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KAIST-UCSD researchers build an enzyme discovering AI
- A joint research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering and Bernhard Palsson of UCSD developed ‘DeepECtransformer’, an artificial intelligence that can predict Enzyme Commission (EC) number of proteins.
- The AI is tasked to discover new enzymes that have not been discovered yet, which would allow prediction for a total of 5,360 types of Enzyme Commission (EC) numbers
- It is expected to be used in the development of microbial cell factories that produce environmentally friendly chemicals as a core technology for analyzing the metabolic network of a genome.
While E. coli is one of the most studied organisms, the function of 30% of proteins that make up E. coli has not yet been clearly revealed. For this, an artificial intelligence was used to discover 464 types of enzymes from the proteins that were unknown, and the researchers went on to verify the predictions of 3 types of proteins were successfully identified through in vitro enzyme assay.
KAIST (President Kwang-Hyung Lee) announced on the 24th that a joint research team comprised of Gi Bae Kim, Ji Yeon Kim, Dr. Jong An Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, and Dr. Charles J. Norsigian and Professor Bernhard O. Palsson of the Department of Bioengineering at UCSD has developed DeepECtransformer, an artificial intelligence that can predict the enzyme functions from the protein sequence, and has established a prediction system by utilizing the AI to quickly and accurately identify the enzyme function.
Enzymes are proteins that catalyze biological reactions, and identifying the function of each enzyme is essential to understanding the various chemical reactions that exist in living organisms and the metabolic characteristics of those organisms. Enzyme Commission (EC) number is an enzyme function classification system designed by the International Union of Biochemistry and Molecular Biology, and in order to understand the metabolic characteristics of various organisms, it is necessary to develop a technology that can quickly analyze enzymes and EC numbers of the enzymes present in the genome.
Various methodologies based on deep learning have been developed to analyze the features of biological sequences, including protein function prediction, but most of them have a problem of a black box, where the inference process of AI cannot be interpreted. Various prediction systems that utilize AI for enzyme function prediction have also been reported, but they do not solve this black box problem, or cannot interpret the reasoning process in fine-grained level (e.g., the level of amino acid residues in the enzyme sequence).
The joint team developed DeepECtransformer, an AI that utilizes deep learning and a protein homology analysis module to predict the enzyme function of a given protein sequence. To better understand the features of protein sequences, the transformer architecture, which is commonly used in natural language processing, was additionally used to extract important features about enzyme functions in the context of the entire protein sequence, which enabled the team to accurately predict the EC number of the enzyme. The developed DeepECtransformer can predict a total of 5360 EC numbers.
The joint team further analyzed the transformer architecture to understand the inference process of DeepECtransformer, and found that in the inference process, the AI utilizes information on catalytic active sites and/or the cofactor binding sites which are important for enzyme function. By analyzing the black box of DeepECtransformer, it was confirmed that the AI was able to identify the features that are important for enzyme function on its own during the learning process.
"By utilizing the prediction system we developed, we were able to predict the functions of enzymes that had not yet been identified and verify them experimentally," said Gi Bae Kim, the first author of the paper. "By using DeepECtransformer to identify previously unknown enzymes in living organisms, we will be able to more accurately analyze various facets involved in the metabolic processes of organisms, such as the enzymes needed to biosynthesize various useful compounds or the enzymes needed to biodegrade plastics." he added.
"DeepECtransformer, which quickly and accurately predicts enzyme functions, is a key technology in functional genomics, enabling us to analyze the function of entire enzymes at the systems level," said Professor Sang Yup Lee. He added, “We will be able to use it to develop eco-friendly microbial factories based on comprehensive genome-scale metabolic models, potentially minimizing missing information of metabolism.”
The joint team’s work on DeepECtransformer is described in the paper titled "Functional annotation of enzyme-encoding genes using deep learning with transformer layers" written by Gi Bae Kim, Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering of KAIST and their colleagues. The paper was published via peer-review on the 14th of November on “Nature Communications”.
This research was conducted with the support by “the Development of next-generation biorefinery platform technologies for leading bio-based chemicals industry project (2022M3J5A1056072)” and by “Development of platform technologies of microbial cell factories for the next-generation biorefineries project (2022M3J5A1056117)” from National Research Foundation supported by the Korean Ministry of Science and ICT (Project Leader: Distinguished Professor Sang Yup Lee, KAIST).
< Figure 1. The structure of DeepECtransformer's artificial neural network >
2023.11.24 View 5001 -
An intravenous needle that irreversibly softens via body temperature on insertion
- A joint research team at KAIST developed an intravenous (IV) needle that softens upon insertion, minimizing risk of damage to blood vessels and tissues.
- Once used, it remains soft even at room temperature, preventing accidental needle stick injuries and unethical multiple use of needle.
- A thin-film temperature sensor can be embedded with this needle, enabling real-time monitoring of the patient's core body temperature, or detection of unintended fluid leakage, during IV medication.
Intravenous (IV) injection is a method commonly used in patient’s treatment worldwide as it induces rapid effects and allows treatment through continuous administration of medication by directly injecting drugs into the blood vessel. However, medical IV needles, made of hard materials such as stainless steel or plastic which do not mechanically match the soft biological tissues of the body, can cause critical problems in healthcare settings, starting from minor tissue damages in the injection sites to serious inflammations.
The structure and dexterity of rigid medical IV devices also enable unethical reuse of needles for reduction of injection costs, leading to transmission of deadly blood-borne disease infections such as human immunodeficiency virus (HIV) and hepatitis B/C viruses. Furthermore, unintended needlestick injuries are frequently occurring in medical settings worldwide, that are viable sources of such infections, with IV needles having the greatest susceptibility of being the medium of transmissible diseases. For these reasons, the World Health Organization (WHO) in 2015 launched a policy on safe injection practices to encourage the development and use of “smart” syringes that have features to prevent re-use, after a tremendous increase in the number of deadly infectious disease worldwide due to medical-sharps related issues.
KAIST announced on the 13th that Professor Jae-Woong Jeong and his research team of its School of Electrical Engineering succeeded in developing the Phase-Convertible, Adapting and non-REusable (P-CARE) needle with variable stiffness that can improve patient health and ensure the safety of medical staff through convergent joint research with another team led by Professor Won-Il Jeong of the Graduate School of Medical Sciences.
