bio
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Simulations Open a New Way to Reverse Cell Aging
Turning off a newly identified enzyme could reverse a natural aging process in cells.
Research findings by a KAIST team provide insight into the complex mechanism of cellular senescence and present a potential therapeutic strategy for reducing age-related diseases associated with the accumulation of senescent cells.
Simulations that model molecular interactions have identified an enzyme that could be targeted to reverse a natural aging process called cellular senescence. The findings were validated with laboratory experiments on skin cells and skin equivalent tissues, and published in the Proceedings of the National Academy of Sciences (PNAS).
“Our research opens the door for a new generation that perceives aging as a reversible biological phenomenon,” says Professor Kwang-Hyun Cho of the Department of Bio and Brain engineering at the Korea Advanced Institute of Science and Technology (KAIST), who led the research with colleagues from KAIST and Amorepacific Corporation in Korea.
Cells respond to a variety of factors, such as oxidative stress, DNA damage, and shortening of the telomeres capping the ends of chromosomes, by entering a stable and persistent exit from the cell cycle. This process, called cellular senescence, is important, as it prevents damaged cells from proliferating and turning into cancer cells. But it is also a natural process that contributes to aging and age-related diseases. Recent research has shown that cellular senescence can be reversed. But the laboratory approaches used thus far also impair tissue regeneration or have the potential to trigger malignant transformations.
Professor Cho and his colleagues used an innovative strategy to identify molecules that could be targeted for reversing cellular senescence. The team pooled together information from the literature and databases about the molecular processes involved in cellular senescence. To this, they added results from their own research on the molecular processes involved in the proliferation, quiescence (a non-dividing cell that can re-enter the cell cycle) and senescence of skin fibroblasts, a cell type well known for repairing wounds. Using algorithms, they developed a model that simulates the interactions between these molecules. Their analyses allowed them to predict which molecules could be targeted to reverse cell senescence.
They then investigated one of the molecules, an enzyme called PDK1, in incubated senescent skin fibroblasts and three-dimensional skin equivalent tissue models. They found that blocking PDK1 led to the inhibition of two downstream signalling molecules, which in turn restored the cells’ ability to enter back into the cell cycle. Notably, the cells retained their capacity to regenerate wounded skin without proliferating in a way that could lead to malignant transformation.
The scientists recommend investigations are next done in organs and organisms to determine the full effect of PDK1 inhibition. Since the gene that codes for PDK1 is overexpressed in some cancers, the scientists expect that inhibiting it will have both anti-aging and anti-cancer effects.
-Profile
Professor Kwang-Hyun Cho
Laboratory for Systems Biology and Bio-Inspired Engineering
http://sbie.kaist.ac.kr
Department of Bio and Brain Engineering
KAIST
2020.11.26 View 12949 -
Researchers Control Multiple Wavelengths of Light from a Single Source
KAIST researchers have synthesized a collection of nanoparticles, known as carbon dots, capable of emitting multiple wavelengths of light from a single particle. Additionally, the team discovered that the dispersion of the carbon dots, or the interparticle distance between each dot, influences the properties of the light the carbon dots emit. The discovery will allow researchers to understand how to control these carbon dots and create new, environmentally responsible displays, lighting, and sensing technology.
Research into nanoparticles capable of emitting light, such as quantum dots, has been an active area of interest for the last decade and a half. These particles, or phosphors, are nanoparticles made out of various materials that are capable of emitting light at specific wavelengths by leveraging quantum mechanical properties of the materials. This provides new ways to develop lighting and display solutions as well as more precise detection and sensing in instruments.
As technology becomes smaller and more sophisticated, the usage of fluorescent nanoparticles has seen a dramatic increase in many applications due to the purity of the colors emitting from the dots as well as their tunability to meet desired optical properties.
Carbon dots, a type of fluorescent nanoparticles, have seen an increase in interest from researchers as a candidate to replace non-carbon dots, the construction of which requires heavy metals that are toxic to the environment. Since they are made up of mostly carbon, the low toxicity is an extremely attractive quality when coupled with the tunability of their inherent optical properties.
Another striking feature of carbon dots is their capability to emit multiple wavelengths of light from a single nanoparticle. This multi-wavelength emission can be stimulated under a single excitation source, enabling the simple and robust generation of white light from a single particle by emitting multiple wavelengths simultaneously.
Carbon dots also exhibit a concentration-dependent photoluminescence. In other words, the distance between individual carbon dots affects the light that the carbon dots subsequently emit under an excitation source. These combined properties make carbon dots a unique source that will result in extremely accurate detection and sensing.
