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Genomic Data Reveals New Insights into Human Embryonic Development
KAIST researchers have used whole-genome sequencing to track the development from a single fertilized-egg to a human body
Genomic scientists at KAIST have revealed new insights into the process of human embryonic development using large-scale, whole-genome sequencing of cells and tissues from adult humans. The study, published in Nature on Aug.25, is the first to analyse somatic mutations in normal tissue across multiple organs within and between humans.
An adult human body comprises trillions of cells of more than 200 types. How a human develops from a single fertilized egg to a fully grown adult is a fundamental question in biomedical science. Due to the ethical challenges of performing studies on human embryos, however, the details of this process remain largely unknown.
To overcome these issues, the research team took a different approach. They analysed genetic mutations in cells taken from adult human post-mortem tissue. Specifically, they identified mutations that occur spontaneously in early developmental cell divisions. These mutations, also called genomic scars, act like unique genetic fingerprints that can be used to trace the embryonic development process.
The study, which looked at 334 single-cell colonies and 379 tissue samples from seven recently deceased human body donors, is the largest single-cell, whole-genome analysis carried out to date. The researchers examined the genomic scars of each individual in order to reconstruct their early embryonic cellular dynamics.
The result revealed several key characteristics of the human embryonic development process. Firstly, mutation rates are higher in the first cell division, but then decrease to approximately one mutation per cell during later cell division. Secondly, early cells contributed unequally to the development of the embryo in all informative donors, for example, at the two-cell stage, one of the cells always left more progeny cells than the other. The ratio of this was different from person to person, implying that the process varies between individuals and is not fully deterministic.
The researchers were also able to deduce the timing of when cells begin to differentiate into individual organ-specific cells. They found that within three days of fertilization, embryonic cells began to be distributed asymmetrically into tissues for the left and right sides of the body, followed by differentiation into three germ layers, and then differentiation into specific tissues and organs.
“It is an impressive scientific achievement that, within 20 years of the completion of human genome project, genomic technology has advanced to the extent that we are now able to accurately identify mutations in a single-cell genome,” said Professor Young Seok Ju from the Graduate School of Medical Science and Engineering at KAIST. “This technology will enable us to track human embryogenesis at even higher resolutions in the future.”
The techniques used in this study could be used to improve our understanding of rare diseases caused by abnormalities in embryonic development, and to design new precision diagnostics and treatments for patients.
The research was completed in collaboration with Kyungpook National University Hospital, the Korea Institute of Science and Technology Information, Catholic University of Korea School of Medicine, Genome Insights Inc, and Immune Square Inc. This work was supported by the Suh Kyungbae Foundation, the Ministry of Health and Welfare of Korea, the National Research Foundastion of Korea.
-PublicationSeongyeol Park, Nanda Mali, Ryul Kim et al. ‘Clonal dynamics in early human embryogenesis inferred from somatic mutation’ Nature Online ahead of print, Aug. 25, 2021 (https://doi.org/10.1038/s41586-021-03786-8)
-ProfileProfessor Young Seok JuLab of Cancer Genomics (https://www.julab.kaist.ac.kr/)Graduate School of Medical Science and EngineeringKAIST
2021.08.31 View 10124 -
KAIST KPC4IR Presents the AI Global Guide for Healthcare
The benchmark for the responsible usage of AI technology in the healthcare sector will promote clarity and high standards for technological applications
The KAIST Korea Policy Center for the Fourth Industrial Revolution (KPC4IR) published 'Using AI to Support Healthcare Decisions: A Guide for Society.' This global guide is designed to serve as a benchmark for the responsible usage of AI technologies, and will promote clarity and high standards for technological applications in the healthcare sector. The guide details what should be considered when making clinical decisions to help reduce the chances of the AI giving false or misleading results.
