Ro
-
A Study Reveals What Triggers Lung Damage during COVID-19
A longitudinal study of macrophages from SARS-CoV-2 infected lungs offers new insights into dynamic immunological changes
A KAIST immunology research team found that a specific subtype of macrophages that originated from blood monocytes plays a key role in the hyper-inflammatory response in SARS-CoV-2 infected lungs, by performing single-cell RNA sequencing of bronchoalveolar lavage fluid cells. This study provides new insights for understanding dynamic changes in immune responses to COVID-19.
In the early phase of COVID-19, SARS-CoV-2 infected lung tissue and the immediate defense system is activated. This early and fast response is called ‘innate immunity,’ provided by immune cells residing in lungs. Macrophages are major cell types of the innate immune system of the lungs, and newly differentiated macrophages originating from the bloodstream also contribute to early defenses against viruses.
Professor Su-Hyung Park and his collaborators investigated the quantitative and qualitative evaluation of immune responses in the lungs of SARS-CoV-2 infected ferrets. To overcome the limitations of research using patient-originated specimens, the researchers used a ferret infection model to obtain SARS-CoV-2 infected lungs sequentially with a defined time interval.
The researchers analyzed the 10 subtypes of macrophages during the five-day course of SARS-CoV-2 infection, and found that infiltrating macrophages originating from activated monocytes in the blood were key players for viral clearance as well as damaged lung tissue. Moreover, they found that the differentiation process of these inflammatory macrophages resembled the immune responses in the lung tissue of severe COVID-19 patients.
Currently, the research team is conducting a follow-up study to identify the dynamic changes in immune responses during the use of immunosuppressive agents to control hyper-inflammatory response called ‘cytokine storm’ in patients with COVID-19.
Dr. Jeong Seok Lee, the chief medical officer at Genome Insight Inc., explained, “Our analysis will enhance the understanding of the early features of COVID-19 immunity and provide a scientific background for the more precise use of immunosuppressive agents targeting specific macrophage subtypes.”
“This study is the first longitudinal study using sequentially obtained immune cells originating from SARS-CoV-2 infected lungs. The research describes the innate immune response to COVID-19 using single cell transcriptome data and enhances our understanding of the two phases of inflammatory responses,” Professor Park said.
This work was supported by the Ministry of Health and Welfare and KAIST, and was published in Nature Communications on July 28.
-PublicationSu-Hyung Park, Jeong Seok Lee, Su-Hyung Park et al. “Single-cell transcriptome of bronchoalverolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets” Nature Communications (https://doi.org/10.1038/s41467-021-24807-0)
-ProfileProfessor Su-Hyung ParkLaboratory of Translational Immunology and Vaccinologyhttps://ltiv.kaist.ac.kr/
Graduate School of Medical Science and EngineeringKAIST
2021.08.04 View 14457 -
KPC4IR Helping to Create Global Standards for Virtual Transactions
KPC4IR will join the task force for the Global Implementation of Travel Rule Standards
The KAIST Policy Center for the Fourth Industrial Revolution (KPC4IR) will participate in a global initiative to create global standards for virtual asset transactions. As a member of the GI-TRUST (Global Implementation of Travel Rule Standards) task force, the KPC4IR will develop technical standards and relevant policies that support the global implementation of the travel rule for virtual assets in compliance with the recommendations of the Financial Action Task Force’s (FATF).
The FATF is an intergovernmental organization founded in 1989 by the G7 to develop policies to combat money laundering. In June 2019, the FATF extended its Recommendation 16, commonly known as the “travel rule,” to virtual asset services providers (VASPs), requiring both financial institutions and VASPs to aggregate information on the senders and recipients of wire transfers and exchange this information between parties to create a suitable audit trail.
According to the FATF’s recommendation and the G20’s support, jurisdictions, especially G20 member countries, have now applied the travel rule to their respective local laws. Korea also amended the Act on Reporting and Using Specified Financial Transaction Information in March 2020 to include virtual assets in their regulatory scope by March 2022.