The new technology is expected to allow patients to move without worrying about pain at the injection site as it reduces the risk of damage to the wall of the blood vessel as patients receive IV medication. This is possible with the needle’s stiffness-tunable characteristics which will make it soft and flexible upon insertion into the body due to increased temperature, adapting to the movement of thin-walled vein. It is also expected to prevent blood-borne disease infections caused by accidental needlestick injuries or unethical re-using of syringes as the deformed needle remains perpetually soft even after it is retracted from the injection site.
The results of this research, in which Karen-Christian Agno, a doctoral researcher of the School of Electrical Engineering at and Dr. Keungmo Yang of the Graduate School of Medical Sciences participated as co-first authors, was published in Nature Biomedical Engineering on October 30. (Paper title: A temperature-responsive intravenous needle that irreversibly softens on insertion)
< Figure 1. Disposable variable stiffness intravenous needle. (a) Conceptual illustration of the key features of the P-CARE needle whose mechanical properties can be changed by body temperature, (b) Photograph of commonly used IV access devices and the P-CARE needle, (c) Performance of common IV access devices and the P-CARE needle >
“We’ve developed this special needle using advanced materials and micro/nano engineering techniques, and it can solve many global problems related to conventional medical needles used in healthcare worldwide”, said Jae-Woong Jeong, Ph.D., an associate professor of Electrical Engineering at KAIST and a lead senior author of the study.
The softening IV needle created by the research team is made up of liquid metal gallium that forms the hollow, mechanical needle frame encapsulated within an ultra-soft silicone material. In its solid state, gallium has sufficient hardness that enables puncturing of soft biological tissues. However, gallium melts when it is exposed to body temperature upon insertion, and changes it into a soft state like the surrounding tissue, enabling stable delivery of the drug without damaging blood vessels. Once used, a needle remains soft even at room temperature due to the supercooling phenomenon of gallium, fundamentally preventing needlestick accidents and reuse problems.
Biocompatibility of the softening IV needle was validated through in vivo studies in mice. The studies showed that implanted needles caused significantly less inflammation relative to the standard IV access devices of similar size made of metal needles or plastic catheters. The study also confirmed the new needle was able to deliver medications as reliably as commercial injection needles.
< Photo 1. Photo of the P-CARE needle that softens with body temperature. >
Researchers also showed possibility of integrating a customized ultra-thin temperature sensor with the softening IV needle to measure the on-site temperature which can further enhance patient’s well-being. The single assembly of sensor-needle device can be used to monitor the core body temperature, or even detect if there is a fluid leakage on-site during indwelling use, eliminating the need for additional medical tools or procedures to provide the patients with better health care services.
The researchers believe that this transformative IV needle can open new opportunities for wide range of applications particularly in clinical setups, in terms of redesigning other medical needles and sharp medical tools to reduce muscle tissue injury during indwelling use. The softening IV needle may become even more valuable in the present times as there is an estimated 16 billion medical injections administered annually in a global scale, yet not all needles are disposed of properly, based on a 2018 WHO report.
< Figure 2. Biocompatibility test for P-CARE needle: Images of H&E stained histology (the area inside the dashed box on the left is provided in an expanded view in the right), TUNEL staining (green), DAPI staining of nuclei (blue) and co-staining (TUNEL and DAPI) of muscle tissue from different organs. >
< Figure 3. Conceptual images of potential utilization for temperature monitoring function of P-CARE needle integrated with a temperature sensor. >
(a) Schematic diagram of injecting a drug through intravenous injection into the abdomen of a laboratory mouse (b) Change of body temperature upon injection of drug (c) Conceptual illustration of normal intravenous drug injection (top) and fluid leakage (bottom) (d) Comparison of body temperature during normal drug injection and fluid leakage: when the fluid leak occur due to incorrect insertion, a sudden drop of temperature is detected.
This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT.
2023.11.13 View 8057 -
KAIST proposes alternatives to chemical factories through “iBridge”
- A computer simulation program “iBridge” was developed at KAIST that can put together microbial cell factories quickly and efficiently to produce cosmetics and food additives, and raw materials for nylons
- Eco-friendly and sustainable fermentation process to establish an alternative to chemical plants
As climate change and environmental concerns intensify, sustainable microbial cell factories garner significant attention as candidates to replace chemical plants. To develop microorganisms to be used in the microbial cell factories, it is crucial to modify their metabolic processes to induce efficient target chemical production by modulating its gene expressions. Yet, the challenge persists in determining which gene expressions to amplify and suppress, and the experimental verification of these modification targets is a time- and resource-intensive process even for experts. The challenges were addressed by a team of researchers at KAIST (President Kwang-Hyung Lee) led by Distinguished Professor Sang Yup Lee.
It was announced on the 9th by the school that a method for building a microbial factory at low cost, quickly and efficiently, was presented by a novel computer simulation program developed by the team under Professor Lee’s guidance, which is named “iBridge”. This innovative system is designed to predict gene targets to either overexpress or downregulate in the goal of producing a desired compound to enable the cost-effective and efficient construction of microbial cell factories specifically tailored for producing the chemical compound in demand from renewable biomass.
Systems metabolic engineering is a field of research and engineering pioneered by KAIST’s Distinguished Professor Sang Yup Lee that seeks to produce valuable compounds in industrial demands using microorganisms that are re-configured by a combination of methods including, but not limited to, metabolic engineering, synthetic biology, systems biology, and fermentation engineering.
In order to improve microorganisms’ capability to produce useful compounds, it is essential to delete, suppress, or overexpress microbial genes. However, it is difficult even for the experts to identify the gene targets to modify without experimental confirmations for each of them, which can take up immeasurable amount of time and resources.
The newly developed iBridge identifies positive and negative metabolites within cells, which exert positive and/or negative impact on formation of the products, by calculating the sum of covariances of their outgoing (consuming) reaction fluxes for a target chemical. Subsequently, it pinpoints "bridge" reactions responsible for converting negative metabolites into positive ones as candidates for overexpression, while identifying the opposites as targets for downregulation.
The research team successfully utilized the iBridge simulation to establish E. coli microbial cell factories each capable of producing three of the compounds that are in high demands at a production capacity that has not been reported around the world. They developed E. coli strains that can each produce panthenol, a moisturizing agent found in many cosmetics, putrescine, which is one of the key components in nylon production, and 4-hydroxyphenyllactic acid, an anti-bacterial food additive. In addition to these three compounds, the study presents predictions for overexpression and suppression genes to construct microbial factories for 298 other industrially valuable compounds.
