research
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KAIST researchers find sleep delays more prevalent in countries of particular culture than others
Sleep has a huge impact on health, well-being and productivity, but how long and how well people sleep these days has not been accurately reported. Previous research on how much and how well we sleep has mostly relied on self-reports or was confined within the data from the unnatural environments of the sleep laboratories.
So, the questions remained: Is the amount and quality of sleep purely a personal choice? Could they be independent from social factors such as culture and geography?
< From left to right, Sungkyu Park of Kangwon National University, South Korea; Assem Zhunis of KAIST and IBS, South Korea; Marios Constantinides of Nokia Bell Labs, UK; Luca Maria Aiello of the IT University of Copenhagen, Denmark; Daniele Quercia of Nokia Bell Labs and King's College London, UK; and Meeyoung Cha of IBS and KAIST, South Korea >
A new study led by researchers at Korea Advanced Institute of Science and Technology (KAIST) and Nokia Bell Labs in the United Kingdom investigated the cultural and individual factors that influence sleep. In contrast to previous studies that relied on surveys or controlled experiments at labs, the team used commercially available smartwatches for extensive data collection, analyzing 52 million logs collected over a four-year period from 30,082 individuals in 11 countries. These people wore Nokia smartwatches, which allowed the team to investigate country-specific sleep patterns based on the digital logs from the devices.
< Figure comparing survey and smartwatch logs on average sleep-time, wake-time, and sleep durations. Digital logs consistently recorded delayed hours of wake- and sleep-time, resulting in shorter sleep durations. >
Digital logs collected from the smartwatches revealed discrepancies in wake-up times and sleep-times, sometimes by tens of minutes to an hour, from the data previously collected from self-report assessments. The average sleep-time overall was calculated to be around midnight, and the average wake-up time was 7:42 AM. The team discovered, however, that individuals' sleep is heavily linked to their geographical location and cultural factors. While wake-up times were similar, sleep-time varied by country. Individuals in higher GDP countries had more records of delayed bedtime. Those in collectivist culture, compared to individualist culture, also showed more records of delayed bedtime. Among the studied countries, Japan had the shortest total sleep duration, averaging a duration of under 7 hours, while Finland had the longest, averaging 8 hours.
Researchers calculated essential sleep metrics used in clinical studies, such as sleep efficiency, sleep duration, and overslept hours on weekends, to analyze the extensive sleep patterns. Using Principal Component Analysis (PCA), they further condensed these metrics into two major sleep dimensions representing sleep quality and quantity. A cross-country comparison revealed that societal factors account for 55% of the variation in sleep quality and 63% of the variation in sleep quantity.
Countries with a higher individualism index (IDV), which placed greater emphasis on individual achievements and relationships, had significantly longer sleep durations, which could be attributed to such societies having a norm of going to bed early. Spain and Japan, on the other hand, had the bedtime scheduled at the latest hours despite having the highest collectivism scores (low IDV). The study also discovered a moderate relationship between a higher uncertainty avoidance index (UAI), which measures implementation of general laws and regulation in daily lives of regular citizens, and better sleep quality.
Researchers also investigated how physical activity can affect sleep quantity and quality to see if individuals can counterbalance cultural influences through personal interventions. They discovered that increasing daily activity can improve sleep quality in terms of shortened time needed in falling asleep and waking up. Individuals who exercise more, however, did not sleep longer. The effect of exercise differed by country, with more pronounced effects observed in some countries, such as the United States and Finland. Interestingly, in Japan, no obvious effect of exercise could be observed. These findings suggest that the relationship between daily activity and sleep may differ by country and that different exercise regimens may be more effective in different cultures.
This research published on the Scientific Reports by the international journal, Nature, sheds light on the influence of social factors on sleep. (Paper Title "Social dimensions impact individual sleep quantity and quality" Article number: 9681)
One of the co-authors, Daniele Quercia, commented: “Excessive work schedules, long working hours, and late bedtime in high-income countries and social engagement due to high collectivism may cause bedtimes to be delayed.”
Commenting on the research, the first author Shaun Sungkyu Park said, "While it is intriguing to see that a society can play a role in determining the quantity and quality of an individual's sleep with large-scale data, the significance of this study is that it quantitatively shows that even within the same culture (country), individual efforts such as daily exercise can have a positive impact on sleep quantity and quality."
"Sleep not only has a great impact on one’s well-being but it is also known to be associated with health issues such as obesity and dementia," said the lead author, Meeyoung Cha. "In order to ensure adequate sleep and improve sleep quality in an aging society, not only individual efforts but also a social support must be provided to work together," she said. The research team will contribute to the development of the high-tech sleep industry by making a code that easily calculates the sleep indicators developed in this study available free of charge, as well as providing the benchmark data for various types of sleep research to follow.
2023.07.07 View 6666 -
Synthetic sRNAs to knockdown genes in medical and industrial bacteria
Bacteria are intimately involved in our daily lives. These microorganisms have been used in human history for food such as cheese, yogurt, and wine, In more recent years, through metabolic engineering, microorganisms been used extensively as microbial cell factories to manufacture plastics, feed for livestock, dietary supplements, and drugs. However, in addition to these bacteria that are beneficial to human lives, pathogens such as Pneumonia, Salmonella, and Staphylococcus that cause various infectious diseases are also ubiquitously present. It is important to be able to metabolically control these beneficial industrial bacteria for high value-added chemicals production and to manipulate harmful pathogens to suppress its pathogenic traits.