The GI-TRUST task force will collaborate with global and local organizations developing travel rule technologies and offer a neutral assessment of proposed solutions. Their activities are aimed at standardizing related authentication protocols and security technologies that help VASPs comply with the travel rule.
The task force will also aid in the pilot testing of travel rule solutions for certain VASPs in Korea. Afterwards, the task force will report on the performance and reliability of the tested travel rule solutions for actual virtual asset transactions, in compliance with the FATF’s guidance.
Besides the KPC4IR, the GI-TRUST task force includes the Global Blockchain Business Council (GBBC), International Digital Asset Exchange Association (IDAXA), and Korea Blockchain Association (KBCA).
Director of the KPC4IR Professor So Young Kim will co-chair the task force. Professor Kim said their approach should be prudential in dealing with the regulations that rely on secure real-name data on top of the opposing governance style of pseudonymization, distribution, and recombination.
She explained, “KAIST has designed the co-evolution of technologies and institutions in conjunction with the global leaders’ groups such as the World Economic Forum and the EC Joint Research Center.”
She expects KAIST’s interdisciplinary, global cooperation to untie the entangled problem between regulations and technologies that obstruct future pathways.
2021.07.30 View 10478 -
3D Visualization and Quantification of Bioplastic PHA in a Living Bacterial Cell
3D holographic microscopy leads to in-depth analysis of bacterial cells accumulating the bacterial bioplastic, polyhydroxyalkanoate (PHA)
A research team at KAIST has observed how bioplastic granule is being accumulated in living bacteria cells through 3D holographic microscopy. Their 3D imaging and quantitative analysis of the bioplastic ‘polyhydroxyalkanoate’ (PHA) via optical diffraction tomography provides insights into biosynthesizing sustainable substitutes for petroleum-based plastics.
The bio-degradable polyester polyhydroxyalkanoate (PHA) is being touted as an eco-friendly bioplastic to replace existing synthetic plastics. While carrying similar properties to general-purpose plastics such as polyethylene and polypropylene, PHA can be used in various industrial applications such as container packaging and disposable products.
PHA is synthesized by numerous bacteria as an energy and carbon storage material under unbalanced growth conditions in the presence of excess carbon sources. PHA exists in the form of insoluble granules in the cytoplasm. Previous studies on investigating in vivo PHA granules have been performed by using fluorescence microscopy, transmission electron microscopy (TEM), and electron cryotomography.
These techniques have generally relied on the statistical analysis of multiple 2D snapshots of fixed cells or the short-time monitoring of the cells. For the TEM analysis, cells need to be fixed and sectioned, and thus the investigation of living cells was not possible. Fluorescence-based techniques require fluorescence labeling or dye staining. Thus, indirect imaging with the use of reporter proteins cannot show the native state of PHAs or cells, and invasive exogenous dyes can affect the physiology and viability of the cells. Therefore, it was difficult to fully understand the formation of PHA granules in cells due to the technical limitations, and thus several mechanism models based on the observations have been only proposed.
The team of metabolic engineering researchers led by Distinguished Professor Sang Yup Lee and Physics Professor YongKeun Park, who established the startup Tomocube with his 3D holographic microscopy, reported the results of 3D quantitative label-free analysis of PHA granules in individual live bacterial cells by measuring the refractive index distributions using optical diffraction tomography. The formation and growth of PHA granules in the cells of Cupriavidus necator, the most-studied native PHA (specifically, poly(3-hydroxybutyrate), also known as PHB) producer, and recombinant Escherichia coli harboring C. necator PHB biosynthesis pathway were comparatively examined.
From the reconstructed 3D refractive index distribution of the cells, the team succeeded in the 3D visualization and quantitative analysis of cells and intracellular PHA granules at a single-cell level. In particular, the team newly presented the concept of “in vivo PHA granule density.” Through the statistical analysis of hundreds of single cells accumulating PHA granules, the distinctive differences of density and localization of PHA granules in the two micro-organisms were found. Furthermore, the team identified the key protein that plays a major role in making the difference that enabled the characteristics of PHA granules in the recombinant E. coli to become similar to those of C. necator.