Dr. Youngjoon Lee, the co-first author of this paper from KAIST, emphasized the accelerated construction of various microbial factories the newly developed simulation enabled. He stated, "With the use of this simulation, multiple microbial cell factories have been established significantly faster than it would have been using the conventional methods. Microbial cell factories producing a wider range of valuable compounds can now be constructed quickly using this technology."
Professor Sang Yup Lee said, "Systems metabolic engineering is a crucial technology for addressing the current climate change issues." He added, "This simulation could significantly expedite the transition from resorting to conventional chemical factories to utilizing environmentally friendly microbial factories."
< Figure. Conceptual diagram of the flow of iBridge simulation >
The team’s work on iBridge is described in a paper titled "Genome-Wide Identification of Overexpression and Downregulation Gene Targets Based on the Sum of Covariances of the Outgoing Reaction Fluxes" written by Dr. Won Jun Kim, and Dr. Youngjoon Lee of the Bioprocess Research Center and Professors Hyun Uk Kim and Sang Yup Lee of the Department of Chemical and Biomolecular Engineering of KAIST. The paper was published via peer-review on the 6th of November on “Cell Systems” by Cell Press.
This research was conducted with the support from the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project (Project Leader: Distinguished Professor Sang Yup Lee, KAIST) and Development of Platform Technology for the Production of Novel Aromatic Bioplastic using Microbial Cell Factories Project (Project Leader: Research Professor So Young Choi, KAIST) of the Korean Ministry of Science and ICT.
2023.11.09 View 6881 -
NYU-KAIST Global AI & Digital Governance Conference Held
< Photo 1. Opening of NYU-KAIST Global AI & Digital Governance Conference >
In attendance of the Minister of Science and ICT Jong-ho Lee, NYU President Linda G. Mills, and KAIST President Kwang Hyung Lee, KAIST co-hosted the NYU-KAIST Global AI & Digital Governance Conference at the Paulson Center of New York University (NYU) in New York City, USA on September 21st, 9:30 pm.
At the conference, KAIST and NYU discussed the direction and policies for ‘global AI and digital governance’ with participants of upto 300 people which includes scholars, professors, and students involved in the academic field of AI and digitalization from both Korea and the United States and other international backgrounds. This conference was a forum of an international discussion that sought new directions for AI and digital technology take in the future and gathered consensus on regulations.
Following a welcoming address by KAIST President, Kwang Hyung Lee and a congratulatory message from the Minister of Science and ICT, Jong-ho Lee, a panel discussion was held, moderated by Professor Matthew Liao, a graduate of Princeton and Oxford University, currently serving as a professor at NYU and the director at the Center for Bioethics of the NYU School of Global Public Health.
Six prominent scholars took part in the panel discussion. Prof. Kyung-hyun Cho of NYU Applied Mathematics and Data Science Center, a KAIST graduate who has joined the ranks of the world-class in AI language models and Professor Jong Chul Ye, the Director of Promotion Council for Digital Health at KAIST, who is leading innovative research in the field of medical AI working in collaboration with major hospitals at home and abroad was on the panel. Additionally, Professor Luciano Floridi, a founding member of the Yale University Center for Digital Ethics, Professor Shannon Vallor, the Baillie Gifford Professor in the Ethics of Data and Artificial Intelligence at the University of Edinburgh of the UK, Professor Stefaan Verhulst, a Co-Founder and the DIrector of GovLab‘s Data Program at NYU’s Tandon School of Engineering, and Professor Urs Gasser, who is in charge of public policy, governance and innovative technology at the Technical University of Munich, also participated.
Professor Matthew Liao from NYU led the discussion on various topics such as the ways to to regulate AI and digital technologies; the concerns about how deep learning technology being developed in medicinal purposes could be used in warfare; the scope of responsibilities Al scientists' responsibility should carry in ensuring the usage of AI are limited to benign purposes only; the effects of external regulation on the AI model developers and the research they pursue; and on the lessons that can be learned from the regulations in other fields.
During the panel discussion, there was an exchange of ideas about a system of standards that could harmonize digital development and regulatory and social ethics in today’s situation in which digital transformation accelerates technological development at a global level, there is a looming concern that while such advancements are bringing economic vitality it may create digital divides and probles like manipulation of public opinion. Professor Jong-cheol Ye of KAIST (Director of the Promotion Council for Digital Health), in particular, emphasized that it is important to find a point of balance that does not hinder the advancements rather than opting to enforcing strict regulations.
< Photo 2. Panel Discussion in Session at NYU-KAIST Global AI & Digital Governance Conference >
KAIST President Kwang Hyung Lee explained, “At the Digital Governance Forum we had last October, we focused on exploring new governance to solve digital challenges in the time of global digital transition, and this year’s main focus was on regulations.”
“This conference served as an opportunity of immense value as we came to understand that appropriate regulations can be a motivation to spur further developments rather than a hurdle when it comes to technological advancements, and that it is important for us to clearly understand artificial intelligence and consider what should and can be regulated when we are to set regulations on artificial intelligence,” he continued.
Earlier, KAIST signed a cooperation agreement with NYU to build a joint campus, June last year and held a plaque presentation ceremony for the KAIST NYU Joint Campus last September to promote joint research between the two universities. KAIST is currently conducting joint research with NYU in nine fields, including AI and digital research. The KAIST-NYU Joint Campus was conceived with the goal of building an innovative sandbox campus centering aroung science, technology, engineering, and mathematics (STEM) combining NYU's excellent humanities and arts as well as basic science and convergence research capabilities with KAIST's science and technology.
KAIST has contributed to the development of Korea's industry and economy through technological innovation aiding in the nation’s transformation into an innovative nation with scientific and technological prowess. KAIST will now pursue an anchor/base strategy to raise KAIST's awareness in New York through the NYU Joint Campus by establishing a KAIST campus within the campus of NYU, the heart of New York.