This concentration-dependency, however, had not been fully understood. In order to fully utilize the capabilities of carbon dots, the mechanisms that govern the seemingly variable optical properties must first be uncovered. It was previously theorized that the concentration-dependency of carbon dots was due to a hydrogen bonding effect.
Now, a KAIST research team, led by Professor Do Hyun Kim of the Department of Chemical and Biomolecular Engineering has posited and demonstrated that the dual-color-emissiveness is instead due to the interparticle distances between each carbon dot. This study was made available online in June 2020 ahead of final publication in the 36th Issue of Physical Chemistry Chemical Physics on September 28, 2020.
First author of the paper, PhD candidate Hyo Jeong Yoo, along with Professor Kim and researcher Byeong Eun Kwak, examined how the relative light intensity of the red and blue colors changed when varying the interparticle distances, or concentration, of the carbon dots. They found that as the concentration was adjusted, the light emitted from the carbon dots would transform. By varying the concentration, the team was able to control the relative intensity of the colors, as well as emit them simultaneously to generate a white light from a single source (See Figure).
“The concentration-dependence of the photoluminescence of carbon dots on the change of the emissive origins for different interparticle distances has been overlooked in previous research. With the analysis of the dual-color-emission phenomenon of carbon dots, we believe that this result may provide a new perspective to investigate their photoluminescence mechanism,” Yoo explained.
The newly analyzed ability to control the photoluminescence of carbon dots will likely be heavily utilized in the continued development of solid-state lighting applications and sensing.
Publication:
Yoo, H. J., Kwak, B. E., and Kim. D. H. (2020) Interparticle distance as a key factor for controlling the dual-emission properties of carbon dots. Physical Chemistry Chemical Physics, Issue 36, Pages 20227-20237. Available online at https://doi.org/10.1039/d0cp02120b
Profile:
Do Hyun Kim, Sc.D.
Professor
dokim@kaist.ac.kr
http://procal.kaist.ac.kr/
Process Analysis Laboratory
Department of Chemical and Biomolecular Engineering
https://www.kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea
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2020.11.23 View 10832 -
In Memory of Professor Dong-Soo Kim
Pioneering geotechnical engineer Dong-Soo Kim dies at 59
The Department of Civil and Environmental Engineering lost a pioneering scholar in geotechnical engineering, Professor Dong-Soo Kim. Professor Kim died on November 3, after a one-and-a-half-year battle with a brain tumor. He was 59.
Known for his piercing insight and infectious enthusiasm for the deepest questions in geotechnical science and engineering, Professor Kim built an extraordinary academic career while working at KAIST for 26 years. Professor Kim paved the way for establishing the geo-centrifuge experiment facilities at KAIST as part of the KOCED (Korea Construction Engineering Development Collaboratory Management Institute) Projects funded by the Ministry of Land, Infrastructure and Transport. He also served as director of the KOCED Geo-Centrifuge Center.
“He made significant contributions to the growth of the department since his joining and he was at the forefront of the globalization of the department. He passed away so early leaving behind so many projects,” lamented Professor Emeritus Chung-Bang Yun.
“Professor Kim insisted on lecturing despite his serious illness. He wanted to play his part so gracefully for his students until his last days,” said Professor Hyo-Gyong Kwak, the head of the department who was also a close colleague of 25 years. “His captivating warm smile and unwavering mentorship and guidance will be missed by students and faculty alike. We lost an exemplary leader, mentor, colleague, and friend.” One of his colleagues, Professor Gye-Chun Cho said, “We have lost a great professor and colleague in civil engineering worldwide. His impact and legacy will be remembered forever.”
Joining the KAIST faculty in 1994, he began his academic career at the Polytechnique University, New York for three years after earning his PhD at the University of Texas at Austin in 1991. He finished his BS and MS at Seoul National University in 1983 and 1985 respectively.
While at KAIST, he led the Soil Dynamics Lab in 1994 and researched on site characterization via field and lab tests. He also conducted geotechnical centrifuge tests on earthquake and offshore geotechnical problems. His research team studied the seismic design of geotechnical structures and explored the non-destructive testing and evaluation of civil structures.
Professor Kim made profound contributions to understanding fundamental geotechnical engineering problems. More recently, his lab investigated physical modeling using the geo-centrifuge testing machine that could simulate field geotechnical problems on small-scale models. Professor Kim’s perseverance, deep curiosity, and enthusiasm for discovery served him well in his roles as a teacher, mentor, and colleague in the department and beyond. “I thought of him as an elder brother who fully understand everything with generous mind,” said Professor Haeng-Ki Lee, former head of the department.
