Young+Seok+Ju
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'Mini-Lungs' Reveal Early Stages of SARS-CoV-2 Infection
Researchers in Korea and the UK have successfully grown miniature models of critical lung structures called alveoli, and used them to study how the coronavirus that causes COVID-19 infects the lungs.
To date, there have been more than 40 million cases of COVID-19 and almost 1.13 million deaths worldwide. The main target tissues of SARS-CoV-2, the virus that causes COVID-19, especially in patients that develop pneumonia, appear to be alveoli – tiny air sacs in the lungs that take up the oxygen we breathe and exchange it with carbon dioxide to exhale.
To better understand how SARS-CoV-2 infects the lungs and causes disease, a team of Professor Young Seok Ju from the Graduate School of Medical Science and Engineering at KAIST in collaboration with the Wellcome-MRC Cambridge Stem Cell Institute at the University of Cambridge turned to organoids – ‘mini-organs’ grown in three dimensions to mimic the behaviour of tissue and organs.
The team used tissue donated to tissue banks at the Royal Papworth Hospital NHS Foundation Trust and Addenbrooke’s Hospital, Cambridge University NHS Foundations Trust, UK, and Seoul National University Hospital to extract a type of lung cell known as human lung alveolar type 2 cells. By reprogramming these cells back to their earlier ‘stem cell’ stage, they were able to grow self-organizing alveolar-like 3D structures that mimic the behaviour of key lung tissue.
“The research community now has a powerful new platform to study precisely how the virus infects the lungs, as well as explore possible treatments,” said Professor Ju, co-senior author of the research.
Dr. Joo-Hyeon Lee, another co-senior author at the Wellcome-MRC Cambridge Stem Cell Institute, said: “We still know surprisingly little about how SARS-CoV-2 infects the lungs and causes disease. Our approach has allowed us to grow 3D models of key lung tissue – in a sense, ‘mini-lungs’ – in the lab and study what happens when they become infected.”
The team infected the organoids with a strain of SARS-CoV-2 taken from a patient in Korea who was diagnosed with COVID-19 on January 26 after traveling to Wuhan, China. Using a combination of fluorescence imaging and single cell genetic analysis, they were able to study how the cells responded to the virus.
When the 3D models were exposed to SARS-CoV-2, the virus began to replicate rapidly, reaching full cellular infection just six hours after infection. Replication enables the virus to spread throughout the body, infecting other cells and tissue.
Around the same time, the cells began to produce interferons – proteins that act as warning signals to neighbouring cells, telling them to activate their antiviral defences. After 48 hours, the interferons triggered the innate immune response – its first line of defence – and the cells started fighting back against infection.
Sixty hours after infection, a subset of alveolar cells began to disintegrate, leading to cell death and damage to the lung tissue.
Although the researchers observed changes to the lung cells within three days of infection, clinical symptoms of COVID-19 rarely occur so quickly and can sometimes take more than ten days after exposure to appear. The team say there are several possible reasons for this. It may take several days from the virus first infiltrating the upper respiratory tract to it reaching the alveoli. It may also require a substantial proportion of alveolar cells to be infected or for further interactions with immune cells resulting in inflammation before a patient displays symptoms.
“Based on our model we can tackle many unanswered key questions, such as understanding genetic susceptibility to SARS-CoV-2, assessing relative infectivity of viral mutants, and revealing the damage processes of the virus in human alveolar cells,” said Professor Ju. “Most importantly, it provides the opportunity to develop and screen potential therapeutic agents against SARS-CoV-2 infection.”
“We hope to use our technique to grow these 3D models from cells of patients who are particularly vulnerable to infection, such as the elderly or people with diseased lungs, and find out what happens to their tissue,” added Dr. Lee.
The research was a collaboration involving scientists from KAIST, the University of Cambridge, Korea National Institute of Health, Institute for Basic Science (IBS), Seoul National University Hospital and Genome Insight in Korea.
- ProfileProfessor Young Seok JuLaboratory of Cancer Genomics https://julab.kaist.ac.kr the Graduate School of Medical Science and EngineeringKAIST
2020.10.26 View 9840 -
Professor Won-Ki Cho Selected as the 2020 SUHF Young Investigator
Professor Won-Ki Cho from the Department of Biological Sciences was named one of three recipients of the 2020 Suh Kyung-Bae Science Foundation (SUHF) Young Investigator Award.
The SUHF is a non-profit organization established in 2016 and funded by a personal donation of 300 billion KRW in shares from Chairman and CEO Kyung-Bae Suh of the Amorepacific Group. The primary purpose of the foundation is to serve as a platform to nurture and provide comprehensive long-term support for creative and passionate young Korean scientists committed to pursuing research in the field of life sciences. The SUHF selects three to five scientists through an open recruiting process every year and grants each scientist a maximum of 2.5 billion KRW over a period of up to five years.
Since January this year, the foundation received 67 research proposals from scientists across the nation, especially from those who had less than five years of experience as professors, and selected the three recipients.
Professor Cho proposed research on how to observe the interactions between nuclear structures and constantly-changing chromatin monomers in four dimensions through ultra-high-resolution imaging of single living cells. This proposal was recognized as one that could help us better understand the process of transcription regulation, which remains a long-standing question in biology.
The other awards were given to Professor Soung-hun Roh of Seoul National University and Professor Joo-Hyeon Lee of the University of Cambridge.
With these three new awardees, a total of 17 scientists have been named SUHF Young Investigators to date, and the funding to support these scientists now totals 42.5 billion KRW.
Professor Inkyung Jung and Professor Ki-Jun Yoon from the Department of Biological Sciences, and Professor Young Seok Ju and Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering are the four previous winners from KAIST in the years 2017 through 2019.
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2020.10.15 View 10926 -
KAIST Professors Selected as Y-KAST Members
Professor YongKeun Park, Professor Bumjoon Kim, Professor Keon Jae Lee, and Professor Young Seok Ju were selected as the newest members of the Young Korean Academy of Science and Technology (Y-KAST).
The Korean Academy of Science and Technology, an academic institution of professional experts, selected 26 promising scientists under the age of 43 to join Y-KAST. and four KAIST professors were included in the list.
The newest members were conferred on February 26.
Research Field
Name
Natural Sciences
YongKeun Park (Dept. of Physics)
Engineering
Bumjoon Kim (Dept. of Chemical and Biomolecular Engineering)
Agricultural & Fishery Sciences
Keon Jae Lee (Dept. of Materials Science and Engineering)
Medical Sciences
Young Seok Ju (Graduate School of Medical Science and Engineering)
2018.03.05 View 7903