KAIST (President Kwang Hyung Lee) announced on the 10th that a research team led by Distinguished Professor Sang Yup Lee of the Department of Biochemical Engineering has developed a new sRNA tool that can effectively inhibit target genes in various bacteria, including both Gram-negative and Gram-positive bacteria. The research results were published online on April 24 in Nature Communications.
※ Thesis title: Targeted and high-throughput gene knockdown in diverse bacteria using synthetic sRNAs
※ Author information : Jae Sung Cho (co-1st), Dongsoo Yang (co-1st), Cindy Pricilia Surya Prabowo (co-author), Mohammad Rifqi Ghiffary (co-author), Taehee Han (co-author), Kyeong Rok Choi (co-author), Cheon Woo Moon (co-author), Hengrui Zhou (co-author), Jae Yong Ryu (co-author), Hyun Uk Kim (co-author) and Sang Yup Lee (corresponding author).
sRNA is an effective tool for synthesizing and regulating target genes in E. coli, but it has been difficult to apply to industrially useful Gram-positive bacteria such as Bacillus subtilis and Corynebacterium in addition to Gram-negative bacteria such as E. coli.
To address this issue, a research team led by Distinguished Professor Lee Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST developed a new sRNA platform that can effectively suppress target genes in various bacteria, including both Gram-negative and positive bacteria. The research team surveyed thousands of microbial-derived sRNA systems in the microbial database, and eventually designated the sRNA system derived from 'Bacillus subtilis' that showed the highest gene knockdown efficiency, and designated it as “Broad-Host-Range sRNA”, or BHR-sRNA.
A similar well-known system is the CRISPR interference (CRISPRi) system, which is a modified CRISPR system that knocks down gene expression by suppressing the gene transcription process. However, the Cas9 protein in the CRISPRi system has a very high molecular weight, and there have been reports growth inhibition in bacteria. The BHR-sRNA system developed in this study did not affect bacterial growth while showing similar gene knockdown efficiencies to CRISPRi.
< Figure 1. a) Schematic illustration demonstrating the mechanism of syntetic sRNA b) Phylogenetic tree of the 16 Gram-negative and Gram-positive bacterial species tested for gene knockdown by the BHR-sRNA system. >
To validate the versatility of the BHR-sRNA system, 16 different gram-negative and gram-positive bacteria were selected and tested, where the BHR-sRNA system worked successfully in 15 of them. In addition, it was demonstrated that the gene knockdown capability was more effective than that of the existing E. coli-based sRNA system in 10 bacteria. The BHR-sRNA system proved to be a universal tool capable of effectively inhibiting gene expression in various bacteria.
In order to address the problem of antibiotic-resistant pathogens that have recently become more serious, the BHR-sRNA was demonstrated to suppress the pathogenicity by suppressing the gene producing the virulence factor. By using BHR-sRNA, biofilm formation, one of the factors resulting in antibiotic resistance, was inhibited by 73% in Staphylococcus epidermidis a pathogen that can cause hospital-acquired infections. Antibiotic resistance was also weakened by 58% in the pneumonia causing bacteria Klebsiella pneumoniae. In addition, BHR-sRNA was applied to industrial bacteria to develop microbial cell factories to produce high value-added chemicals with better production performance. Notably, superior industrial strains were constructed with the aid of BHR-sRNA to produce the following chemicals: valerolactam, a raw material for polyamide polymers, methyl-anthranilate, a grape-flavor food additive, and indigoidine, a blue-toned natural dye.
The BHR-sRNA developed through this study will help expedite the commercialization of bioprocesses to produce high value-added compounds and materials such as artificial meat, jet fuel, health supplements, pharmaceuticals, and plastics. It is also anticipated that to help eradicating antibiotic-resistant pathogens in preparation for another upcoming pandemic. “In the past, we could only develop new tools for gene knockdown for each bacterium, but now we have developed a tool that works for a variety of bacteria” said Distinguished Professor Sang Yup Lee.
This work was supported by the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project from NRF supported by the Korean MSIT.
2023.05.10 View 6539 -
A biohybrid system to extract 20 times more bioplastic from CO2 developed by KAIST researchers
As the issues surrounding global climate change intensify, more attention and determined efforts are required to re-grasp the issue as a state of “crisis” and respond to it properly. Among the various methods of recycling CO2, the electrochemical CO2 conversion technology is a technology that can convert CO2 into useful chemical substances using electrical energy. Since it is easy to operate facilities and can use the electricity from renewable sources like the solar cells or the wind power, it has received a lot of attention as an eco-friendly technology can contribute to reducing greenhouse gases and achieve carbon neutrality.
KAIST (President Kwang Hyung Lee) announced on the 30th that the joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering succeeded in developing a technology that produces bioplastics from CO2 with high efficiency by developing a hybrid system that interlinked the electrochemical CO2 conversion and microbial bio conversion methods together. The results of the research, which showed the world's highest productivity by more than 20 times compared to similar systems, were published online on March 27th in the "Proceedings of the National Academy of Sciences (PNAS)".