“I will never forget the hiking trip to Halla Mountain in Jeju last summer. He continuously cheered on the junior professors. Without him, we could not have made it to the summit. His support and encouragement always led us to produce good results and achievement in the labs,” remembered Professor Youngchul Kim. Taking great delight in helping young scientists, he inspired colleagues and students to find their own eureka moments. To professors like Jong-In Han and Ayoung Kim, he was the role model they hope to be due to his rigorous scholarship and generous character. Upon his passing, Professor Jaewook Myung reviewed all the emails he and Professor Kim has sent starting from his undergraduate days at KAIST. “He was my guiding light. He always listened attentively to my struggles from my undergraduate days and advised me very warmly.”
Professor Kim was also known for his key role in the Korean Geotechnical Society. His unmatched leadership led him to serve as the Chair of the Organizing Committee for the 19th International Conference on Soil Mechanics and Geotechnical Engineering in Seoul in 2017. He was the General Secretary of the 5th International Symposium on Deformation Characteristics of Geomaterials. He also served as a chair of the ISSSMGE TC 104 committee.
Professor Kim successfully carried out numerous projects with his research team and supervised more than 60 graduate students. For current students under his supervision, it is still tough to acknowledge the loss of their professor.
Master candidate Yeonjun Kim feels lost moving forward. PhD candidate Junsik Bae said that it is like a bad dream and he feels Professor Kim will still be in his lab whenever he goes inside. One of the staff members who worked with him, Byeol-Nim Cha, remembered that Professor Kim always entered the office with a big smile. “He always asked me how I am doing,” Cha added.
Professor Kim’s trailblazing research was recognized with several awards and honors. Cited as a Top 100 Scientist by the International Biographical Center (IBC) in 2008, Professor Kim received the Young Presidential Research Award from the Korean Academy of Science and Technology in 2002, the Korean Presidential Award on Civil Engineer’s Day in 2011, and the Telford Premium Rewards in 2018. Throughout his career, he authored or co-authored 321 papers in international journals and conference proceedings, and 278 papers in domestic journals and conferences.
President of the Korean Geotechnical Society Choong-gi Chung also eulogized him, “Above his impressive professional contributions, Professor Kim will be remembered forever for his generosity, simplicity, playfulness, and his smile.”
Professor Kim is survived by his wife, son, and daughter.
2020.11.19 View 7946 -
Engineered C. glutamicum Strain Capable of Producing High-Level Glutaric Acid from Glucose
An engineered C. glutamicum strain that can produce the world’s highest titer of glutaric acid was developed by employing systems metabolic engineering strategies
A metabolic engineering research group at KAIST has developed an engineered Corynebacterium glutamicum strain capable of producing high-level glutaric acid without byproducts from glucose. This new strategy will be useful for developing engineered micro-organisms for the bio-based production of value-added chemicals.
Glutaric acid, also known as pentanedioic acid, is a carboxylic acid that is widely used for various applications including the production of polyesters, polyamides, polyurethanes, glutaric anhydride, 1,5-pentanediol, and 5-hydroxyvaleric acid. Glutaric acid has been produced using various petroleum-based chemical methods, relying on non-renewable and toxic starting materials. Thus, various approaches have been taken to biologically produce glutaric acid from renewable resources. Previously, the development of the first glutaric acid producing Escherichia coli by introducing Pseudomonas putida genes was reported by a research group from KAIST, but the titer was low. Glutaric acid production by metabolically engineered Corynebacterium glutamicum has also been reported in several studies, but further improvements in glutaric acid production seemed possible since C. glutamicum has the capability of producing more than 130 g/L of L-lysine.
A research group comprised of Taehee Han, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. Their research paper “Glutaric acid production by systems metabolic engineering of an L-lysine-overproducing Corynebacterium glutamicum” was published online in PNAS on November 16, 2020.
This research reports the development of a metabolically engineered C. glutamicum strain capable of efficiently producing glutaric acid, starting from an L-lysine overproducer. The following novel strategies and approaches to achieve high-level glutaric acid production were employed. First, metabolic pathways in C. glutamicum were reconstituted for glutaric acid production by introducing P. putida genes. Then, multi-omics analyses including genome, transcriptome, and fluxome were conducted to understand the phenotype of the L-lysine overproducer strain. In addition to systematic understanding of the host strain, gene manipulation targets were predicted by omics analyses and applied for engineering C. glutamicum, which resulted in the development of an engineered strain capable of efficiently producing glutaric acid. Furthermore, the new glutaric acid exporter was discovered for the first time, which was used to further increase glutaric acid production through enhancing product excretion. Last but not least, culture conditions were optimized for high-level glutaric acid production. As a result, the final engineered strain was able to produce 105.3 g/L glutaric acid, the highest titer ever reported, in 69 hours by fed-batch fermentation.