The research team also presented 3D time-lapse movies showing the actual processes of PHA granule formation combined with cell growth and division. Movies showing the living cells synthesizing and accumulating PHA granules in their native state had never been reported before.
Professor Lee said, “This study provides insights into the morphological and physical characteristics of in vivo PHA as well as the unique mechanisms of PHA granule formation that undergo the phase transition from soluble monomers into the insoluble polymer, followed by granule formation. Through this study, a deeper understanding of PHA granule formation within the bacterial cells is now possible, which has great significance in that a convergence study of biology and physics was achieved. This study will help develop various bioplastics production processes in the future.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (Grants NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) and the Bio & Medical Technology Development Program (Grant No. 2021M3A9I4022740) from the Ministry of Science and ICT (MSIT) through the National Research Foundation (NRF) of Korea to S.Y.L. This work was also supported by the KAIST Cross-Generation Collaborative Laboratory project.
-PublicationSo Young Choi, Jeonghun Oh, JaeHwang Jung, YongKeun Park, and Sang Yup Lee. Three-dimensional label-free visualization and quantification of polyhydroxyalkanoates in individualbacterial cell in its native state. PNAS(https://doi.org./10.1073/pnas.2103956118)
-ProfileDistinguished Professor Sang Yup LeeMetabolic Engineering and Synthetic Biologyhttp://mbel.kaist.ac.kr/
Department of Chemical and Biomolecular Engineering KAIST
Endowed Chair Professor YongKeun ParkBiomedical Optics Laboratoryhttps://bmokaist.wordpress.com/
Department of PhysicsKAIST
2021.07.28 View 15989 -
Prof. Changho Suh Named the 2021 James L. Massey Awardee
Professor Changho Suh from the School of Electrical Engineering was named the recipient of the 2021 James L.Massey Award. The award recognizes outstanding achievement in research and teaching by young scholars in the information theory community. The award is named in honor of James L. Massey, who was an internationally acclaimed pioneer in digital communications and revered teacher and mentor to communications engineers.
Professor Suh is a recipient of numerous awards, including the 2021 James L. Massey Research & Teaching Award for Young Scholars from the IEEE Information Theory Society, the 2019 AFOSR Grant, the 2019 Google Education Grant, the 2018 IEIE/IEEE Joint Award, the 2015 IEIE Haedong Young Engineer Award, the 2013 IEEE Communications Society Stephen O. Rice Prize, the 2011 David J. Sakrison Memorial Prize (the best dissertation award in UC Berkeley EECS), the 2009 IEEE ISIT Best Student Paper Award, the 2020 LINKGENESIS Best Teacher Award (the campus-wide Grand Prize in Teaching), and the four Departmental Teaching Awards (2013, 2019, 2020, 2021).
Dr. Suh is an IEEE Information Theory Society Distinguished Lecturer, the General Chair of the Inaugural IEEE East Asian School of Information Theory, and a Member of the Young Korean Academy of Science and Technology. He is also an Associate Editor of Machine Learning for the IEEE Transactions on Information Theory, the Editor for the IEEE Information Theory Newsletter, a Column Editor for IEEE BITS the Information Theory Magazine, an Area Chair of NeurIPS 2021, and on the Senior Program Committee of IJCAI 2019–2021.
2021.07.27 View 9947 -
Prof. Junil Choi Receives the Neal Shepherd Memorial Award
Professor Junil Choi of the School of Electrical Engineering received the 2021 Neal Shepherd Memorial Award from the IEEE Vehicular Technology Society. The award recognizes the most outstanding paper relating to radio propagation published in major journals over the previous five years.
Professor Cho, the recipient of the 2015 IEEE Signal Processing Society’s and the 2019 IEEE Communications Society’s Best Paper Award, was selected as the awardee for his paper titled “The Impact of Beamwidth on Temporal Channel Variation in Vehicular Channels and Its Implications” in IEEE Transaction on Vehicular Technology in 2017.
In this paper, Professor Choi and his team derived the channel coherence time for a wireless channel as a function of the beamwidth, taking both Doppler effect and pointing error into consideration. The results showed that a nonzero optimal beamwidth exists that maximizes the channel coherence time. To reduce the impact of the overhead of doing realignment in every channel coherence time, the paper showed that the beams should be realigned every beam coherence time for the best performance.