※ Paper title: Biohybrid CO2 electrolysis for the direct synthesis of polyesters from CO2
※ Author information: Jinkyu Lim (currently at Stanford Linear Accelerator Center, co-first author), So Young Choi (KAIST, co-first author), Jae Won Lee (KAIST, co-first author), Hyunjoo Lee (KAIST, corresponding author), Sang Yup Lee (KAIST, corresponding author)
For the efficient conversion of CO2, high-efficiency electrode catalysts and systems are actively being developed. As conversion products, only compounds containing one or up to three carbon atoms are produced on a limited basis. Compounds of one carbon, such as CO, formic acid, and ethylene, are produced with relatively high efficiency. Liquid compounds of several carbons, such as ethanol, acetic acid, and propanol, can also be produced by these systems, but due to the nature of the chemical reaction that requires more electrons, there are limitations involving the conversion efficiency and the product selection.
Accordingly, a joint research team led by Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST developed a technology to produce bioplastics from CO2 by linking electrochemical conversion technology with bioconversion method that uses microorganisms.
This electrochemical-bio hybrid system is in the form of having an electrolyzer, in which electrochemical conversion reactions occur, connected to a fermenter, in which microorganisms are cultured. When CO2 is converted to formic acid in the electrolyzer, and it is fed into the fermenter in which the microbes like the Cupriavidus necator, in this case, consumes the carbon source to produce polyhydroxyalkanoate (PHA), a microbial-derived bioplastic.
According to the research results of the existing hybrid concepts, there was a disadvantage of having low productivity or stopping at a non-continuous process due to problems of low efficiency of the electrolysis and irregular results arising from the culturing conditions of the microbes.
In order to overcome these problems, the joint research team made formic acid with a gas diffusion electrode using gaseous CO2. In addition, the team developed a 'physiologically compatible catholyte' that can be used as a culture medium for microorganisms as well as an electrolyte that allows the electrolysis to occur sufficiently without inhibiting the growth of microorganisms, without having to have a additional separation and purification process, which allowed the acide to be supplied directly to microorganisms.
Through this, the electrolyte solution containing formic acid made from CO2 enters the fermentation tank, is used for microbial culture, and enters the electrolyzer to be circulated, maximizing the utilization of the electrolyte solution and remaining formic acid. In addition, a filter was installed to ensure that only the electrolyte solution with any and all microorganisms that can affect the electrosis filtered out is supplied back to the electrolyzer, and that the microorganisms exist only in the fermenter, designing the two system to work well together with utmost efficiency.
Through the developed hybrid system, the produced bioplastic, poly-3-hydroxybutyrate (PHB), of up to 83% of the cell dry weight was produced from CO2, which produced 1.38g of PHB from a 4 cm2 electrode, which is the world's first gram(g) level production and is more than 20 times more productive than previous research. In addition, the hybrid system is expected to be applied to various industrial processes in the future as it shows promises of the continuous culture system.
The corresponding authors, Professor Hyunjoo Lee and Distinguished Professor Sang Yup Lee noted that “The results of this research are technologies that can be applied to the production of various chemical substances as well as bioplastics, and are expected to be used as key parts needed in achieving carbon neutrality in the future.”
This research was received and performed with the supports from the CO2 Reduction Catalyst and Energy Device Technology Development Project, the Heterogeneous Atomic Catalyst Control Project, and the Next-generation Biorefinery Source Technology Development Project to lead the Biochemical Industry of the Oil-replacement Eco-friendly Chemical Technology Development Program by the Ministry of Science and ICT.
Figure 1. Schematic diagram and photo of the biohybrid CO2 electrolysis system.
(A) A conceptual scheme and (B) a photograph of the biohybrid CO2 electrolysis system. (C) A detailed scheme of reaction inside the system. Gaseous CO2 was converted to formate in the electrolyzer, and the formate was converted to PHB by the cells in the fermenter. The catholyte was developed so that it is compatible with both CO2 electrolysis and fermentation and was continuously circulated.
2023.03.30 View 9032 -
KAIST leads AI-based analysis on drug-drug interactions involving Paxlovid
KAIST (President Kwang Hyung Lee) announced on the 16th that an advanced AI-based drug interaction prediction technology developed by the Distinguished Professor Sang Yup Lee's research team in the Department of Biochemical Engineering that analyzed the interaction between the PaxlovidTM ingredients that are used as COVID-19 treatment and other prescription drugs was published as a thesis. This paper was published in the online edition of 「Proceedings of the National Academy of Sciences of America」 (PNAS), an internationally renowned academic journal, on the 13th of March.
* Thesis Title: Computational prediction of interactions between Paxlovid and prescription drugs (Authored by Yeji Kim (KAIST, co-first author), Jae Yong Ryu (Duksung Women's University, co-first author), Hyun Uk Kim (KAIST, co-first author), and Sang Yup Lee (KAIST, corresponding author))
In this study, the research team developed DeepDDI2, an advanced version of DeepDDI, an AI-based drug interaction prediction model they developed in 2018. DeepDDI2 is able to compute for and process a total of 113 drug-drug interaction (DDI) types, more than the 86 DDI types covered by the existing DeepDDI.
The research team used DeepDDI2 to predict possible interactions between the ingredients (ritonavir, nirmatrelvir) of Paxlovid*, a COVID-19 treatment, and other prescription drugs. The research team said that while among COVID-19 patients, high-risk patients with chronic diseases such as high blood pressure and diabetes are likely to be taking other drugs, drug-drug interactions and adverse drug reactions for Paxlovid have not been sufficiently analyzed, yet. This study was pursued in light of seeing how continued usage of the drug may lead to serious and unwanted complications.
* Paxlovid: Paxlovid is a COVID-19 treatment developed by Pfizer, an American pharmaceutical company, and received emergency use approval (EUA) from the US Food and Drug Administration (FDA) in December 2021.