2023.09.22 View 8991 -
KAIST holds its first ‘KAIST Tech Fair’ in New York, USA
< Photo 1. 2023 KAIST Tech Fair in New York >
KAIST (President Kwang-Hyung Lee) announced on the 11th that it will hold the ‘2023 KAIST Tech Fair in New York’ at the Kimmel Center at New York University in Manhattan, USA, on the 22nd of this month. It is an event designed to be the starting point for KAIST to expand its startup ecosystem into the global stage, and it is to attract investments and secure global customers in New York by demonstrating the technological value of KAIST startup companies directly at location.
< Photo 2. President Kwang Hyung Lee at the 2023 KAIST Tech Fair in New York >
KAIST has been holding briefing sessions for technology transfer in Korea every year since 2018, and this year is the first time to hold a tech fair overseas for global companies.
KAIST Institute of Technology Value Creation (Director Sung-Yool Choi) has prepared for this event over the past six months with the Korea International Trade Association (hereinafter KITA, CEO Christopher Koo) to survey customer base and investment companies to conduct market analysis.
Among the companies founded with the technologies developed by the faculty and students of KAIST and their partners, 7 companies were selected to be matched with companies overseas that expressed interests in these technologies. Global multinational companies in the fields of IT, artificial intelligence, environment, logistics, distribution, and retail are participating as demand agencies and are testing the marketability of the start-up's technology as of September.
Daim Research, founded by Professor Young Jae Jang of the Department of Industrial and Systems Engineering, is a company specializing in smart factory automation solutions and is knocking on the door of the global market with a platform technology optimized for automated logistics systems.
< Photo 3. Presentation by Professor Young Jae Jang for DAIM Research >
It is a ‘collaborative intelligence’ solution that maximizes work productivity by having a number of robots used in industrial settings collaborate with one another. The strength of their solution is that logistics robots equipped with AI reinforced learning technology can respond to processes and environmental changes on their own, minimizing maintenance costs and the system can achieve excellent performance even with a small amount of data when it is combined with the digital twin technology the company has developed on its own.
A student startup, ‘Aniai’, is entering the US market, the home of hamburgers, with hamburger patty automation equipments and solutions. This is a robot kitchen startup founded by its CEO Gunpil Hwang, a graduate of KAIST’s School of Electrical Engineering which gathered together the experts in the fields of robot control, design, and artificial intelligence and cognitive technology to develop technology to automatically cook hamburger patties.
At the touch of a button, both sides of the patty are cooked simultaneously for consistent taste and quality according to the set condition. Since it can cook about 200 dishes in an hour, it is attracting attention as a technology that can not only solve manpower shortages but also accelerate the digital transformation of the restaurant industry.
Also, at the tech fair to be held at the Kimmel Center of New York University on the 22nd, the following startups who are currently under market verification in the U.S. will be participating: ▴'TheWaveTalk', which developed a water quality management system that can measure external substances and metal ions by transferring original technology from KAIST; ▴‘VIRNECT’, which helps workers improve their skills by remotely managing industrial sites using XR*; ▴‘Datumo’, a solution that helps process and analyze artificial intelligence big data, ▴‘VESSL AI’, the provider of a solution to eliminate the overhead** of machine learning systems; and ▴ ‘DolbomDream’, which developed an inflatable vest that helps the psychological stability of people with developmental disabilities.
* XR (eXtended Reality): Ultra-realistic technology that enhances immersion by utilizing augmented reality, virtual reality, and mixed reality technologies
** Overhead: Additional time required for stable processing of the program
In addition, two companies (Plasmapp and NotaAI) that are participating in the D-Unicorn program with the support of the Daejeon City and two companies (Enget and ILIAS Biologics) that are receiving support from the Scale Up Tips of the Ministry of SMEs and Startups, three companies (WiPowerOne, IDK Lab, and Artificial Photosynthesis Lab) that are continuing to realize the sustainable development goals for a total of 14 KAIST startups, will hold a corporate information session with about 100 invited guests from global companies and venture capital.
< Photo 4. Presentation for AP Lab >
Prior to this event, participating startups will be visiting the New York Economic Development Corporation and large law firms to receive advice on U.S. government support programs and on their attemps to enter the U.S. market. In addition, the participating companies plan to visit a startup support investment institution pursuing sustainable development goals and the Leslie eLab, New York University's one-stop startup support space, to lay the foundation for KAIST's leap forward in global technology commercialization.
< Photo 5. Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation (left) at the 2023 KAIST Tech Fair in New York with the key participants >
Sung-Yool Choi, the Director of KAIST Institute of Technology Value Creation, said, “KAIST prepared this event to realize its vision of being a leading university in creating global value.” He added, “We hope that our startups founded with KAIST technology would successfully completed market verification to be successful in securing global demands and in attracting investments for their endeavors.”
2023.09.11 View 14557 -
KAIST builds a high-resolution 3D holographic sensor using a single mask
Holographic cameras can provide more realistic images than ordinary cameras thanks to their ability to acquire 3D information about objects. However, existing holographic cameras use interferometers that measure the wavelength and refraction of light through the interference of light waves, which makes them complex and sensitive to their surrounding environment.
On August 23, a KAIST research team led by Professor YongKeun Park from the Department of Physics announced a new leap forward in 3D holographic imaging sensor technology.
The team proposed an innovative holographic camera technology that does not use complex interferometry. Instead, it uses a mask to precisely measure the phase information of light and reconstruct the 3D information of an object with higher accuracy.
< Figure 1. Structure and principle of the proposed holographic camera. The amplitude and phase information of light scattered from a holographic camera can be measured. >
The team used a mask that fulfills certain mathematical conditions and incorporated it into an ordinary camera, and the light scattered from a laser is measured through the mask and analyzed using a computer. This does not require a complex interferometer and allows the phase information of light to be collected through a simplified optical system. With this technique, the mask that is placed between the two lenses and behind an object plays an important role. The mask selectively filters specific parts of light,, and the intensity of the light passing through the lens can be measured using an ordinary commercial camera. This technique combines the image data received from the camera with the unique pattern received from the mask and reconstructs an object’s precise 3D information using an algorithm.
This method allows a high-resolution 3D image of an object to be captured in any position. In practical situations, one can construct a laser-based holographic 3D image sensor by adding a mask with a simple design to a general image sensor. This makes the design and construction of the optical system much easier. In particular, this novel technology can capture high-resolution holographic images of objects moving at high speeds, which widens its potential field of application.