The KPC4IR presented the guide in collaboration with the Lloyd’s Register Foundation Institute for the Public Understanding of Risk at the National University of Singapore (NUS IPUR) and Sense about Science, a non-profit organization in the UK specialized in science communication, during the 2021 SIG-KDD (Special Interest Group on Knowledge Discovery and Data Mining) Conference on August 15.
AI technology is being widely used in the healthcare sector and has already proved its accuracy and efficiency in diagnosing and predicting diseases. Despite its huge impact on our daily lives in every sector of society, AI technology has some drawbacks and comes with risks, especially due to biased algorithms.
“We focused on the ‘reliability’ of AI applications in the healthcare sector to make all data well represented, in good quality. The technology will eventually innovate to better serve the people’s new demand, especially critical demands for safety and precision in healthcare services. This global guide will help both developers and people’s understanding of the appropriate technology applications,” says Director So Young Kim at the KPC4IR.
The guide, for instance, says that to scrutinize quality and reliability, the source of the data must be clearly known; the data must have been collected or selected for the purpose it’s being used for; the limitations and assumptions for that purpose have been clearly stated; the biases have been addressed; and it has been properly tested in the real world. It also reflects the importance of the representativeness of data that will affect the accuracy of the AI applications.
“By being transparent and demonstrating the steps taken to check that the AI is reliable, researchers and developers can help give people confidence about providing their data,” the guide states.
For this guide, the KPC4IR and its collaborators collected data after working with numerous experts from the Graduate School of AI at KAIST, the Science and Technology Policy Institute in Korea, Asan Medical Center in Seoul, Seoul National University Bundang Hospital, and AI solution companies.
2021.08.17 View 9355 -
Brain-Inspired Highly Scalable Neuromorphic Hardware Presented
Neurons and synapses based on single transistor can dramatically reduce the hardware cost and accelerate the commercialization of neuromorphic hardware
KAIST researchers fabricated a brain-inspired highly scalable neuromorphic hardware by co-integrating single transistor neurons and synapses. Using standard silicon complementary metal-oxide-semiconductor (CMOS) technology, the neuromorphic hardware is expected to reduce chip cost and simplify fabrication procedures.
The research team led by Yang-Kyu Choi and Sung-Yool Choi produced a neurons and synapses based on single transistor for highly scalable neuromorphic hardware and showed the ability to recognize text and face images. This research was featured in Science Advances on August 4.
Neuromorphic hardware has attracted a great deal of attention because of its artificial intelligence functions, but consuming ultra-low power of less than 20 watts by mimicking the human brain. To make neuromorphic hardware work, a neuron that generates a spike when integrating a certain signal, and a synapse remembering the connection between two neurons are necessary, just like the biological brain. However, since neurons and synapses constructed on digital or analog circuits occupy a large space, there is a limit in terms of hardware efficiency and costs. Since the human brain consists of about 1011 neurons and 1014 synapses, it is necessary to improve the hardware cost in order to apply it to mobile and IoT devices.
To solve the problem, the research team mimicked the behavior of biological neurons and synapses with a single transistor, and co-integrated them onto an 8-inch wafer. The manufactured neuromorphic transistors have the same structure as the transistors for memory and logic that are currently mass-produced. In addition, the neuromorphic transistors proved for the first time that they can be implemented with a ‘Janus structure’ that functions as both neuron and synapse, just like coins have heads and tails.
Professor Yang-Kyu Choi said that this work can dramatically reduce the hardware cost by replacing the neurons and synapses that were based on complex digital and analog circuits with a single transistor. "We have demonstrated that neurons and synapses can be implemented using a single transistor," said Joon-Kyu Han, the first author. "By co-integrating single transistor neurons and synapses on the same wafer using a standard CMOS process, the hardware cost of the neuromorphic hardware has been improved, which will accelerate the commercialization of neuromorphic hardware,” Han added.This research was supported by the National Research Foundation (NRF) and IC Design Education Center (IDEC).