The research team used DeepDDI2 to predict how Paxrovid's components, ritonavir and nirmatrelvir, would interact with 2,248 prescription drugs. As a result of the prediction, ritonavir was predicted to interact with 1,403 prescription drugs and nirmatrelvir with 673 drugs.
Using the prediction results, the research team proposed alternative drugs with the same mechanism but low drug interaction potential for prescription drugs with high adverse drug events (ADEs). Accordingly, 124 alternative drugs that could reduce the possible adverse DDI with ritonavir and 239 alternative drugs for nirmatrelvir were identified.
Through this research achievement, it became possible to use an deep learning technology to accurately predict drug-drug interactions (DDIs), and this is expected to play an important role in the digital healthcare, precision medicine and pharmaceutical industries by providing useful information in the process of developing new drugs and making prescriptions.
Distinguished Professor Sang Yup Lee said, "The results of this study are meaningful at times like when we would have to resort to using drugs that are developed in a hurry in the face of an urgent situations like the COVID-19 pandemic, that it is now possible to identify and take necessary actions against adverse drug reactions caused by drug-drug interactions very quickly.”
This research was carried out with the support of the KAIST New-Deal Project for COVID-19 Science and Technology and the Bio·Medical Technology Development Project supported by the Ministry of Science and ICT.
Figure 1. Results of drug interaction prediction between Paxlovid ingredients and representative approved drugs using DeepDDI2
2023.03.16 View 7197 -
Overview of the 30-year history of metabolic engineering
< Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST >
A research team comprised of Gi Bae Kim, Dr. So Young Choi, Dr. In Jin Cho, Da-Hee Ahn, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST reported the 30-year history of metabolic engineering, highlighting examples of recent progress in the field and contributions to sustainability and health. Their paper “Metabolic engineering for sustainability and health” was published online in the 40th anniversary special issue of Trends in Biotechnology on January 10, 2023.
Metabolic engineering, a discipline of engineering that modifies cell phenotypes through molecular and genetic-level manipulations to improve cellular activities, has been studied since the early 1990s, and has progressed significantly over the past 30 years. In particular, metabolic engineering has enabled the engineering of microorganisms for the development of microbial cell factories capable of efficiently producing chemicals and materials as well as degrading recalcitrant contaminants.
This review article revisited how metabolic engineering has advanced over the past 30 years, from the advent of genetic engineering techniques such as recombinant DNA technologies to recent breakthroughs in systems metabolic engineering and data science aided by artificial intelligence. The research team highlighted momentous events and achievements in metabolic engineering, providing both trends and future directions in the field. Metabolic engineering’s contributions to bio-based sustainable chemicals and clean energy, health, and bioremediation were also reviewed. Finally, the research team shared their perspectives on the future challenges impacting metabolic engineering than must be overcome in order to achieve advancements in sustainability and health.
Distinguished Professor Sang Yup Lee said, “Replacing fossil resource-based chemical processes with bio-based sustainable processes for the production of chemicals, fuels, and materials using metabolic engineering has become our essential task for the future. By looking back on the 30+ years of metabolic engineering, we aimed to highlight the contributions of metabolic engineering to achieve sustainability and good health.” He added, “Metabolic engineering will play an increasingly important role as a key solution to the climate crisis, environmental pollution, food and energy shortages, and health problems in aging societies.”
< Figure: Metabolic Engineering Timeline >
2023.01.25 View 9383 -
KAIST’s unmanned racing car to race in the Indy Autonomous Challenge @ CES 2023 as the only contender representing Asia
- Professor David Hyunchul Shim of the School of Electrical Engineering, is at the Las Vegas Motor Speedway in Las Vegas, Nevada with his students of the Unmanned Systems Research Group (USRG), participating in the Indy Autonomous Challenge (IAC) @ CES as the only Asian team in the race.
Photo 1. Nine teams that competed at the first Indy Autonomous Challenge on October 23, 2021. (KAIST team is the right most team in the front row)
- The EE USRG team won the slot to race in the IAC @ CES 2023 rightly as the semifinals entree of the IAC @ CES 2022’ held in January of last year
- Through the partnership with Hyundai Motor Company, USRG received support to participate in the competition, and is to share the latest developments and trends of the technology with the company researchers
- With upgrades from last year, USRG is to race with a high-speed Indy racing car capable of driving up to 300 km/h and the technology developed in the process is to be used in further advancement of the high-speed autonomous vehicle technology of the future.
KAIST (President Kwang Hyung Lee) announced on the 5th that it will participate in the “Indy Autonomous Challenge (IAC) @ CES 2023”, an official event of the world's largest electronics and information technology exhibition held every year in Las Vegas, Nevada, of the United States from January 5th to 8th.
Photo 2. KAIST Racing Team participating in the Indy Autonomous Challenge @ CES 2023 (Team Leader: Sungwon Na, Team Members: Seongwoo Moon, Hyunwoo Nam, Chanhoe Ryu, Jaeyoung Kang)
“IAC @ CES 2023”, which is to be held at the Las Vegas Motor Speedway (LVMS) on January 7, seeks to advance technology developed as the result of last year's competition to share the results of such advanced high-speed autonomous vehicle technology with the public.