Professor Choi said, “It is quite an honor to receive this prestigious award following Professor Joonhyun Kang who won the IEEE VTS’s Jack Neubauer Memorial Award this year. It shows that our university’s pursuit of excellence in advanced research is being well recognized.”
2021.07.26 View 8211 -
VP Sang Yup Lee Honored with the Pony Chung Innovation Award
Vice President for Research Sang Yup Lee became the recipient of the Innovation Award by the Pony Chung Foundation that was established to honor the late Se-yung Chung, the former chairman of Hyundai Development Company. He will receive 200 million KRW in prize money. Chairman Chung developed Korea’s first domestically manufactured automobile, ‘Pony,’ in the mid-1970s that became the cornerstone of Korea’s auto industry today.
Distinguished Professor Lee, from the Department of Chemical and Biomolecular Engineering, is a pioneering scholar in the field of systems metabolic engineering who developed various micro-organisms for producing a wide range of fuels, chemicals, materials, and natural compounds.
He recently was elected as a foreign member of the Royal Society in the UK and is the first Korean ever elected into the National Academy of Inventors (NAI) in the US as well as one of 13 scholars elected as an International Member of both the National Academy of Sciences (NAS) and the National Academy of Engineering (NAE) in the US.
2021.07.13 View 12431 -
Professor Jung Receives the Hansong Science Award
Professor Yousung Jung of the Department of Chemical and Biomolecular Engineering has been selected as the recipient of the 5th Hansong Science Award in Chemistry. The award recognizes young and mid-career scholars who made outstanding achievement in physics, chemistry, and life sciences. Recipients receive 50 million KRW in prize money.
Professor Jung was recognized for finding a new way to predict synthesis potentials when designing data-based materials and molecules through AI-powered inverse technology. Conventionally, new material discovery mainly relied on a method where the new materials were proposed by an expert’s intuition or experimental trial, then synthesized to measure the properties of the material before it was used. However, this method took a lot of time, which resulted in an inefficient discovery process.
Professor Jung’s AI reverse design technology is reported to be more efficient for discovering new materials by finding crystal structures with desired properties using data and AI algorithms.
"AI reverse design technology can accelerate the development of new materials and new drugs," Professor Jung said. "It can be used as an algorithm for future autonomous laboratories implemented by robots, algorithms, and data without human intervention," he added.
2021.07.13 View 8807 -
Hydrogel-Based Flexible Brain-Machine Interface
The interface is easy to insert into the body when dry, but behaves ‘stealthily’ inside the brain when wet
Professor Seongjun Park’s research team and collaborators revealed a newly developed hydrogel-based flexible brain-machine interface. To study the structure of the brain or to identify and treat neurological diseases, it is crucial to develop an interface that can stimulate the brain and detect its signals in real time. However, existing neural interfaces are mechanically and chemically different from real brain tissue. This causes foreign body response and forms an insulating layer (glial scar) around the interface, which shortens its lifespan.
To solve this problem, the research team developed a ‘brain-mimicking interface’ by inserting a custom-made multifunctional fiber bundle into the hydrogel body. The device is composed not only of an optical fiber that controls specific nerve cells with light in order to perform optogenetic procedures, but it also has an electrode bundle to read brain signals and a microfluidic channel to deliver drugs to the brain.
The interface is easy to insert into the body when dry, as hydrogels become solid. But once in the body, the hydrogel will quickly absorb body fluids and resemble the properties of its surrounding tissues, thereby minimizing foreign body response.
The research team applied the device on animal models, and showed that it was possible to detect neural signals for up to six months, which is far beyond what had been previously recorded. It was also possible to conduct long-term optogenetic and behavioral experiments on freely moving mice with a significant reduction in foreign body responses such as glial and immunological activation compared to existing devices.
“This research is significant in that it was the first to utilize a hydrogel as part of a multifunctional neural interface probe, which increased its lifespan dramatically,” said Professor Park. “With our discovery, we look forward to advancements in research on neurological disorders like Alzheimer’s or Parkinson’s disease that require long-term observation.”