Professor Sang Yup Lee said, “It is meaningful that we were able to develop a highly efficient glutaric acid producer capable of producing glutaric acid at the world’s highest titer without any byproducts from renewable carbon sources. This will further accelerate the bio-based production of valuable chemicals in pharmaceutical/medical/chemical industries.” This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation and funded by the Ministry of Science and ICT.
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
2020.11.17 View 7392 -
KAIST Showcases Healthcare Technologies at K-Hospital Fair 2020
KAIST Pavilion showcased its innovative medical and healthcare technologies and their advanced applications at the K-Hospital Fair 2020. Five KAIST research groups who teamed up for the Post-COVID-19 New Deal R&D Initiative Project participated in the fair held in Seoul last week.
The K-Hospital Fair is a yearly event organized by the Korean Hospital Association to present the latest research and practical innovations to help the medical industry better serve the patients. This year, 120 healthcare organizations participated in the fair and operated 320 booths.
At the fair, a research group led by Professor Il-Doo Kim from the Department of Materials Science and Engineering demonstrated the manufacturing process of orthogonal nanofibers used to develop their ‘recyclable nano-fiber filtered face mask’ introduced in March of this year. This mask has garnered immense international attention for maintaining its sturdy frame and filtering function even after being washed more than 20 times. Professor Kim is now extending his facilities for the mass production of this mask at his start-up company. While awaiting final approval from the Ministry of Food and Drug Safety to bring his product into the market, Professor Kim is developing other mask variations such as eco-friendly biodegradable masks and transparent masks to aid the hearing-impaired who rely on lip reading to communicate.
The team working under Professor Wonho Choe from the Department of Nuclear and Quantum Engineering presented two low-temperature plasma sterilizers for medical use, co-developed with Plasmapp, a start-up company founded by a KAIST alumnus. Their sterilizers are the first ones that can sterilize medical devices by diffusing hydrogen peroxide vapor into the pouch. They rapidly sterilize medical instruments and materials in just seven minutes without leaving toxic residue, while reducing sterilization time and costs by 90%.
Professor Hyung-Soon Park and his researchers from the Department of Mechanical Engineering introduced a smart protective suit ventilation system that features high cooling capacity and a slimmed-down design. For comfortable use, the suit is equipped with a technique that monitors its inner temperature and humidity and automatically controls its inner circulation accordingly. The group also presented a new system that helps a person in a contaminated suit undress without coming into contact with the contaminated outer part of the suit.
Professor Jong Chul Ye's group from the Department of Bio and Brain Engineering demonstrated AI software that can quickly diagnose an infectious disease based on chest X-ray imaging. The technique compares the differences in the severity of pneumonia in individual patients to distinguish whether their conditions fall under viral pneumonia including COVID-19, bacterial pneumonia, tuberculosis, other diseases, or normal conditions. The AI software visualizes the basis of its reasoning for each of the suspected diseases and provides them as information that can be utilized by medical personnel.
Finally, researchers of Professor Ki-Hun Jeong’s team from the Department of Bio and Brain Engineering demonstrated their ultra-high-speed sub-miniature molecular diagnostic system for the on-site diagnosis of diseases. The existing Polymerase Chain Reaction (PCR) diagnostic usually takes from 30 minutes to an hour to provide results, but their new technique using an LED light source can present results within just three minutes and it is expected to be used actively for on-site diagnosis.
Professor Choongsik Bae, the Director of the Post-COVID-19 New Deal R&D Initiative Project, said, “KAIST will build a healthy relationship amongst researchers, enterprises, and hospitals to contribute to the end of COVID-19 and build a new paradigm of Korean disease prevention and control.”
KAIST launched the Post-COVID-19 New Deal R&D Initiative in July with the support of the Ministry of Science and ICT of Korea. This unit was created to overcome the pandemic crisis by using science and technology, and to contribute to economic development by creating a new antiviral drug industry. The unit is comprised of 464 KAIST members including professors, researchers, and students as well as 503 professionals from enterprises, hospitals, and research centers.