This competition is the 4th competition following the “Indy Autonomous Challenge (IAC)” held for the first time in Indianapolis, USA on October 23, 2021. At the IAC @ CES 2022 following the first IAC competition, the Unmmaned Systems Research Group (USRG) team led by Professor David Hyunchul Shim advanced to the semifinals out of a total of nine teams and won a spot to participate in CES 2023. As a result, the USRG comes into the challenge as the only Asian team to compete with other teams comprised of students and researchers of American and European backgrounds where the culture of motorsports is more deep-rooted.
For CES 2022, Professor David Hyunchul Shim’s research team was able to successfully develop a software that controlled the racing car to comply with the race flags and regulations while going up to 240 km/h all on its on.
Photo 3. KAIST Team’s vehicle on Las Vegas Motor Speedway during the IAC @ CES 2022
In the IAC @ CES 2023, the official racing vehicle AV-23, is a converted version of IL-15, the official racing car for Indy 500, fully automated while maintaining the optimal design for high-speed racing, and was upgraded from the last year’s competition taking up the highest speed up to 300 km/h.
This year’s competition, will develop on last year’s head-to-head autonomous racing and take the form of the single elimination tournament to have the cars overtake the others without any restrictions on the driving course, which would have the team that constantly drives at the fastest speed will win the competition.
Photo 4. KAIST Team’s vehicle overtaking the Italian team, PoliMOVE’s vehicle during one of the race in the IAC @ CES 2022
Professor Shim's team further developed on the CES 2022 certified software to fine tune the external recognition mechanisms and is now focused on precise positioning and driving control technology that factors into maintaining stability even when driving at high speed.
Professor Shim's research team won the Autonomous Driving Competition hosted by Hyundai Motor Company in 2021. Starting with this CES 2023 competition, they signed a partnership contract with Hyundai to receive financial support to participate in the CES competition and share the latest developments and trends of autonomous driving technology with Hyundai Motor's research team.
During CES 2023, the research team will also participate in other events such as the exhibition by the KAIST racing team at the IAC’s official booth located in the West Hall.
Professor David Hyunchul Shim said, “With these competitions being held overseas, there were many difficulties having to keep coming back, but the students took part in it diligently, for which I am deeply grateful. Thanks to their efforts, we were able to continue in this competition, which will be a way to verify the autonomous driving technology that we developed ourselves over the past 13 years, and I highly appreciate that.”
“While high-speed autonomous driving technology is a technology that is not yet sought out in Korea, but it can be applied most effectively for long-distance travel in the Korea,” he went on to add. “It has huge advantages in that it does not require constructions for massive infrastructure that costs enormous amount of money such as high-speed rail or urban aviation and with our design, it is minimally affected by weather conditions.” he emphasized.
On a different note, the IAC @ CES 2023 is co-hosted by the Consumer Technology Association (CTA) and Energy Systems Network (ESN), the organizers of CES. Last year’s IAC winner, Technische Universität München of Germany, and MIT-PITT-RW, a team of Massachusetts Institute of Technology (Massachusetts), University of Pittsburgh (Pennsylvania), Rochester Institute of Technology (New York), University of Waterloo (Canada), with and the University of Waterloo, along with TII EuroRacing - University of Modena and Reggio Emilia (Italy), Technology Innovation Institute (United Arab Emirates), and five other teams are in the race for the win against KAIST.
Photo 5. KAIST Team’s vehicle on the track during the IAC @ CES 2022
The Indy Autonomous Challenge is scheduled to hold its fifth competition at the Monza track in Italy in June 2023 and the sixth competition at CES 2024.
2023.01.05 View 8964 -
A New Family of Ducks joins the Feathery KAISTians
In October of this year, KAIST signed an 'Agreement for the Training Program for AI Semiconductor Designers' with Samsung Electronics, to conduct joint research and actively nurture master's and doctorate researchers in the field of Semiconductors designed exclusively for AI devices. To celebrate this commemorative agreement for cooperation bound for mutual success, Samsung Electronics gifted a set of 5 ducks to KAIST.
The Duck Pond and the Geese have been representing KAIST as famous mascots.
It all started back in 2000, when the incumbent President, Professor Kwang Hyung Lee served was then a professor at the Department of Bio and Brain Engineering, he first picked up a pack of ducks from Yuseong Market and started taking care of it on campus around the Carillon pond. While the ducks came and went, eventually being replaced with a pack of geese over the time, for more than 20 years, the pack of feathery KAISTians stole the eyes of the passersby and were loved by both the on-campus members and the visitors, alike.
The representative of the Samsung Electronics said that the pack of ducks comprising of a new breed contains the message of SEC that it hopes that the PIM semiconductor technology will grow to become the super-gap technology that would turn heads and grab attention of the world as the mascot of Korea's technological prowess under the combined care of KAIST and SEC.
Would the ducks find KAIST likable? We will keep you informed of how they are doing!
2022.11.01 View 5132 -
Phage resistant Escherichia coli strains developed to reduce fermentation failure
A genome engineering-based systematic strategy for developing phage resistant Escherichia coli strains has been successfully developed through the collaborative efforts of a team led by Professor Sang Yup Lee, Professor Shi Chen, and Professor Lianrong Wang. This study by Xuan Zou et al. was published in Nature Communications in August 2022 and featured in Nature Communications Editors’ Highlights. The collaboration by the School of Pharmaceutical Sciences at Wuhan University, the First Affiliated Hospital of Shenzhen University, and the KAIST Department of Chemical and Biomolecular Engineering has made an important advance in the metabolic engineering and fermentation industry as it solves a big problem of phage infection causing fermentation failure.
