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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 10361
Alumni Professor Cho at NYU Endows Scholarship for Female Computer Scientists Alumni Professor Kyunghyun Cho at New York University endowed the “Lim Mi-Sook Scholarship” at KAIST for female computer scientists in honor of his mother. Professor Cho, a graduate of the School of Computing in 2011 completed his master’s and PhD at Alto University in Finland in 2014. He has been teaching at NYU since 2015 and received the Samsung Ho-Am Prize for Engineering this year in recognition of his outstanding researches in the fields of machine learning and AI. “I hope this will encourage young female students to continue their studies in computer science and encourage others to join the discipline in the future, thereby contributing to building a more diverse community of computer scientists,” he said in his written message. His parents and President Kwang Hyung Lee attended the donation ceremony held at the Daejeon campus on June 24. Professor Cho has developed neural network machine learning translation algorithm that is widely being used in translation engines. His contributions to AI-powered translations and innovation in the industry led him to win one of the most prestigious prizes in Korea. He decided to donate his 300 million KRW prize money to fund two 100 million KRW scholarships named after each of his parents: the Lim Mi-Sook Scholarship is for female computer scientists and the Bae-Gyu Scholarly Award for Classics is in honor of his father, who is a Korean literature professor at Soongsil University in Korea. He will also fund a scholarship at Alto University. “I recall there were less than five female students out of 70 students in my cohort during my undergraduate studies at KAIST even in later 2000s. Back then, it just felt natural that boys majored computer science and girls in biology.” He said he wanted to acknowledge his mother, who had to give up her teaching career in the 1980s to take care of her children. “It made all of us think more about the burden of raising children that is placed often disproportionately on mothers and how it should be better distributed among parents, relatives, and society in order to ensure and maximize equity in education as well as career development and advances.” He added, “As a small step to help build a more diverse environment, I have decided to donate to this fund to provide a small supplement to the small group of female students majoring in computer science.
2021.07.01 View 7542
Prof. Sang Wan Lee Selected for 2021 IBM Academic Award Professor Sang Wan Lee from the Department of Bio and Brain Engineering was selected as the recipient of the 2021 IBM Global University Program Academic Award. The award recognizes individual faculty members whose emerging science and technology contains significant interest for universities and IBM. Professor Lee, whose research focuses on artificial intelligence and computational neuroscience, won the award for his research proposal titled A Neuroscience-Inspired Approach for Metacognitive Reinforcement Learning. IBM provides a gift of $40,000 to the recipient’s institution in recognition of the selection of the project but not as a contract for services. Professor Lee’s project aims to exploit the unique characteristics of human reinforcement learning. Specifically, he plans to examines the hypothesis that metacognition, a human’s ability to estimate their uncertainty level, serves to guide sample-efficient and near-optimal exploration, making it possible to achieve an optimal balance between model-based and model-free reinforcement learning. He was also selected as the winner of the Google Research Award in 2016 and has been working with DeepMind and University College London to conduct basic research on decision-making brain science to establish a theory on frontal lobe meta-enhance learning. "We plan to conduct joint research for utilizing brain-based artificial intelligence technology and frontal lobe meta-enhanced learning technology modeling in collaboration with an international research team including IBM, DeepMind, MIT, and Oxford,” Professor Lee said.