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2020.10.26 View 14289 -
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 13241 -
Big Ideas on Emerging Materials Explored at EMS
Renowned scholars and editors from academic journals joined the Emerging Materials e-Symposium (EMS) held at KAIST and shared the latest breakthroughs and big ideas in new material development last month. This e-symposium was organized by Professor Il-Doo Kim from the KAIST Department of Materials Sciences and Engineering over five days from September 21 through 25 via Zoom and YouTube. Professor Kim also serves as an associate editor of ACS Nano.
Esteemed scholars and editors of academic journals including ACS Nano, Nano Energy, and Energy Storage Materials made Zoom presentations in three main categories: 1) nanostructures for next-generation applications, 2) chemistry and biotechnology for applications in the fields of environment and industry, and 3) material innovation for technological applications.
During Session I, speakers including Professor John A. Rogers of Northwestern University and Professor Zhenan Bao of Stanford University led the session on Emerging Soft Electronics and 3D printing.
In later sessions, other globally recognized scholars gave talks titled Advanced Nanostructuring for Emerging Materials, Frontiers in Emerging Materials Research, Advanced Energy Materials and Functional Nanomaterials, and Latest Advances in Nanomaterials Research.
These included 2010 Nobel Prize laureate and professor at Manchester University Andre Geim, editor-in-chief of ACS Nano and professor at UCLA Paul S. Weiss, Professor Paul Alivisatos of UC Berkeley, Professor William Chueh of Stanford University, and Professor Mircea Dinca of MIT.
KAIST President Sung-Chul Shin, who is also a materials physicist, said in his opening address, “Innovation in materials science will become an important driving force to change our way of life. All the breakthroughs in materials have extended a new paradigm that has transformed our lives.”
“Creative research projects alongside global collaborators like all of you will allow the breakthroughs that will deliver us from these crises,” he added.
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2020.10.06 View 15066 -
E. coli Engineered to Grow on CO₂ and Formic Acid as Sole Carbon Sources
- An E. coli strain that can grow to a relatively high cell density solely on CO₂ and formic acid was developed by employing metabolic engineering. -
Most biorefinery processes have relied on the use of biomass as a raw material for the production of chemicals and materials. Even though the use of CO₂ as a carbon source in biorefineries is desirable, it has not been possible to make common microbial strains such as E. coli grow on CO₂.
Now, a metabolic engineering research group at KAIST has developed a strategy to grow an E. coli strain to higher cell density solely on CO₂ and formic acid. Formic acid is a one carbon carboxylic acid, and can be easily produced from CO₂ using a variety of methods. Since it is easier to store and transport than CO₂, formic acid can be considered a good liquid-form alternative of CO₂.
With support from the C1 Gas Refinery R&D Center and the Ministry of Science and ICT, a research team led by Distinguished Professor Sang Yup Lee stepped up their work to develop an engineered E. coli strain capable of growing up to 11-fold higher cell density than those previously reported, using CO₂ and formic acid as sole carbon sources. This work was published in Nature Microbiology on September 28.
Despite the recent reports by several research groups on the development of E. coli strains capable of growing on CO₂ and formic acid, the maximum cell growth remained too low (optical density of around 1) and thus the production of chemicals from CO₂ and formic acid has been far from realized.
The team previously reported the reconstruction of the tetrahydrofolate cycle and reverse glycine cleavage pathway to construct an engineered E. coli strain that can sustain growth on CO₂ and formic acid. To further enhance the growth, the research team introduced the previously designed synthetic CO₂ and formic acid assimilation pathway, and two formate dehydrogenases.
Metabolic fluxes were also fine-tuned, the gluconeogenic flux enhanced, and the levels of cytochrome bo3 and bd-I ubiquinol oxidase for ATP generation were optimized. This engineered E. coli strain was able to grow to a relatively high OD600 of 7~11, showing promise as a platform strain growing solely on CO₂ and formic acid.
Professor Lee said, “We engineered E. coli that can grow to a higher cell density only using CO₂ and formic acid. We think that this is an important step forward, but this is not the end. The engineered strain we developed still needs further engineering so that it can grow faster to a much higher density.”
Professor Lee’s team is continuing to develop such a strain. “In the future, we would be delighted to see the production of chemicals from an engineered E. coli strain using CO₂ and formic acid as sole carbon sources,” he added.
-Profile:Distinguished Professor Sang Yup Leehttp://mbel.kaist.ac.krDepartment of Chemical and Biomolecular EngineeringKAIST
2020.09.29 View 11378 -
Deep Learning Helps Explore the Structural and Strategic Bases of Autism
Psychiatrists typically diagnose autism spectrum disorders (ASD) by observing a person’s behavior and by leaning on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), widely considered the “bible” of mental health diagnosis.