The research was published in Nature Communications on June 8, 2021. (Title: Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity) The study was conducted jointly with an MIT research team composed of Professor Polina Anikeeva, Professor Xuanhe Zhao, and Dr. Hyunwoo Yook.
This research was supported by the National Research Foundation (NRF) grant for emerging research, Korea Medical Device Development Fund, KK-JRC Smart Project, KAIST Global Initiative Program, and Post-AI Project.
-PublicationPark, S., Yuk, H., Zhao, R. et al. Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity. Nat Commun 12, 3435 (2021). https://doi.org/10.1038/s41467-021-23802-9
-ProfileProfessor Seongjun ParkBio and Neural Interfaces LaboratoryDepartment of Bio and Brain EngineeringKAIST
2021.07.13 View 13607 -
Professor Kang’s Team Receives the IEEE Jack Newbauer Memorial Award
Professor Joonhyuk Kang of the School of Electrical Engineering received the IEEE Vehicular Technology Society’s 2021 Jack Neubauer Memorial Award for his team’s paper published in IEEE Transactions on Vehicular Technology. The Jack Neubauer Memorial Award recognizes the best paper published in the IEEE Transactions on Vehicular Technology journal in the last five years.
The team of authors, Professor Kang, Professor Sung-Ah Chung at Kyungpook National University, and Professor Osvaldo Simeone of King's College London reported their research titled Mobile Edge Computing via a UAV-Mounted Cloudlet: Optimization of Bit Allocation and Path Planning in IEEE Transactions on Vehicular Technology, Vol. 67, No. 3, pp. 2049-2063, in March 2018.
Their paper shows how the trajectory of aircraft is optimized and resources are allocated when unmanned aerial vehicles perform edge computing to help mobile device calculations. This paper has currently recorded nearly 400 citations (based on Google Scholar). "We are very happy to see the results of proposing edge computing using unmanned aerial vehicles by applying optimization theory, and conducting research on trajectory and resource utilization of unmanned aerial vehicles that minimize power consumption," said Professor Kang.
2021.07.12 View 9655 -
Professor Heung-Sun Sim the MSIT Scientist of July
Professor Heung-Sun Sim from the Department of Physics was selected as the Scientist of July by the Ministry of Science and ICT. Professor Sim was recognized for his research of the Kondo effect, which opened a novel way to engineer spin screening and entanglement by directly observing a quantum phenomenon known as a Kondo screening cloud. His research revealed that the cloud can mediate interactions between distant spins confined in quantum dots, which is a necessary protocol for semiconductor spin-based quantum information processing. This phenomenon is essentially a cloud that masks magnetic impurities in a material. It was known to exist but its spatial extension had never been observed, creating controversy over whether such an extension actually existed. The research was reported in Nature in March 2020. With this award, Professor Sim received 10 million KRW in prize money.
2021.07.12 View 9261 -
Repurposed Drugs Present New Strategy for Treating COVID-19
Virtual screening of 6,218 drugs and cell-based assays identifies best therapeutic medication candidates
A joint research group from KAIST and Institut Pasteur Korea has identified repurposed drugs for COVID-19 treatment through virtual screening and cell-based assays. The research team suggested the strategy for virtual screening with greatly reduced false positives by incorporating pre-docking filtering based on shape similarity and post-docking filtering based on interaction similarity. This strategy will help develop therapeutic medications for COVID-19 and other antiviral diseases more rapidly. This study was reported at the Proceedings of the National Academy of Sciences of the United States of America (PNAS).
Researchers screened 6,218 drugs from a collection of FDA-approved drugs or those under clinical trial and identified 38 potential repurposed drugs for COVID-19 with this strategy. Among them, seven compounds inhibited SARS-CoV-2 replication in Vero cells. Three of these drugs, emodin, omipalisib, and tipifarnib, showed anti-SARS-CoV-2 activity in human lung cells, Calu-3.