-PublicationJoon-Kyu Han, Sung-Yool Choi, Yang-Kyu Choi, et al.“Cointegration of single-transistor neurons and synapses by nanoscale CMOS fabrication for highly scalable neuromorphic hardware,” Science Advances (DOI: 10.1126/sciadv.abg8836)
-ProfileProfessor Yang-Kyu ChoiNano-Oriented Bio-Electronics Labhttps://sites.google.com/view/nobelab/
School of Electrical EngineeringKAIST
Professor Sung-Yool ChoiMolecular and Nano Device Laboratoryhttps://www.mndl.kaist.ac.kr/
School of Electrical EngineeringKAIST
2021.08.05 View 12333 -
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 13891 -
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 15084 -
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 7738 -
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 8226 -
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 12902 -
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 9077 -
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 8688 -
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 15656 -
Study of T Cells from COVID-19 Convalescents Guides Vaccine Strategies
Researchers confirm that most COVID-19 patients in their convalescent stage carry stem cell-like memory T cells for months
A KAIST immunology research team found that most convalescent patients of COVID-19 develop and maintain T cell memory for over 10 months regardless of the severity of their symptoms. In addition, memory T cells proliferate rapidly after encountering their cognate antigen and accomplish their multifunctional roles. This study provides new insights for effective vaccine strategies against COVID-19, considering the self-renewal capacity and multipotency of memory T cells.
COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. When patients recover from COVID-19, SARS-CoV-2-specific adaptive immune memory is developed. The adaptive immune system consists of two principal components: B cells that produce antibodies and T cells that eliminate infected cells. The current results suggest that the protective immune function of memory T cells will be implemented upon re-exposure to SARS-CoV-2.
Recently, the role of memory T cells against SARS-CoV-2 has been gaining attention as neutralizing antibodies wane after recovery. Although memory T cells cannot prevent the infection itself, they play a central role in preventing the severe progression of COVID-19. However, the longevity and functional maintenance of SARS-CoV-2-specific memory T cells remain unknown.
Professor Eui-Cheol Shin and his collaborators investigated the characteristics and functions of stem cell-like memory T cells, which are expected to play a crucial role in long-term immunity. Researchers analyzed the generation of stem cell-like memory T cells and multi-cytokine producing polyfunctional memory T cells, using cutting-edge immunological techniques.
This research is significant in that revealing the long-term immunity of COVID-19 convalescent patients provides an indicator regarding the long-term persistence of T cell immunity, one of the main goals of future vaccine development, as well as evaluating the long-term efficacy of currently available COVID-19 vaccines.
The research team is presently conducting a follow-up study to identify the memory T cell formation and functional characteristics of those who received COVID-19 vaccines, and to understand the immunological effect of COVID-19 vaccines by comparing the characteristics of memory T cells from vaccinated individuals with those of COVID-19 convalescent patients.
PhD candidate Jae Hyung Jung and Dr. Min-Seok Rha, a clinical fellow at Yonsei Severance Hospital, who led the study together explained, “Our analysis will enhance the understanding of COVID-19 immunity and establish an index for COVID-19 vaccine-induced memory T cells.”
“This study is the world’s longest longitudinal study on differentiation and functions of memory T cells among COVID-19 convalescent patients. The research on the temporal dynamics of immune responses has laid the groundwork for building a strategy for next-generation vaccine development,” Professor Shin added. This work was supported by the Samsung Science and Technology Foundation and KAIST, and was published in Nature Communications on June 30.
-Publication:
Jung, J.H., Rha, MS., Sa, M. et al. SARS-CoV-2-specific T cell memory is sustained in COVID-19 convalescent patients for 10 months with successful development of stem cell-like memory T cells. Nat Communications 12, 4043 (2021). https://doi.org/10.1038/s41467-021-24377-1
-Profile:
Professor Eui-Cheol Shin
Laboratory of Immunology & Infectious Diseases (http://liid.kaist.ac.kr/)
Graduate School of Medical Science and Engineering
KAIST
2021.07.05 View 14875