< Figure 2. A moving doll captured by a conventional camera and the proposed holographic camera. When taking a picture without focusing on the object, only a blurred image of the doll can be obtained from a general camera, but the proposed holographic camera can restore the blurred image of the doll into a clear image. >
The results of this study, conducted by Dr. Jeonghun Oh from the KAIST Department of Physics as the first author, were published in Nature Communications on August 12 under the title, "Non-interferometric stand-alone single-shot holographic camera using reciprocal diffractive imaging".
Dr. Oh said, “The holographic camera module we are suggesting can be built by adding a filter to an ordinary camera, which would allow even non-experts to handle it easily in everyday life if it were to be commercialized.” He added, “In particular, it is a promising candidate with the potential to replace existing remote sensing technologies.”
This research was supported by the National Research Foundation’s Leader Research Project, the Korean Ministry of Science and ICT’s Core Hologram Technology Support Project, and the Nano and Material Technology Development Project.
2023.09.05 View 6822 -
A KAIST Research Team Produces Eco-Friendly Nylon with Engineered Bacterium
With worsening climate change and environmental issues, in recent years, there has been increased interest in the eco-friendly production of polymers like nylon.
On August 10, Dr. Taehee Han from a KAIST research team led by Distinguished Professor Sang Yup Lee in the Department of Chemical and Biomolecular Engineering revealed the successful development of a microbial strain that produces valerolactam, a monomer of nylon-5.
Valerolactam is an important monomer that constitutes nylon-5 and nylon-6,5. Nylon is the oldest synthetic polymer, and nylon-5 is one of its derivatives composed of monomers with five carbons, while nylon-5,6 is composed of two types of monomers with either five or six carbons. They not only have excellent processability, but are also light and tough, which allows them to be applied in a wide range of industrial sectors including clothing, badminton rackets, fishing nets, tents, and gear parts. Monomers are materials that can be built into polymers, and synthetic processes are what connects them into a polymer.
The chemical production of valerolactam, however, is based on petrochemistry, where extreme reaction conditions are required and toxic waste is produced. To solve these problems, efforts are being made to develop environmentally friendly and highly efficient microbial cell factories for lactam production. Systems metabolic engineering, a key strategy for effective microbial strain development, is a research field pioneered by Professor Sang Yup Lee.
Professor Lee’s team used metabolic engineering, a technique for manipulating microbial metabolic pathways, to construct a synthetic metabolic pathway for valerolactam production in Corynebacteriam glutamicum, a bacterium commonly used for amino acid production. With this, they successfully developed a microbial strain that utilizes biomass-derived glucose as a carbon source to produce high-value valerolactam.
In 2017, the team suggested a novel method that metabolically manipulates Escherichia coli to produce valerolactam. However, there were several limitations at the time including low producibility and the generation of harmful byproducts.
< Figure 1. Schematic graphical representation of the development of microorganisms that produce valerolactam, a nylon-5 monomer >
In this research, the team improved valerolactam producibility and incorporated an additional systems metabolic strategy to the developed microbial strain while eliminating the harmful byproducts. By removing the gene involved in the production of the main byproduct and through gene screening, the team successfully converted 5-aminovaleric acid, a byproduct and a precursor, into valerolactam.
Furthermore, by employing a strategy where the 5-aminovaleric acid-converting gene is inserted multiple times into the genome, the team strengthened the metabolic flux for valerolactam production. As a result, they reached a world-record concentration of 76.1 g/L, which is 6.17 times greater than what was previously reported.
This study was published in Metabolic Engineering on July 12, under the title, “Metabolic engineering of Corynebacterium glutamicum for the high-level production of valerolactam, a nylon-5 monomer”.
Dr. Taehee Han, the first author of the paper, said, “The significance of this research lies in our development of an environmentally friendly technology that efficiently produces monomer lactam for nylon production using microorganisms.” She added, “Through this technology, we will be able to take a step forward in replacing the petrochemical industry with a microorganism-based biopolymer industry.”
This work was supported by the “Development of Next-Generation Biofinery Platform Technologies for Leading Bio-based Chemicals Industry Project” funded by the Korean Ministry of Science and ICT.
2023.08.24 View 5403 -
A KAIST research team identifies a cause of mental diseases induced by childhood abuse
Childhood neglect and/or abuse can induce extreme stress that significantly changes neural networks and functions during growth. This can lead to mental illnesses, including depression and schizophrenia, but the exact mechanism and means to control it were yet to be discovered.
On August 1, a KAIST research team led by Professor Won-Suk Chung from the Department of Biological Sciences announced the identification of excessive synapse removal mediated by astrocytes as the cause of mental diseases induced by childhood abuse trauma. Their research was published in Immunity, a top international journal in the field of immunology.
The research team discovered that the excessive astrocyte-mediated removal of excitatory synapses in the brain in response to stress hormones is a cause of mental diseases induced by childhood neglect and abuse. Clinical data have previously shown that high levels of stress can lead to various mental diseases, but the exact mechanism has been unknown. The results of this research therefore are expected to be widely applied to the prevention and treatment of such diseases.
The research team clinically screened an FDA-approved drug to uncover the mechanism that regulates the phagocytotic role of astrocytes, in which they capture external substances and eliminate them. As a result, the team found that synthetic glucocorticoids, namely stress hormones, enhanced astrocyte-mediated phagocytosis to an abnormal level. Glucocorticoids play essential roles in processes that maintain life, such as carbohydrate metabolism and anti-inflammation, but are also secreted in response to external stimuli such as stress, allowing the body to respond appropriately. However, excessive and long-term exposure to glucocorticoids caused by chronic stress can lead to various mental diseases including depression, cognitive disorders, and anxiety.
< Figure 1. Results of screening for compounds that increase astrocyte phagocytosis
(A) Discovered that synthetic glucocorticoid (stress hormone) increases the phagocytosis of astrocytes through screening of FDA-approved clinical compounds. (B-C) When treated with stress hormones, the phagocytosis of astrocytes is greatly increased, but this phenomenon is strongly suppressed by the GR antagonist (Mifepristone). CORT: corticosterone (stress hormone), Eplerenone: mineralocorticoid receptor (MR) antagonist, Mifepristone: glucocorticoid receptor (GR) antagonist >
To understand the changes in astrocyte functions caused by childhood stress, the research team used mice models with early social deprivation, and discovered that stress hormones bind to the glucocorticoid receptors (GRs) of astrocytes. This significantly increased the expression of Mer tyrosine kinase (MERK), which plays an essential role in astrocyte phagocytosis. Surprisingly, out of the various neurons in the cerebral cortex, astrocytes would eliminate only the excitatory synapses of specific neurons. The team found that this builds abnormal neural networks, which can lead to complex behavioral abnormalities such as social deficiencies and depression in adulthood.