2021.06.25 View 9199
Wearable Device to Monitor Sweat in Real Time An on-skin platform for the wireless monitoring of flow rate, cumulative loss, and temperature of sweat in real time An electronic patch can monitor your sweating and check your health status. Even more, the soft microfluidic device that adheres to the surface of the skin, captures, stores, and performs biomarker analysis of sweat as it is released through the eccrine glands. This wearable and wireless electronic device developed by Professor Kyeongha Kwon and her collaborators is a digital and wireless platform that could help track the so-called ‘filling process’ of sweat without having to visually examine the device. The platform was integrated with microfluidic systems to analyze the sweat’s components. To monitor the sweat release rate in real time, the researchers created a ‘thermal flow sensing module.’ They designed a sophisticated microfluidic channel to allow the collected sweat to flow through a narrow passage and a heat source was placed on the outer surface of the channel to induce a heat exchange between the sweat and the heated channel. As a result, the researchers could develop a wireless electronic patch that can measure the temperature difference in a specific location upstream and downstream of the heat source with an electronic circuit and convert it into a digital signal to measure the sweat release rate in real time. The patch accurately measured the perspiration rate in the range of 0-5 microliters/minute (μl/min), which was considered physiologically significant. The sensor can measure the flow of sweat directly and then use the information it collected to quantify total sweat loss. Moreover, the device features advanced microfluidic systems and colorimetric chemical reagents to gather pH measurements and determine the concentration of chloride, creatinine, and glucose in a user's sweat. Professor Kwon said that these indicators could be used to diagnose various diseases related with sweating such as cystic fibrosis, diabetes, kidney dysfunction, and metabolic alkalosis. “As the sweat flowing in the microfluidic channel is completely separated from the electronic circuit, the new patch overcame the shortcomings of existing flow rate measuring devices, which were vulnerable to corrosion and aging,” she explained. The patch can be easily attached to the skin with flexible circuit board printing technology and silicone sealing technology. It has an additional sensor that detects changes in skin temperature. Using a smartphone app, a user can check the data measured by the wearable patch in real time. Professor Kwon added, “This patch can be widely used for personal hydration strategies, the detection of dehydration symptoms, and other health management purposes. It can also be used in a systematic drug delivery system, such as for measuring the blood flow rate in blood vessels near the skin’s surface or measuring a drug’s release rate in real time to calculate the exact dosage.” -PublicationKyeongha Kwon, Jong Uk Kim, John A. Rogers, et al. “An on-skin platform for wireless monitoring of flow rate, cumulative loss and temperature of sweat in real time.” Nature Electronics (doi.org/10.1038/s41928-021-00556-2) -ProfileProfessor Kyeongha KwonSchool of Electrical EngineeringKAIST
2021.06.25 View 8055
Biomimetic Resonant Acoustic Sensor Detecting Far-Distant Voices Accurately to Hit the Market A KAIST research team led by Professor Keon Jae Lee from the Department of Materials Science and Engineering has developed a bioinspired flexible piezoelectric acoustic sensor with multi-resonant ultrathin piezoelectric membrane mimicking the basilar membrane of the human cochlea. The flexible acoustic sensor has been miniaturized for embedding into smartphones and the first commercial prototype is ready for accurate and far-distant voice detection. In 2018, Professor Lee presented the first concept of a flexible piezoelectric acoustic sensor, inspired by the fact that humans can accurately detect far-distant voices using a multi-resonant trapezoidal membrane with 20,000 hair cells. However, previous acoustic sensors could not be integrated into commercial products like smartphones and AI speakers due to their large device size. In this work, the research team fabricated a mobile-sized acoustic sensor by adopting ultrathin piezoelectric membranes with high sensitivity. Simulation studies proved that the ultrathin polymer underneath inorganic piezoelectric thin film can broaden the resonant bandwidth to cover the entire voice frequency range using seven channels. Based on this theory, the research team successfully demonstrated the miniaturized acoustic sensor mounted in commercial smartphones and AI speakers for machine learning-based biometric authentication and voice processing. (Please refer to the explanatory movie KAIST Flexible Piezoelectric Mobile Acoustic Sensor). The resonant mobile acoustic sensor has superior sensitivity and multi-channel signals compared to conventional condenser microphones with a single channel, and it has shown highly accurate and far-distant speaker identification with a small amount of voice training data. The error rate of speaker identification was significantly reduced by 56% (with 150 training datasets) and 75% (with 2,800 training datasets) compared to that of a MEMS condenser device. Professor Lee said, “Recently, Google has been targeting the ‘Wolverine Project’ on far-distant voice separation from multi-users for next-generation AI user interfaces. I expect that our multi-channel resonant acoustic sensor with abundant voice information is the best fit for this application. Currently, the mass production process is on the verge of completion, so we hope that this will be used in our daily lives very soon.” Professor Lee also established a startup company called Fronics Inc., located both in Korea and U.S. (branch office) to commercialize this flexible acoustic sensor and is seeking collaborations with global AI companies. These research results entitled “Biomimetic and Flexible Piezoelectric Mobile Acoustic Sensors with Multi-Resonant Ultrathin Structures for Machine Learning Biometrics” were published in Science Advances in 2021 (7, eabe5683). -Publication “Biomimetic and flexible piezoelectric mobile acoustic sensors with multiresonant ultrathin structures for machine learning biometrics,” Science Advances (DOI: 10.1126/sciadv.abe5683) -Profile Professor Keon Jae Lee Department of Materials Science and Engineering Flexible and Nanobio Device Lab http://fand.kaist.ac.kr/ KAIST