However, there are substantial differences amongst individuals on the spectrum and a great deal remains unknown by science about the causes of autism, or even what autism is. As a result, an accurate diagnosis of ASD and a prognosis prediction for patients can be extremely difficult.
But what if artificial intelligence (AI) could help? Deep learning, a type of AI, deploys artificial neural networks based on the human brain to recognize patterns in a way that is akin to, and in some cases can surpass, human ability. The technique, or rather suite of techniques, has enjoyed remarkable success in recent years in fields as diverse as voice recognition, translation, autonomous vehicles, and drug discovery.
A group of researchers from KAIST in collaboration with the Yonsei University College of Medicine has applied these deep learning techniques to autism diagnosis. Their findings were published on August 14 in the journal IEEE Access.
Magnetic resonance imaging (MRI) scans of brains of people known to have autism have been used by researchers and clinicians to try to identify structures of the brain they believed were associated with ASD. These researchers have achieved considerable success in identifying abnormal grey and white matter volume and irregularities in cerebral cortex activation and connections as being associated with the condition.
These findings have subsequently been deployed in studies attempting more consistent diagnoses of patients than has been achieved via psychiatrist observations during counseling sessions. While such studies have reported high levels of diagnostic accuracy, the number of participants in these studies has been small, often under 50, and diagnostic performance drops markedly when applied to large sample sizes or on datasets that include people from a wide variety of populations and locations.
“There was something as to what defines autism that human researchers and clinicians must have been overlooking,” said Keun-Ah Cheon, one of the two corresponding authors and a professor in Department of Child and Adolescent Psychiatry at Severance Hospital of the Yonsei University College of Medicine.
“And humans poring over thousands of MRI scans won’t be able to pick up on what we’ve been missing,” she continued. “But we thought AI might be able to.”
So the team applied five different categories of deep learning models to an open-source dataset of more than 1,000 MRI scans from the Autism Brain Imaging Data Exchange (ABIDE) initiative, which has collected brain imaging data from laboratories around the world, and to a smaller, but higher-resolution MRI image dataset (84 images) taken from the Child Psychiatric Clinic at Severance Hospital, Yonsei University College of Medicine. In both cases, the researchers used both structural MRIs (examining the anatomy of the brain) and functional MRIs (examining brain activity in different regions).
The models allowed the team to explore the structural bases of ASD brain region by brain region, focusing in particular on many structures below the cerebral cortex, including the basal ganglia, which are involved in motor function (movement) as well as learning and memory.
Crucially, these specific types of deep learning models also offered up possible explanations of how the AI had come up with its rationale for these findings.
“Understanding the way that the AI has classified these brain structures and dynamics is extremely important,” said Sang Wan Lee, the other corresponding author and an associate professor at KAIST. “It’s no good if a doctor can tell a patient that the computer says they have autism, but not be able to say why the computer knows that.”
The deep learning models were also able to describe how much a particular aspect contributed to ASD, an analysis tool that can assist psychiatric physicians during the diagnosis process to identify the severity of the autism.
“Doctors should be able to use this to offer a personalized diagnosis for patients, including a prognosis of how the condition could develop,” Lee said.
“Artificial intelligence is not going to put psychiatrists out of a job,” he explained. “But using AI as a tool should enable doctors to better understand and diagnose complex disorders than they could do on their own.”
-ProfileProfessor Sang Wan LeeDepartment of Bio and Brain EngineeringLaboratory for Brain and Machine Intelligence https://aibrain.kaist.ac.kr/
KAIST
2020.09.23 View 11380 -
Biomarker Predicts Who Will Have Severe COVID-19
- Airway cell analyses showing an activated immune axis could pinpoint the COVID-19 patients who will most benefit from targeted therapies.-
KAIST researchers have identified key markers that could help pinpoint patients who are bound to get a severe reaction to COVID-19 infection. This would help doctors provide the right treatments at the right time, potentially saving lives. The findings were published in the journal Frontiers in Immunology on August 28.
People’s immune systems react differently to infection with SARS-CoV-2, the virus that causes COVID-19, ranging from mild to severe, life-threatening responses.
To understand the differences in responses, Professor Heung Kyu Lee and PhD candidate Jang Hyun Park from the Graduate School of Medical Science and Engineering at KAIST analysed ribonucleic acid (RNA) sequencing data extracted from individual airway cells of healthy controls and of mildly and severely ill patients with COVID-19. The data was available in a public database previously published by a group of Chinese researchers.