The team also observed that microglia, which also play an important role in cerebral immunity, did not contribute to synapse removal in the mice models with early social deprivation. This confirms that the response to stress hormones during childhood is specifically astrocyte-mediated.
To find out whether these results are also applicable in humans, the research team used a brain organoid grown from human-induced pluripotent stem cells to observe human responses to stress hormones. The team observed that the stress hormones induced astrocyte GRs and phagocyte activation in the human brain organoid as well, and confirmed that the astrocytes subsequently eliminated excessive amounts of excitatory synapses. By showing that mice and humans both showed the same synapse control mechanism in response to stress, the team suggested that this discovery is applicable to mental disorders in humans.
< Figure 2. A schematic diagram of the study published in Immunity. Excessive stress hormone secretion in childhood increases the expression of the MERTK phagocytic receptor through the glucocorticoid receptor (GR) of astrocytes, resulting in excessive elimination of excitatory synapses. Excessive synaptic elimination by astrocytes during brain development causes permanent damage to brain circuits, resulting in abnormal neural activity in the adult brain and psychiatric behaviors such as depression and anti-social tendencies. >
Prof. Won-Suk Chung said, “Until now, we did not know the exact mechanism for how childhood stress caused brain diseases. This research was the first to show that the excessive phagocytosis of astrocytes could be an important cause of such diseases.” He added, “In the future, controlling the immune response of astrocytes will be used as a fundamental target for understanding and treating brain diseases.”
This research, written by co-first authors Youkyeong Byun (Ph.D. candidate) and Nam-Shik Kim (post-doctoral associate) from the KAIST Department of Biological Sciences, was published in the internationally renowned journal Immunity, a sister magazine of Cell and one of the best journal in the field of immunology, on July 31 under the title "Stress induces behavioral abnormalities by increasing expression of phagocytic receptor MERTK in astrocytes to promote synapse phagocytosis."
This work was supported by a National Research Foundation of Korea grant, the Korea Health Industry Development Institute (KHIDI), and the Korea Dementia Research Center (KDRC).
2023.08.04 View 6543 -
KAIST presents a microbial cell factory as a source of eco-friendly food and cosmetic coloring
Despite decades of global population growth, global food crisis seems to be at hand yet again because the food productivity is cut severely due to prolonged presence of abnormal weather from intensifying climate change and global food supply chain is deteriorated due to international conflicts such as wars exacerbating food shortages and nutritional inequality around the globe. At the same time, however, as awareness of the environment and sustainability rises, an increase in demand for more eco-friendly and high-quality food and beauty products is being observed not without a sense of irony. At a time like this, microorganisms are attracting attention as a key that can handle this couple of seemingly distant problems.
KAIST (President Kwang-Hyung Lee) announced on the 26th that Kyeong Rok Choi, a research professor of the Bioprocess Research Center and Sang Yup Lee, a Distinguished Professor of the Department of Chemical and Biomolecular Engineering, published a paper titled “Metabolic Engineering of Microorganisms for Food and Cosmetics Production” upon invitation by “Nature Reviews Bioengineering” to be published online published by Nature after peer review.
※ Paper title: Systems metabolic engineering of microorganisms for food and cosmetics production
※ Author information: Kyeong Rok Choi (first author) and Sang Yup Lee (corresponding author)
Systems metabolic engineering is a research field founded by Distinguished Professor Sang Yup Lee of KAIST to more effectively develop microbial cell factories, the core factor of the next-generation bio industry to replace the existing chemical industry that relies heavily on petroleum. By applying a systemic metabolic engineering strategy, the researchers have developed a number of high-performance microbial cell factories that produce a variety of food and cosmetic compounds including natural substances like heme and zinc protoporphyrin IX compounds which can improve the flavor and color of synthetic meat, lycopene and β-carotene which are functional natural pigments that can be widely used in food and cosmetics, and methyl anthranilate, a grape-derived compound widely used to impart grape flavor in food and beverage manufacturing.
In this paper written upon invitation by Nature, the research team covered remarkable cases of microbial cell factory that can produce amino acids, proteins, fats and fatty acids, vitamins, flavors, pigments, alcohols, functional compounds and other food additives used in various foods and cosmetics and the companies that have successfully commercialized these microbial-derived materials Furthermore, the paper organized and presents systems metabolic engineering strategies that can spur the development of industrial microbial cell factories that can produce more diverse food and cosmetic compounds in an eco-friendly way with economic feasibility.
< Figure 1. Examples of production of food and cosmetic compounds using microbial cell factories >
For example, by producing proteins or amino acids with high nutritional value through non-edible biomass used as animal feed or fertilizer through the microbial fermentation process, it will contribute to the increase in production and stable supply of food around the world. Furthermore, by contributing to developing more viable alternative meat, further reducing dependence on animal protein, it can also contribute to reducing greenhouse gases and environmental pollution generated through livestock breeding or fish farming.
In addition, vanillin or methyl anthranilate, which give off vanilla or grape flavor, are widely added to various foods, but natural products isolated and refined from plants are low in production and high in production cost, so in most cases, petrochemicals substances derived from vanillin and methylanthranilic acid are added to food. These materials can also be produced through an eco-friendly and human-friendly method by borrowing the power of microorganisms.
Ethical and resource problems that arise in producing compounds like Calmin (cochineal pigment), a coloring added to various cosmetics and foods such as red lipstick and strawberry-flavored milk, which must be extracted from cochineal insects that live only in certain cacti. and Hyaluronic acid, which is widely consumed as a health supplement, but is only present in omega-3 fatty acids extracted from shark or fish livers, can also be resolved when they can be produced in an eco-friendly way using microorganisms.