Systems metabolic engineering is a highly interdisciplinary field that has made the development of microbial cell factories to produce various bioproducts including chemicals, fuels, and materials possible in a sustainable and environmentally friendly way, mitigating the impact of worldwide resource depletion and climate change. Escherichia coli is one of the most important chassis microbial strains, given its wide applications in the bio-based production of a diverse range of chemicals and materials. With the development of tools and strategies for systems metabolic engineering using E. coli, a highly optimized and well-characterized cell factory will play a crucial role in converting cheap and readily available raw materials into products of great economic and industrial value.
However, the consistent problem of phage contamination in fermentation imposes a devastating impact on host cells and threatens the productivity of bacterial bioprocesses in biotechnology facilities, which can lead to widespread fermentation failure and immeasurable economic loss. Host-controlled defense systems can be developed into effective genetic engineering solutions to address bacteriophage contamination in industrial-scale fermentation; however, most of the resistance mechanisms only narrowly restrict phages and their effect on phage contamination will be limited.
There have been attempts to develop diverse abilities/systems for environmental adaptation or antiviral defense. The team’s collaborative efforts developed a new type II single-stranded DNA phosphorothioation (Ssp) defense system derived from E. coli 3234/A, which can be used in multiple industrial E. coli strains (e.g., E. coli K-12, B and W) to provide broad protection against various types of dsDNA coliphages. Furthermore, they developed a systematic genome engineering strategy involving the simultaneous genomic integration of the Ssp defense module and mutations in components that are essential to the phage life cycle. This strategy can be used to transform E. coli hosts that are highly susceptible to phage attack into strains with powerful restriction effects on the tested bacteriophages. This endows hosts with strong resistance against a wide spectrum of phage infections without affecting bacterial growth and normal physiological function. More importantly, the resulting engineered phage-resistant strains maintained the capabilities of producing the desired chemicals and recombinant proteins even under high levels of phage cocktail challenge, which provides crucial protection against phage attacks.
This is a major step forward, as it provides a systematic solution for engineering phage-resistant bacterial strains, especially industrial bioproduction strains, to protect cells from a wide range of bacteriophages. Considering the functionality of this engineering strategy with diverse E. coli strains, the strategy reported in this study can be widely extended to other bacterial species and industrial applications, which will be of great interest to researchers in academia and industry alike.
Fig. A schematic model of the systematic strategy for engineering phage-sensitive industrial E. coli strains into strains with broad antiphage activities. Through the simultaneous genomic integration of a DNA phosphorothioation-based Ssp defense module and mutations of components essential for the phage life cycle, the engineered E. coli strains show strong resistance against diverse phages tested and maintain the capabilities of producing example recombinant proteins, even under high levels of phage cocktail challenge.
2022.08.23 View 11711 -
Interactive Map of Metabolical Synthesis of Chemicals
An interactive map that compiled the chemicals produced by biological, chemical and combined reactions has been distributed on the web
- A team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, organized and distributed an all-inclusive listing of chemical substances that can be synthesized using microorganisms
- It is expected to be used by researchers around the world as it enables easy assessment of the synthetic pathway through the web.
A research team comprised of Woo Dae Jang, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported an interactive metabolic map of bio-based chemicals. Their research paper “An interactive metabolic map of bio-based chemicals” was published online in Trends in Biotechnology on August 10, 2022.
As a response to rapid climate change and environmental pollution, research on the production of petrochemical products using microorganisms is receiving attention as a sustainable alternative to existing methods of productions. In order to synthesize various chemical substances, materials, and fuel using microorganisms, it is necessary to first construct the biosynthetic pathway toward desired product by exploration and discovery and introduce them into microorganisms. In addition, in order to efficiently synthesize various chemical substances, it is sometimes necessary to employ chemical methods along with bioengineering methods using microorganisms at the same time. For the production of non-native chemicals, novel pathways are designed by recruiting enzymes from heterologous sources or employing enzymes designed though rational engineering, directed evolution, or ab initio design.
The research team had completed a map of chemicals which compiled all available pathways of biological and/or chemical reactions that lead to the production of various bio-based chemicals back in 2019 and published the map in Nature Catalysis. The map was distributed in the form of a poster to industries and academia so that the synthesis paths of bio-based chemicals could be checked at a glance.
The research team has expanded the bio-based chemicals map this time in the form of an interactive map on the web so that anyone with internet access can quickly explore efficient paths to synthesize desired products. The web-based map provides interactive visual tools to allow interactive visualization, exploration, and analysis of complex networks of biological and/or chemical reactions toward the desired products. In addition, the reported paper also discusses the production of natural compounds that are used for diverse purposes such as food and medicine, which will help designing novel pathways through similar approaches or by exploiting the promiscuity of enzymes described in the map. The published bio-based chemicals map is also available at http://systemsbiotech.co.kr.
The co-first authors, Dr. Woo Dae Jang and Ph.D. student Gi Bae Kim, said, “We conducted this study to address the demand for updating the previously distributed chemicals map and enhancing its versatility.” “The map is expected to be utilized in a variety of research and in efforts to set strategies and prospects for chemical production incorporating bio and chemical methods that are detailed in the map.”
Distinguished Professor Sang Yup Lee said, “The interactive bio-based chemicals map is expected to help design and optimization of the metabolic pathways for the biosynthesis of target chemicals together with the strategies of chemical conversions, serving as a blueprint for developing further ideas on the production of desired chemicals through biological and/or chemical reactions.”