Drug repurposing is a practical strategy for developing antiviral drugs in a short period of time, especially during a global pandemic. In many instances, drug repurposing starts with the virtual screening of approved drugs. However, the actual hit rate of virtual screening is low and most of the predicted drug candidates are false positives.
The research group developed effective filtering algorithms before and after the docking simulations to improve the hit rates. In the pre-docking filtering process, compounds with similar shapes to the known active compounds for each target protein were selected and used for docking simulations. In the post-docking filtering process, the chemicals identified through their docking simulations were evaluated considering the docking energy and the similarity of the protein-ligand interactions with the known active compounds.
The experimental results showed that the virtual screening strategy reached a high hit rate of 18.4%, leading to the identification of seven potential drugs out of the 38 drugs initially selected.
“We plan to conduct further preclinical trials for optimizing drug concentrations as one of the three candidates didn’t resolve the toxicity issues in preclinical trials,” said Woo Dae Jang, one of the researchers from KAIST.
“The most important part of this research is that we developed a platform technology that can rapidly identify novel compounds for COVID-19 treatment. If we use this technology, we will be able to quickly respond to new infectious diseases as well as variants of the coronavirus,” said Distinguished Professor Sang Yup Lee.
This work was supported by the KAIST Mobile Clinic Module Project funded by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF). The National Culture Collection for Pathogens in Korea provided the SARS-CoV-2 (NCCP43326).
-PublicationWoo Dae Jang, Sangeun Jeon, Seungtaek Kim, and Sang Yup Lee. Drugs repurposed for COVID-19 by virtual screening of 6,218 drugs and cell-based assay. Proc. Natl. Acad. Sci. U.S.A. (https://doi/org/10.1073/pnas.2024302118)
-ProfileDistinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr
Department of Chemical and Biomolecular EngineeringKAIST
2021.07.08 View 16535 -
Quantum Laser Turns Energy Loss into Gain
A new laser that generates quantum particles can recycle lost energy for highly efficient, low threshold laser applications
Scientists at KAIST have fabricated a laser system that generates highly interactive quantum particles at room temperature. Their findings, published in the journal Nature Photonics, could lead to a single microcavity laser system that requires lower threshold energy as its energy loss increases.
The system, developed by KAIST physicist Yong-Hoon Cho and colleagues, involves shining light through a single hexagonal-shaped microcavity treated with a loss-modulated silicon nitride substrate. The system design leads to the generation of a polariton laser at room temperature, which is exciting because this usually requires cryogenic temperatures.
The researchers found another unique and counter-intuitive feature of this design. Normally, energy is lost during laser operation. But in this system, as energy loss increased, the amount of energy needed to induce lasing decreased. Exploiting this phenomenon could lead to the development of high efficiency, low threshold lasers for future quantum optical devices.
“This system applies a concept of quantum physics known as parity-time reversal symmetry,” explains Professor Cho. “This is an important platform that allows energy loss to be used as gain. It can be used to reduce laser threshold energy for classical optical devices and sensors, as well as quantum devices and controlling the direction of light.”
The key is the design and materials. The hexagonal microcavity divides light particles into two different modes: one that passes through the upward-facing triangle of the hexagon and another that passes through its downward-facing triangle. Both modes of light particles have the same energy and path but don’t interact with each other.
However, the light particles do interact with other particles called excitons, provided by the hexagonal microcavity, which is made of semiconductors. This interaction leads to the generation of new quantum particles called polaritons that then interact with each other to generate the polariton laser. By controlling the degree of loss between the microcavity and the semiconductor substrate, an intriguing phenomenon arises, with the threshold energy becoming smaller as energy loss increases. This research was supported by the Samsung Science and Technology Foundation and Korea’s National Research Foundation.
-PublicationSong,H.G, Choi, M, Woo, K.Y. Yong-Hoon Cho Room-temperature polaritonic non-Hermitian system with single microcavityNature Photonics (https://doi.org/10.1038/s41566-021-00820-z)
-ProfileProfessor Yong-Hoon ChoQuantum & Nanobio Photonics Laboratoryhttp://qnp.kaist.ac.kr/
Department of PhysicsKAIST
2021.07.07 View 12132