KAIST Research Professor Kyeong Rok Choi, the first author of this paper, said, “In addition to traditional fermented foods such as kimchi and yogurt, foods produced with the help of microorganisms like cocoa butter, a base ingredient for chocolate that can only be obtained from fermented cacao beans, and monosodium glutamate, a seasoning produced through microbial fermentation are already familiar to us”. “In the future, we will be able to acquire a wider variety of foods and cosmetics even more easily produced in an eco-friendly and sustainable way in our daily lives through microbial cell factories.” he added.
< Figure 2. Systems metabolic engineering strategy to improve metabolic flow in microbial cell factories >
Distinguished Professor Sang Yup Lee said, “It is engineers’ mission to make the world a better place utilizing science and technology.” and added, “Continuous advancement and active use of systems metabolic engineering will contribute greatly to easing and resolving the problems arising from both the food crisis and the climate change."
This research was carried out as a part of the “Development of Protein Production Technology from Inorganic Substances through Control of Microbial Metabolism System Project” (Project Leader: Kyeong Rok Choi, KAIST Research Professor) of the the Center for Agricultural Microorganism and Enzyme (Director Pahn-Shick Chang) supported by the Rural Development Administration and the “Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project” (Project Leader: Sang Yup Lee, KAIST Distinguished Professor) of the Petroleum-Substitute Eco-friendly Chemical Technology Development Program supported by the Ministry of Science and ICT.
2023.07.28 View 7705 -
A KAIST research team develops a washable, transparent, and flexible OLED with MXene nanotechnology
Transparent and flexible displays, which have received a lot of attention in various fields including automobile displays, bio-healthcare, military, and fashion, are in fact known to break easily when experiencing small deformations. To solve this problem, active research is being conducted on many transparent and flexible conductive materials such as carbon nanotubes, graphene, silver nanowires, and conductive polymers.
On June 13, a joint research team led by Professor Kyung Cheol Choi from the KAIST School of Electrical Engineering and Dr. Yonghee Lee from the National Nano Fab Center (NNFC) announced the successful development of a water-resistant, transparent, and flexible OLED using MXene nanotechnology. The material can emit and transmit light even when exposed to water.
MXene is a 2D material with high electrical conductivity and optical transmittance, and it can be produced on a large scale through solution processes. However, despite these attractive properties, MXene’s applications were limited as a long-term electrical device due to its electrical properties being degraded easily by atmospheric moisture and water. The material was therefore unable to be systemized into the form of a matrix that can display information.
Professor Choi’s research team used an encapsulation tactic that can protect materials from oxidation caused by moisture and oxygen to develop a MXene-based OLED with a long lifespan and high stability against external environmental factors. The research team first focused on analyzing the degradation mechanism of MXene’s electrical conductivity, and then concentrated on designing an encapsulation membrane. The team blocked moisture and provided flexibility through residual stress offset, ultimately producing a double-layered encapsulation membrane. In addition, a thin plastic film with a thickness of a few micrometers was attached to the top layer to allow washing in water without degradation.
< Figure 1. (a) Transparent passive-matrix display made of MXene-based OLED, (b) Cross-sectional image of MXene-based OLED observed by transmission electron microscope (TEM), (c) Electro-optical characteristic graph of red, green, and blue MXene-based OLED >
Through this study, the research team developed a MXene-based red(R)/green(G)/blue(B) OLED that emits a brightness of over 1,000 cd/m2 that is detectable by the naked eye even under sunlight, thereby meeting the conditions for outdoor displays. As for the red MXene-based OLED, the researchers confirmed a standby storage life of 2,000 hours (under 70% luminescence), a standby operation life of 1,500 hours (under 60% luminescence), and a flexibility withstanding 1,000 cycles under a low curvature of under 1.5mm. In addition, they showed that its performance was maintained even after six hours of immersion under water (under 80% luminescence). Furthermore, a patterning technique was used to produce the MXene-based OLED in the form of a passive matrix, and the team demonstrated its use as a transparent display by displaying letters and shapes.
Ph.D. candidate So Yeong Jeong, who led this study, said, “To improve the reliability of MXene OLED, we focused on producing an adequate encapsulation structure and a suitable process design.” She added, “By producing a matrix-type MXene OLED and displaying simple letters and shapes, we have laid the foundations for MXene’s application in the field of transparent displays.”
< Image 1. Cover of ACS Nano Front Cover (Conceptual diagram of MXene-based OLED display) >
Professor Choi said, “This research will become the guideline for applying MXene in electrical devices, but we expect for it to also be applied in other fields that require flexible and transparent displays like automobiles, fashion, and functional clothing. And to widen the gap with China’s OLED technology, these new OLED convergence technologies must continue to be developed.”
This research was supported by the National Research Foundation of Korea and funded by the Ministry of Science and ICT, Korea. It was published as a front cover story of ACS Nano under the title, “Highly Air-Stable, Flexible, and Water-Resistive 2D Titanium Carbide MXene-Based RGB Organic Light-Emitting Diode Displays for Transparent Free-Form Electronics” on June 13.
2023.07.10 View 6218 -
A KAIST Research Team Identifies a Cancer Reversion Mechanism
Despite decades of intensive cancer research by numerous biomedical scientists, cancer still holds its place as the number one cause of death in Korea. The fundamental reason behind the limitations of current cancer treatment methods is the fact that they all aim to completely destroy cancer cells, which eventually allows the cancer cells to acquire immunity. In other words, recurrences and side-effects caused by the destruction of healthy cells are inevitable. To this end, some have suggested anticancer treatment methods based on cancer reversion, which can revert cancer cells back to normal or near-normal cells under certain conditions. However, the practical development of this idea has not yet been attempted.
On June 8, a KAIST research team led by Professor Kwang-Hyun Cho from the Department of Bio and Brain Engineering reported to have successfully identified the fundamental principle of a process that can revert cancer cells back to normal cells without killing the cells.
Professor Cho’s team focused on the fact that unlike normal cells, which react according to external stimuli, cancer cells tend to ignore such stimuli and only undergo uncontrolled cell division. Through computer simulation analysis, the team discovered that the input-output (I/O) relationships that were distorted by genetic mutations could be reverted back to normal I/O relationships under certain conditions. The team then demonstrated through molecular cell experiments that such I/O relationship recovery also occurred in real cancer cells.
The results of this study, written by Dr. Jae Il Joo and Dr. Hwa-Jeong Park, were published in Wiley’s Advanced Science online on June 2 under the title, "Normalizing input-output relationships of cancer networks for reversion therapy."
