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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
Universal Virus Detection Platform to Expedite Viral Diagnosis
Reactive polymer-based tester pre-screens dsRNAs of a wide range of viruses without their genome sequences The prompt, precise, and massive detection of a virus is the key to combat infectious diseases such as Covid-19. A new viral diagnostic strategy using reactive polymer-grafted, double-stranded RNAs will serve as a pre-screening tester for a wide range of viruses with enhanced sensitivity. Currently, the most widely using viral detection methodology is polymerase chain reaction (PCR) diagnosis, which amplifies and detects a piece of the viral genome. Prior knowledge of the relevant primer nucleic acids of the virus is quintessential for this test. The detection platform developed by KAIST researchers identifies viral activities without amplifying specific nucleic acid targets. The research team, co-led by Professor Sheng Li and Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering, constructed a universal virus detection platform by utilizing the distinct features of the PPFPA-grafted surface and double-stranded RNAs. The key principle of this platform is utilizing the distinct feature of reactive polymer-grafted surfaces, which serve as a versatile platform for the immobilization of functional molecules. These activated surfaces can be used in a wide range of applications including separation, delivery, and detection. As long double-stranded RNAs are common byproducts of viral transcription and replication, these PPFPA-grafted surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences. “We employed the PPFPA-grafted silicon surface to develop a universal virus detection platform by immobilizing antibodies that recognize double-stranded RNAs,” said Professor Kim. To increase detection sensitivity, the research team devised two-step detection process analogues to sandwich enzyme-linked immunosorbent assay where the bound double-stranded RNAs are then visualized using fluorophore-tagged antibodies that also recognize the RNAs’ double-stranded secondary structure. By utilizing the developed platform, long double-stranded RNAs can be detected and visualized from an RNA mixture as well as from total cell lysates, which contain a mixture of various abundant contaminants such as DNAs and proteins. The research team successfully detected elevated levels of hepatitis C and A viruses with this tool. “This new technology allows us to take on virus detection from a new perspective. By targeting a common biomarker, viral double-stranded RNAs, we can develop a pre-screening platform that can quickly differentiate infected populations from non-infected ones,” said Professor Li. “This detection platform provides new perspectives for diagnosing infectious diseases. This will provide fast and accurate diagnoses for an infected population and prevent the influx of massive outbreaks,” said Professor Kim. This work is featured in Biomacromolecules. This work was supported by the Agency for Defense Development (Grant UD170039ID), the Ministry of Science and ICT (NRF-2017R1D1A1B03034660, NRF-2019R1C1C1006672), and the KAIST Future Systems Healthcare Project from the Ministry of Science and ICT (KAISTHEALTHCARE42). Profile:-Professor Yoosik KimDepartment of Chemical and Biomolecular Engineeringhttps://qcbio.kaist.ac.kr KAIST-Professor Sheng LiDepartment of Chemical and Biomolecular Engineeringhttps://bcpolymer.kaist.ac.kr KAIST Publication:Ku et al., 2020. Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity. Biomacromolecules (https://doi.org/10.1021/acs.biomac.0c00379).
Liver Damage Mechanism of Hepatitis C Proven
KAIST researchers found mechanics behind a Hepatitis C virus, thereby taking a step closer to the development of a cure for Hepatitis C. Professor Choi Chul Hui (Department of Biological and Brain Engineering) and Professor Shin Eui Chul (Graduate School of Medical Sciences) proved, for the first time in the world, the mechanism behind liver damage of a patient with Hepatitis C. It is anticipated that this discovery will allow for the development of a Hepatitis C cure that has no side effects and little Liver damage. Hepatitis C is an immune response of the body to the Hepatitis C virus and causes liver irritation. Around 170million people are infected with Hepatitis C worldwide including 1% of the Korean population. Once infected, most cases turn into chronic cases and may lead to liver cancer. However it was impossible to infect Hepatitis C within a test tube cell environment until 2005 and up till then Chimpanzees were used to study the virus which proved to be a huge barrier to research. The research team used cells infected with Hepatitis C virus and found out that the virus works by increasing the destruction of cells by the TNF-a protein responsible for the cell’s immune response. In addition the protein structure of the virus that causes this reaction was successfully found. Conventionally the Hepatitis C medication focused on the suppressing the growth of the virus and therefore had many side effects. The experimental results allow new medication aimed at suppressing the actual mechanism of liver damage to be discovered. The result was selected as the cover dissertation of the September Edition of the Hepatolog magazine.
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