The interactive metabolic map of bio-based chemicals.
2022.08.11 View 12841 -
Metabolically Engineered Bacterium Produces Lutein
A research group at KAIST has engineered a bacterial strain capable of producing lutein. The research team applied systems metabolic engineering strategies, including substrate channeling and electron channeling, to enhance the production of lutein in an engineered Escherichia coli strain. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries.
Figure: Systems metabolic engineering was employed to construct and optimize the metabolic pathways for lutein production, and substrate channeling and electron channeling strategies were additionally employed to increase the production of the lutein with high productivity.
Lutein is classified as a xanthophyll chemical that is abundant in egg yolk, fruits, and vegetables. It protects the eye from oxidative damage from radiation and reduces the risk of eye diseases including macular degeneration and cataracts. Commercialized products featuring lutein are derived from the extracts of the marigold flower, which is known to harbor abundant amounts of lutein. However, the drawback of lutein production from nature is that it takes a long time to grow and harvest marigold flowers. Furthermore, it requires additional physical and chemical-based extractions with a low yield, which makes it economically unfeasible in terms of productivity. The high cost and low yield of these bioprocesses has made it difficult to readily meet the demand for lutein.
These challenges inspired the metabolic engineers at KAIST, including researchers Dr. Seon Young Park, Ph.D. Candidate Hyunmin Eun, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team’s study entitled “Metabolic engineering of Escherichia coli with electron channeling for the production of natural products” was published in Nature Catalysis on August 5, 2022.
This research details the ability to produce lutein from E. coli with a high yield using a cheap carbon source, glycerol, via systems metabolic engineering. The research group focused on solving the bottlenecks of the biosynthetic pathway for lutein production constructed within an individual cell. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, lutein was produced when the lutein biosynthesis pathway was introduced, albeit in very small amounts.
To improve the productivity of lutein production, the bottleneck enzymes within the metabolic pathway were first identified. It turned out that metabolic reactions that involve a promiscuous enzyme, an enzyme that is involved in two or more metabolic reactions, and electron-requiring cytochrome P450 enzymes are the main bottleneck steps of the pathway inhibiting lutein biosynthesis.
To overcome these challenges, substrate channeling, a strategy to artificially recruit enzymes in physical proximity within the cell in order to increase the local concentrations of substrates that can be converted into products, was employed to channel more metabolic flux towards the target chemical while reducing the formation of unwanted byproducts.
Furthermore, electron channeling, a strategy similar to substrate channeling but differing in terms of increasing the local concentrations of electrons required for oxidoreduction reactions mediated by P450 and its reductase partners, was applied to further streamline the metabolic flux towards lutein biosynthesis, which led to the highest titer of lutein production achieved in a bacterial host ever reported. The same electron channeling strategy was successfully applied for the production of other natural products including nootkatone and apigenin in E. coli, showcasing the general applicability of the strategy in the research field.
“It is expected that this microbial cell factory-based production of lutein will be able to replace the current plant extraction-based process,” said Dr. Seon Young Park, the first author of the paper. She explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals.
“As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Sang Yup Lee.
This work was supported by the Cooperative Research Program for Agriculture Science & Technology Development funded by the Rural Development Administration of Korea, with further support from the Development of Next-generation Biorefinery Platform Technologies for Leading Bio-based Chemicals Industry Project and by the Development of Platform Technologies of Microbial Cell Factories for the Next-generation Biorefineries Project of the National Research Foundation funded by the Ministry of Science and ICT of Korea.
2022.08.05 View 9094 -
Atomically-Smooth Gold Crystals Help to Compress Light for Nanophotonic Applications
Highly compressed mid-infrared optical waves in a thin dielectric crystal on monocrystalline gold substrate investigated for the first time using a high-resolution scattering-type scanning near-field optical microscope.
KAIST researchers and their collaborators at home and abroad have successfully demonstrated a new platform for guiding the compressed light waves in very thin van der Waals crystals. Their method to guide the mid-infrared light with minimal loss will provide a breakthrough for the practical applications of ultra-thin dielectric crystals in next-generation optoelectronic devices based on strong light-matter interactions at the nanoscale.
Phonon-polaritons are collective oscillations of ions in polar dielectrics coupled to electromagnetic waves of light, whose electromagnetic field is much more compressed compared to the light wavelength. Recently, it was demonstrated that the phonon-polaritons in thin van der Waals crystals can be compressed even further when the material is placed on top of a highly conductive metal. In such a configuration, charges in the polaritonic crystal are “reflected” in the metal, and their coupling with light results in a new type of polariton waves called the image phonon-polaritons. Highly compressed image modes provide strong light-matter interactions, but are very sensitive to the substrate roughness, which hinders their practical application.
Challenged by these limitations, four research groups combined their efforts to develop a unique experimental platform using advanced fabrication and measurement methods. Their findings were published in Science Advances on July 13.
A KAIST research team led by Professor Min Seok Jang from the School of Electrical Engineering used a highly sensitive scanning near-field optical microscope (SNOM) to directly measure the optical fields of the hyperbolic image phonon-polaritons (HIP) propagating in a 63 nm-thick slab of hexagonal boron nitride (h-BN) on a monocrystalline gold substrate, showing the mid-infrared light waves in dielectric crystal compressed by a hundred times.