“Our analyses identified an association between immune cells called neutrophils and special cell receptors that bind to the steroid hormone glucocorticoid,” Professor Lee explained. “This finding could be used as a biomarker for predicting disease severity in patients and thus selecting a targeted therapy that can help treat them at an appropriate time,” he added.
Severe illness in COVID-19 is associated with an exaggerated immune response that leads to excessive airway-damaging inflammation. This condition, known as acute respiratory distress syndrome (ARDS), accounts for 70% of deaths in fatal COVID-19 infections.
Scientists already know that this excessive inflammation involves heightened neutrophil recruitment to the airways, but the detailed mechanisms of this reaction are still unclear.
Lee and Park’s analyses found that a group of immune cells called myeloid cells produced excess amounts of neutrophil-recruiting chemicals in severely ill patients, including a cytokine called tumour necrosis factor (TNF) and a chemokine called CXCL8.
Further RNA analyses of neutrophils in severely ill patients showed they were less able to recruit very important T cells needed for attacking the virus. At the same time, the neutrophils produced too many extracellular molecules that normally trap pathogens, but damage airway cells when produced in excess.
The researchers additionally found that the airway cells in severely ill patients were not expressing enough glucocorticoid receptors. This was correlated with increased CXCL8 expression and neutrophil recruitment.
Glucocorticoids, like the well-known drug dexamethasone, are anti-inflammatory agents that could play a role in treating COVID-19. However, using them in early or mild forms of the infection could suppress the necessary immune reactions to combat the virus. But if airway damage has already happened in more severe cases, glucocorticoid treatment would be ineffective.
Knowing who to give this treatment to and when is really important. COVID-19 patients showing reduced glucocorticoid receptor expression, increased CXCL8 expression, and excess neutrophil recruitment to the airways could benefit from treatment with glucocorticoids to prevent airway damage. Further research is needed, however, to confirm the relationship between glucocorticoids and neutrophil inflammation at the protein level.
“Our study could serve as a springboard towards more accurate and reliable COVID-19 treatments,” Professor Lee said.
This work was supported by the National Research Foundation of Korea, and Mobile Clinic Module Project funded by KAIST.
Figure. Low glucocorticoid receptor (GR) expression led to excessive inflammation and lung damage by neutrophils through enhancing the expression of CXCL8 and other cytokines.
Image credit: Professor Heung Kyu Lee, KAIST. Created with Biorender.com.
Image usage restrictions: News organizations may use or redistribute these figures and image, with proper attribution, as part of news coverage of this paper only.
-Publication:
Jang Hyun Park, and Heung Kyu Lee. (2020). Re-analysis of Single Cell Transcriptome Reveals That the NR3C1-CXCL8-Neutrophil Axis Determines the Severity of COVID-19. Frontiers in Immunology, Available online at https://doi.org/10.3389/fimmu.2020.02145
-Profile: Heung Kyu Lee
Associate Professor
heungkyu.lee@kaist.ac.kr
https://www.heungkyulee.kaist.ac.kr/
Laboratory of Host Defenses
Graduate School of Medical Science and Engineering (GSMSE)
The Center for Epidemic Preparedness at KAIST Institute
http://kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile: Jang Hyun Park
PhD Candidate
janghyun.park@kaist.ac.kr
GSMSE, KAIST
2020.09.17 View 16096 -
Life After COVID-19: Big Questions on Medical and Bio-Engineering
KAIST GSI forum explores big questions in the medical and bio-engineering revolution caused by the COVID-19 in fight against infectious diseases and life quality
On September 9, the Global Strategy Institute at KAIST will delve into innovative future strategies for the medical and bio-engineering sectors that have been disrupted by COVID-19. The forum will live stream via YouTube, KTV, and Naver TV from 9:00 am Korean time.
The online forum features a speaker lineup of world-renowned scholars who will discuss an array of bio-engineering technologies that will improve our quality of life and even extend our life span. This is the GSI’s third online forum since the first one in April that covered the socio-economic implications of the global pandemic and the second one in June focusing on the education sector.
In hosting the third round of the GSI Forum series, KAIST President Sung-Chul Shin stressed the power of science and technology saying, “In this world full of uncertainties, one thing for sure is that only the advancement of science and technology will deliver us from this crisis.” Korean Prime Minister Sye-Kyun Chung will also deliver a speech explaining the government’s response to COVID-19 and vaccine development strategies.
The President of the National Academy of Medicine in the US will share ideal policies to back up the bio-engineering and medical sectors and Futurist Thomas Frey from the Davinci Institute will present his distinct perspectives on our future lives after COVID-19. His thought-provoking insights on advancements in the bioengineering sector will examine whether humanity can put an end to infectious diseases and find new ways to lengthen our lives.