2021.06.14 View 8305
Krafton Matches Alumni Donations to Raise 11 Billion KRW for SW Developers Alumni donations from the School of Computing, including Baemin and Devsisters, continue to grow Alumni from the KAIST School of Computing who are current and former developers at the leading game company Krafton, established by KAIST alumna Byung-Gyu Chang, made an agreement to help raise 11 billion KRW during a ceremony on June 4. The funds raised in the matching grant will be used to nurture software developers. Krafton Chairman Chang donated 10 billion won last January. His donation inspired other alumni working at Krafton as well as its former developers. Eleven KAIST alumni raised 5.5 billion KRW in two months and discussed the matching grant idea with Chairman Chang. The Krafton matching grant ceremony was attended by President Kwang Hyung Lee, Provost and Executive Vice President Seung Seob Lee, Vice President for Research Sang Yup Lee, Head of the School of Computing Sukyoung Ryu, Krafton Chairman Byung-gyu Chang, and KAIST alumnus from Krafton Seung-woo Shin. Other alumni donors including Krafton CEO Changhan Kim joined the ceremony online. Krafton CEO Changhan Kim said, “Just as our alma mater played an important role in growing our company, we hope that our donation could help support good developers. This will not only help our company, but advance our industry.” KAIST and Krafton also signed a business agreement to foster competitive developers. Krafton said it plans to continue giving back to society through the matching grant program. Head of the School of Computing Sukyoung Ryu thanked Chairman Chang and alumni who took part in the fund raising, saying, “To take the lead in rapidly changing computer technology, we desperately need more top students, faculty members, and facilities. We need more resources and infrastructure for interdisciplinary research.” The School of Computing has seen significant growth recently. Its number of undergraduate students has increased from 450 in 2016 to more than 900 in 2021. With this donation, the school will expand its current buildings to provide diverse educational and mentoring programs in more spacious facilities. Seung-woo Shin (Class of ’92), who joined Krafton’s matching grant, said, “I have always been thankful for the people I met and what I learned at KAIST. I was moved by the idea of giving back to the school.” Seong-jung Ryu (Class of ’97) said, “This donation reminded me of the good times I had back then. I thought it was crucial that the department’s facilities be extended, so I naturally wanted to take part.” Alumni donations, especially from the School of Computing, have also continued to grow more recently. Woowa Brothers Corp. CEO Beom-Jun Kim, the developer of the meal delivery app ‘Baemin’ donated 100 million KRW in April. Baemin became the most used app in the country during the COVID-19 pandemic. He explained, “I have been thinking about ways to give something to the next generation, rather than ‘paying back’ those who helped me in the past.” Encouraged by Baemin’s donation, alumni couple Ha-Yeon Seo and Dong-Hun Hahn from the School of Computing and eleven alumni engineers working at Devsisters Corp. also followed suit.
2021.06.09 View 8273
Natural Rainbow Colorants Microbially Produced Integrated strategies of systems metabolic engineering and membrane engineering led to the production of natural rainbow colorants comprising seven natural colorants from bacteria for the first time A research group at KAIST has engineered bacterial strains capable of producing three carotenoids and four violacein derivatives, completing the seven colors in the rainbow spectrum. The research team integrated systems metabolic engineering and membrane engineering strategies for the production of seven natural rainbow colorants in engineered Escherichia coli strains. The strategies will be also useful for the efficient production of other industrially important natural products used in the food, pharmaceutical, and cosmetic industries. Colorants are widely used in our lives and are directly related to human health when we eat food additives and wear cosmetics. However, most of these colorants are made from petroleum, causing unexpected side effects and health problems. Furthermore, they raise environmental concerns such as water pollution from dyeing fabric in the textiles industry. For these reasons, the demand for the production of natural colorants using microorganisms has increased, but could not be readily realized due to the high cost and low yield of the bioprocesses. These challenges inspired the metabolic engineers at KAIST including researchers Dr. Dongsoo Yang and Dr. Seon Young Park, and Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering. The team reported the study entitled “Production of rainbow colorants by metabolically engineered Escherichia coli” in Advanced Science online on May 5. It was selected as the journal cover of the July 7 issue. This research reports for the first time the production of rainbow colorants comprising three carotenoids and four violacein derivatives from glucose or glycerol via systems metabolic engineering and membrane engineering. The research group focused on the production of hydrophobic natural colorants useful for lipophilic food and dyeing