Professor Jang and a research professor in his group, Sergey Menabde, successfully obtained direct images of HIP waves propagating for many wavelengths, and detected a signal from the ultra-compressed high-order HIP in a regular h-BN crystals for the first time. They showed that the phonon-polaritons in van der Waals crystals can be significantly more compressed without sacrificing their lifetime.
This became possible due to the atomically-smooth surfaces of the home-grown gold crystals used as a substrate for the h-BN. Practically zero surface scattering and extremely small ohmic loss in gold at mid-infrared frequencies provide a low-loss environment for the HIP propagation. The HIP mode probed by the researchers was 2.4 times more compressed and yet exhibited a similar lifetime compared to the phonon-polaritons with a low-loss dielectric substrate, resulting in a twice higher figure of merit in terms of the normalized propagation length.
The ultra-smooth monocrystalline gold flakes used in the experiment were chemically grown by the team of Professor N. Asger Mortensen from the Center for Nano Optics at the University of Southern Denmark.
Mid-infrared spectrum is particularly important for sensing applications since many important organic molecules have absorption lines in the mid-infrared. However, a large number of molecules is required by the conventional detection methods for successful operation, whereas the ultra-compressed phonon-polariton fields can provide strong light-matter interactions at the microscopic level, thus significantly improving the detection limit down to a single molecule. The long lifetime of the HIP on monocrystalline gold will further improve the detection performance.
Furthermore, the study conducted by Professor Jang and the team demonstrated the striking similarity between the HIP and the image graphene plasmons. Both image modes possess significantly more confined electromagnetic field, yet their lifetime remains unaffected by the shorter polariton wavelength. This observation provides a broader perspective on image polaritons in general, and highlights their superiority in terms of the nanolight waveguiding compared to the conventional low-dimensional polaritons in van der Waals crystals on a dielectric substrate.
Professor Jang said, “Our research demonstrated the advantages of image polaritons, and especially the image phonon-polaritons. These optical modes can be used in the future optoelectronic devices where both the low-loss propagation and the strong light-matter interaction are necessary. I hope that our results will pave the way for the realization of more efficient nanophotonic devices such as metasurfaces, optical switches, sensors, and other applications operating at infrared frequencies.”
This research was funded by the Samsung Research Funding & Incubation Center of Samsung Electronics and the National Research Foundation of Korea (NRF). The Korea Institute of Science and Technology, Ministry of Education, Culture, Sports, Science and Technology of Japan, and The Villum Foundation, Denmark, also supported the work.
Figure. Nano-tip is used for the ultra-high-resolution imaging of the image phonon-polaritons in hBN launched by the gold crystal edge.
Publication:
Menabde, S. G., et al. (2022) Near-field probing of image phonon-polaritons in hexagonal boron nitride on gold crystals. Science Advances 8, Article ID: eabn0627. Available online at https://science.org/doi/10.1126/sciadv.abn0627.
Profile:
Min Seok Jang, MS, PhD
Associate Professor
jang.minseok@kaist.ac.kr
http://janglab.org/
Min Seok Jang Research Group
School of Electrical Engineering
http://kaist.ac.kr/en/
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
2022.07.13 View 11860 -
Team KAIST Makes Its Presence Felt in the Self-Driving Tech Industry
Team KAIST finishes 4th at the inaugural CES Autonomous Racing Competition
Team KAIST led by Professor Hyunchul Shim and Unmanned Systems Research Group (USRG) placed fourth in an autonomous race car competition in Las Vegas last week, making its presence felt in the self-driving automotive tech industry.
Team KAIST, beat its first competitor, Auburn University, with speeds of up to 131 mph at the Autonomous Challenge at CES held at the Las Vegas Motor Speedway. However, the team failed to advance to the final round when it lost to PoliMOVE, comprised of the Polytechnic University of Milan and the University of Alabama, the final winner of the $150,000 USD race.
A total of eight teams competed in the self-driving race. The race was conducted as a single elimination tournament consisting of multiple rounds of matches. Two cars took turns playing the role of defender and attacker, and each car attempted to outpace the other until one of them was unable to complete the mission.
Each team designed the algorithm to control its racecar, the Dallara-built AV-21, which can reach a speed of up to 173 mph, and make it safely drive around the track at high speeds without crashing into the other.
The event is the CES version of the Indy Autonomous Challenge, a competition that took place for the first time in October last year to encourage university students from around the world to develop complicated software for autonomous driving and advance relevant technologies. Team KAIST placed 4th at the Indy Autonomous Challenge, which qualified it to participate in this race.
“The technical level of the CES race is much higher than last October’s and we had a very tough race. We advanced to the semifinals for two consecutive races. I think our autonomous vehicle technology is proving itself to the world,” said Professor Shim.
Professor Shim’s research group has been working on the development of autonomous aerial and ground vehicles for the past 12 years. A self-driving car developed by the lab was certified by the South Korean government to run on public roads.
The vehicle the team used cost more than 1 million USD to build. Many of the other teams had to repair their vehicle more than once due to accidents and had to spend a lot on repairs. “We are the only one who did not have any accidents, and this is a testament to our technological prowess,” said Professor Shim.
He said the financial funding to purchase pricy parts and equipment for the racecar is always a challenge given the very tight research budget and absence of corporate sponsorships.
However, Professor Shim and his research group plan to participate in the next race in September and in the 2023 CES race.
“I think we need more systemic and proactive research and support systems to earn better results but there is nothing better than the group of passionate students who are taking part in this project with us,” Shim added.
2022.01.12 View 9967