Two distinguished professors in the field of genetic engineering technology will share their latest breakthroughs. Professor George McDonald Church from Harvard Medical School who developed genome sequencing will deliver a keynote speech on how the advancement of gene editing and genome technology will overcome diseases and contribute to extending human life spans.
Professor Kwang-Soo Kim, a KAIST alumnus from Harvard Medical School who recently reported new discoveries for Parkinson’s disease treatment by reprogramming a patient’s own skin cells to replace cells in the brain, will introduce the latest clinical cell treatment technologies based on personalized therapeutics.
Senior Vice President and Chief Product Officer of Illumina Susan Tousi, a leading genome sequencing solution provider, will describe genome analysis technology and explore the potential for disease prevention.
KAIST medical scientist Jeong Ho Lee, who was the first to identify the causes of intractable epilepsies and has identified the genes responsible for several developmental brain disorders. Professor Jin-Hyung Lee from Stanford University and Dr. David B. Resnik from the National Institute of Environmental Health Science will also join the speaker lineup to discuss genetics-based personalized solutions to extend human life spans.
The forum will also invite about 50 young scientists and medical researchers from around the world to participate in an online panel session. They will engage in a Q&A session and a discussion with the speakers.
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2020.09.04 View 10511 -
Virtual Commencement Ceremony Honors the Class of 2020
The KAIST community gathered online to celebrate the 2020 graduating class. The blended ceremony conferred their hard-earned degrees on August 28. The belated celebration, which was postponed from February 21 due to the COVID-19 outbreak, honored the 2846 graduates with live streaming on YouTube beginning at 2:00 pm. The graduates include 721 PhDs and 1399 master’s degree holders.
The government raised its social distancing guidelines to level two out of three on August 23 as the second wave of the virus hit the nation. Level two guidelines prohibit the gathering of more than 50 persons indoors or 100 persons outdoors.
For the virtual ceremony, the Office of Student Affairs and Policy announced a list of 67 graduates who signed up to participate in the graduation ceremony. Graduates were divided into three groups to attend at three different places and watch the ceremony via Zoom. No family and friends of the graduates were allowed to participate at the campus.
This year’s valedictorian, Kon-Yong Lee from the Department of Chemical and Biomolecular Engineering, received the Award of Minister of Science and Technology. Salutorian Hee-Kwang Roh from the Department of Chemistry received the Award of the KAIST Board of Trustees, while the recipient of the KAIST Presidential Award was Hong Jae-Min from the School of Computing.
President Sung-Chul Shin, Chairman of the Board of Trustees Woo-Sik Kim, former Minister of Science and Technology and former Provost at KAIST Dr. KunMo Chung, and a very limited number of faculty and staff members officiated the commencement ceremony from the KAIST auditorium.
President Shin in his commencement speech applauded the graduates’ hard work and dedication and delivered a very special congratulatory message to them. He encouraged the new graduates to be courageous enough to deal with these new challenges as well as future uncertainties, during the greatest transformation brought about by COVID-19.
“Instead of following behind others as a fast follower, we should take the initiative and walk down new paths as a first mover.” He also stressed, “We can transform this crisis into an opportunity by practicing the C3 values KAIST pursues: Challenging, Creating, and Caring.”
As new alumni of Korea’s top science and technology university, he said, “Our graduates should focus on creating the world’s best, first, or only one in their research or their work.” However, he also pointed out the importance of a caring mind for others when working together.
At the ceremony, KAIST conferred an honorary doctorate degree to Dr. Younghoon David Kim, CEO and Chairman of Daesung Group, in recognition of his lifetime dedication to making innovations in the energy industry.
Daesung Group is a leading energy company in Korea which manufactures and supplies natural gas for industries and home users. Dr. Kim is committed to making efficient energy sources by advancing cutting-energy sciences and disruptive technologies. He has served as chairman of the World Energy Council since 2016.
In his acceptance speech, Kim stressed the Grand Energy Transition as a new driving force in the future energy industry for maximizing energy efficiency.
“Since energy is the most basic foundation for all industries, improvements in energy efficiency translate into benefits for all related industries in terms of its efficiency and productivity.”
“The Grand Energy Transition is progressing widely and rapidly across the entire value chain of energy production, distribution, and consumption with decarbonization, decentralization, and digitalization serving as its driving force.”
He went on, “We should regard energy efficiency not as the fifth fuel but the first primary fuel.”
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2020.08.28 View 11530