garments. First, using systems metabolic engineering, which is an integrated technology to engineer the metabolism of a microorganism, three carotenoids comprising astaxanthin (red), -carotene (orange), and zeaxanthin (yellow), and four violacein derivatives comprising proviolacein (green), prodeoxyviolacein (blue), violacein (navy), and deoxyviolacein (purple) could be produced. Thus, the production of natural colorants covering the complete rainbow spectrum was achieved. When hydrophobic colorants are produced from microorganisms, the colorants are accumulated inside the cell. As the accumulation capacity is limited, the hydrophobic colorants could not be produced with concentrations higher than the limit. In this regard, the researchers engineered the cell morphology and generated inner-membrane vesicles (spherical membranous structures) to increase the intracellular capacity for accumulating the natural colorants. To further promote production, the researchers generated outer-membrane vesicles to secrete the natural colorants, thus succeeding in efficiently producing all of seven rainbow colorants. It was even more impressive that the production of natural green and navy colorants was achieved for the first time. “The production of the seven natural rainbow colorants that can replace the current petroleum-based synthetic colorants was achieved for the first time,” said Dr. Dongsoo Yang. He explained that another important point of the research is that integrated metabolic engineering strategies developed from this study can be generally applicable for the efficient production of other natural products useful as pharmaceuticals or nutraceuticals. “As maintaining good health in an aging society is becoming increasingly important, we expect that the technology and strategies developed here will play pivotal roles in producing other valuable natural products of medical or nutritional importance,” explained Distinguished Professor Lee. This work was supported by the "Cooperative Research Program for Agriculture Science & Technology Development (Project No. PJ01550602)" Rural Development Administration, Republic of Korea. -Publication:Dongsoo Yang, Seon Young Park, and Sang Yup Lee. Production of rainbow colorants by metabolically engineered Escherichia coli. Advanced Science, 2100743. -Profile Distinguished Professor Sang Yup LeeMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.kr Department of Chemical and Biomolecular EngineeringKAIST
2021.06.09 View 8776
Ultrafast, on-Chip PCR Could Speed Up Diagnoses during Pandemics A rapid point-of-care diagnostic plasmofluidic chip can deliver result in only 8 minutes Reverse transcription-polymerase chain reaction (RT-PCR) has been the gold standard for diagnosis during the COVID-19 pandemic. However, the PCR portion of the test requires bulky, expensive machines and takes about an hour to complete, making it difficult to quickly diagnose someone at a testing site. Now, researchers at KAIST have developed a plasmofluidic chip that can perform PCR in only about 8 minutes, which could speed up diagnoses during current and future pandemics. The rapid diagnosis of COVID-19 and other highly contagious viral diseases is important for timely medical care, quarantining and contact tracing. Currently, RT-PCR uses enzymes to reverse transcribe tiny amounts of viral RNA to DNA, and then amplifies the DNA so that it can be detected by a fluorescent probe. It is the most sensitive and reliable diagnostic method. But because the PCR portion of the test requires 30-40 cycles of heating and cooling in special machines, it takes about an hour to perform, and samples must typically be sent away to a lab, meaning that a patient usually has to wait a day or two to receive their diagnosis. Professor Ki-Hun Jeong at the Department of Bio and Brain Engineering and his colleagues wanted to develop a plasmofluidic PCR chip that could quickly heat and cool miniscule volumes of liquids, allowing accurate point-of-care diagnoses in a fraction of the time. The research was reported in ACS Nano on May 19. The researchers devised a postage stamp-sized polydimethylsiloxane chip with a microchamber array for the PCR reactions. When a drop of a sample is added to the chip, a vacuum pulls the liquid into the microchambers, which are positioned above glass nanopillars with gold nanoislands. Any microbubbles, which could interfere with the PCR reaction, diffuse out through an air-permeable wall. When a white LED is turned on beneath the chip, the gold nanoislands on the nanopillars quickly convert light to heat, and then rapidly cool when the light is switched off. The researchers tested the device on a piece of DNA containing a SARS-CoV-2 gene, accomplishing 40 heating and cooling cycles and fluorescence detection in only 5 minutes, with an additional 3 minutes for sample loading. The amplification efficiency was 91%, whereas a comparable conventional PCR process has an efficiency of 98%. With the reverse transcriptase step added prior to sample loading, the entire testing time with the new method could take 10-13 minutes, as opposed to about an hour for typical RT-PCR testing. The new device could provide many opportunities for rapid point-of-care diagnostics during a pandemic, the researchers say. -Publication Ultrafast and Real-Time Nanoplasmonic On-Chip Polymerase Chain Reaction for Rapid and Quantitative Molecular Diagnostics ACS Nano (https://doi.org/10.1021/acsnano.1c02154) -Professor Ki-Hun Jeong Biophotonics Laboratory https://biophotonics.kaist.ac.kr/ Department of Bio and Brain Engineeinrg KAIST
2021.06.08 View 8332
