program funded by the Ministry of Trade, Industry & Energy, and Hyundai Motor Company.
- PublicationSaehun Kim, Sung O Park, Min-Young Lee, Jeong-A Lee, Imanuel Kristanto, Tae Kyung Lee, Daeyeon Hwang, Juyoung Kim, Tae-Ung Wi, Hyun-Wook Lee, Sang Kyu Kwak, and NamSoon Choi, “Stable electrode-electrolyte interfaces constructed by fluorine- and nitrogen-donating ionic additives for high-performance lithium metal batteries,” Energy Storage Materials,45, 1-13 (2022), (doi: https://doi.org/10.1016/j.ensm.2021.10.031)
- ProfileProfessor Nam-Soon ChoiEnergy Materials LaboratoryDepartment of Chemical and Biomolecular EngineeringKAIST