< Image 1. Input-output (I/O) relationships in gene regulatory networks >
Professor Kwang-Hyun Cho's research team classified genes into four types by simulation-analyzing the effect of gene mutations on the I/O relationship of gene regulatory networks. (Figure A-J) In addition, by analyzing 18 genes of the cancer-related gene regulatory network, it was confirmed that when mutations occur in more than half of the genes constituting each network, reversibility is possible through appropriate control. (Figure K)
Professor Cho’s team uncovered that the reason the distorted I/O relationships of cancer cells could be reverted back to normal ones was the robustness and redundancy of intracellular gene control networks that developed over the course of evolution. In addition, they found that some genes were more promising as targets for cancer reversion than others, and showed through molecular cell experiments that controlling such genes could revert the distorted I/O relationships of cancer cells back to normal ones.
< Image 2. Simulation results of restoration of bladder cancer gene regulation network and I/O relationship of bladder cancer cells. >
The research team classified the effects of gene mutations on the I/O relationship in the bladder cancer gene regulation network by simulation analysis and classified them into 4 types. (Figure A) Through this, it was found that the distorted input-output relationship between bladder cancer cell lines KU-1919 and HCT-1197 could be restored to normal. (Figure B)
< Image 3. Analysis of survival of bladder cancer patients according to reversible gene mutation and I/O recovery experiment of bladder cancer cells. >
As predicted through network simulation analysis, Professor Kwang-Hyun Cho's research team confirmed through molecular cell experiments that the response to TGF-b was normally restored when AKT and MAP3K1 were inhibited in the bladder cancer cell line KU-1919. (Figure A-G) In addition, it was confirmed that there is a difference in the survival rate of bladder cancer patients depending on the presence or absence of a reversible gene mutation. (Figure H)
The results of this research show that the reversion of real cancer cells does not happen by chance, and that it is possible to systematically explore targets that can induce this phenomenon, thereby creating the potential for the development of innovative anticancer drugs that can control such target genes.
< Image 4. Cancer cell reversibility principle >
The research team analyzed the reversibility, redundancy, and robustness of various networks and found that there was a positive correlation between them. From this, it was found that reversibility was additionally inherent in the process of evolution in which the gene regulatory network acquired redundancy and consistency.
Professor Cho said, “By uncovering the fundamental principles of a new cancer reversion treatment strategy that may overcome the unresolved limitations of existing chemotherapy, we have increased the possibility of developing new and innovative drugs that can improve both the prognosis and quality of life of cancer patients.”
< Image 5. Conceptual diagram of research results >
The research team identified the fundamental control principle of cancer cell reversibility through systems biology research. When the I/O relationship of the intracellular gene regulatory network is distorted by mutation, the distorted I/O relationship can be restored to a normal state by identifying and adjusting the reversible gene target based on the redundancy of the molecular circuit inherent in the complex network.
After Professor Cho’s team first suggested the concept of reversion treatment, they published their results for reverting colorectal cancer in January 2020, and in January 2022 they successfully re-programmed malignant breast cancer cells back into hormone-treatable ones. In January 2023, the team successfully removed the metastasis ability from lung cancer cells and reverted them back to a state that allowed improved drug reactivity. However, these results were case studies of specific types of cancer and did not reveal what common principle allowed cancer reversion across all cancer types, making this the first revelation of the general principle of cancer reversion and its evolutionary origins.
This research was funded by the Ministry of Science and ICT of the Republic of Korea and the National Research Foundation of Korea.
2023.06.20 View 9743 -
MVITRO Co., Ltd. Signs to Donate KRW 1 Billion as Development Fund toward KAIST-NYU Joint Campus
KAIST (President Kwang Hyung Lee) announced on the 29th that it has solicited a development fund of KRW 1 billion from MVITRO (CEO Young Woo Lee) for joint research at the KAIST-NYU Joint Campus, which is being pursued to be KAIST's first campus on the United States.
KAIST plans to use this development fund for research and development of various solutions in the field of 'Healthcare at Home' among several joint researches being conducted with New York University (hereinafter referred to as NYU).
Young Woo Lee, the CEO of MVITRO, said, "We decided to make the donation with the hope that the KAIST-NYU Joint Campus will become an ecosystem that would help with Korean companies’ advancement into the US."
After announcing its plans to enter New York in 2021, KAIST has formed partnerships with NYU and New York City last year. Currently, NYU and KAIST are devising plans for mid- to long-term joint research in nine fields of studies including AI and bio-medicine and technology, and are promoting cooperation in the field of education, including exchange students, minors, double majors, and joint degrees under the joint campus agreement,
The ceremony for the consigning of MVITRO Co., Ltd.’s donation was held at the main campus of KAIST in the afternoon of the 29th and was attended by KAIST officials such as President Kwang Hyung Lee and Jae-Hung Han, the executive director of KAIST Development Foundation, along with the NYU President-Designate Linda G. Mills, and the CEO of MVITRO, Young Woo Lee.
< Photo. (from left) Kwang Hyung Lee, the President of KAIST, Linda G. Mills, the President-Designate of NYU, and Young Woo Lee, the CEO of MVITRO, pose for the photo with the signed letter of donation on May 29, 2023 at KAIST >
Linda Mills, the nominee designated to be NYU president next term said, “I am proud to join our colleagues in celebrating this important gift from MVITRO, which will help support the partnership between KAIST and NYU. This global partnership leverages the distinctive strengths of both universities to drive advances in research poised to deliver profound impact, such as the intersections of healthcare, technology, and AI."
President Kwang Hyung Lee said, "The KAIST-NYU Joint Campus will be the first step in extending KAIST's excellent science and technology capabilities to the international stage and will serve as a bridgehead to help excellent technological advancements venture into the United States." Then, President Lee added, "I would like to express my gratitude to MVITRO for sympathizing with this vision. I will work with NYU to lead the creation of global values.”
On a different note, MVITRO Co., Ltd., is a home medical device maker that collaborated with Hyundai Futurenet Co., Ltd. to develop an IoT product that combined a painless laser lancet (blood collector) and a blood glucose meter into one for a convenient at-home health support, which received favorable reviews from overseas buyers at CES 2023.
2023.05.30 View 8405