KAIST to join Deep Space Exploration Project KAIST agreed to launch the Deep Space Exploration Research Consortium with two key leading aerospace research institutes, the Korea Aerospace Research Institute (KARI) and the Korea Astronomy and Space Science Institute (KASI) during a recent meeting at the KAIST campus. President Kwang Hyung Lee, KARI President Sang-Yool Lee, KASI President Young-Deuk Park, and Vice Minister of Science and ICT Hong-taek Yong attended the meeting to discuss medium- and long-term deep space exploration plans and collaborations. The three entities have cooperated in scientific research for the last 30 years during which Korea has been developing its space exploration expertise. They signed the MoU for Cooperation for R&D and Industrialization on Deep Space Exploration’ last December. The research consortium will share and discuss research plans for space science research and exploration technology, and contribute to planning the nation’s deep space exploration. At the meeting, KAIST reported its plans to return KITSAT-1 to Earth, Korea’s first satellite using local technology, and to explore the radiation belt (the Van Allen belt) around Earth. KAIST launched Korea’s first satellite KITSAT-1 in 1992. Meanwhile, KARI shared their plans to launch a lunar landing module using a Korean Space Launch Vehicle by 2030 and explained the current technologies and research related to a lunar landing and space exploration. Based on the payload technology it has been building on for the last 20 years, KASI emphasized the importance of research for deep space exploration in relation to the formation of the universe and the origin of mankind. Vice Minister of Science and Technology Yong also stressed that “to enhance Korea’s capabilities for space research after launching our space launch vehicle, Nuri, in October, there must be continued efforts and preparation for higher level space research, including space exploration planning. The various experts’ opinions discussed in today’s meeting will be taken into consideration for governmental policies related to the ‘National Space Exploration Roadmap’ to be established in the latter half of this year.”
2021.06.07 View 6529
What Guides Habitual Seeking Behavior Explained A new role of the ventral striatum explains habitual seeking behavior Researchers have been investigating how the brain controls habitual seeking behaviors such as addiction. A recent study by Professor Sue-Hyun Lee from the Department of Bio and Brain Engineering revealed that a long-term value memory maintained in the ventral striatum in the brain is a neural basis of our habitual seeking behavior. This research was conducted in collaboration with the research team lead by Professor Hyoung F. Kim from Seoul National University. Given that addictive behavior is deemed a habitual one, this research provides new insights for developing therapeutic interventions for addiction. Habitual seeking behavior involves strong stimulus responses, mostly rapid and automatic ones. The ventral striatum in the brain has been thought to be important for value learning and addictive behaviors. However, it was unclear if the ventral striatum processes and retains long-term memories that guide habitual seeking. Professor Lee’s team reported a new role of the human ventral striatum where long-term memory of high-valued objects are retained as a single representation and may be used to evaluate visual stimuli automatically to guide habitual behavior. “Our findings propose a role of the ventral striatum as a director that guides habitual behavior with the script of value information written in the past,” said Professor Lee. The research team investigated whether learned values were retained in the ventral striatum while the subjects passively viewed previously learned objects in the absence of any immediate outcome. Neural responses in the ventral striatum during the incidental perception of learned objects were examined using fMRI and single-unit recording. The study found significant value discrimination responses in the ventral striatum after learning and a retention period of several days. Moreover, the similarity of neural representations for good objects increased after learning, an outcome positively correlated with the habitual seeking response for good objects. “These findings suggest that the ventral striatum plays a role in automatic evaluations of objects based on the neural representation of positive values retained since learning, to guide habitual seeking behaviors,” explained Professor Lee. “We will fully investigate the function of different parts of the entire basal ganglia including the ventral striatum. We also expect that this understanding may lead to the development of better treatment for mental illnesses related to habitual behaviors or addiction problems.” This study, supported by the National Research Foundation of Korea, was reported at Nature Communications (https://doi.org/10.1038/s41467-021-22335-5.) -ProfileProfessor Sue-Hyun LeeDepartment of Bio and Brain EngineeringMemory and Cognition Laboratoryhttp://memory.kaist.ac.kr/lecture KAIST
2021.06.03 View 8078
Identification of How Chemotherapy Drug Works Could Deliver Personalized Cancer Treatment The chemotherapy drug decitabine is commonly used to treat patients with blood cancers, but its response rate is somewhat low. Researchers have now identified why this is the case, opening the door to more personalized cancer therapies for those with these types of cancers, and perhaps further afield. Researchers have identified the genetic and molecular mechanisms within cells that make the chemotherapy drug decitabine—used to treat patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) —work for some patients but not others. The findings should assist clinicians in developing more patient-specific treatment strategies. The findings were published in the Proceedings of the National Academies of Science on March 30. The chemotherapy drug decitabine, also known by its brand name Dacogen, works by modifying our DNA that in turn switches on genes that stop the cancer cells from growing and replicating. However, decitabine’s response rate is somewhat low (showing improvement in just 30-35% of patients), which leaves something of a mystery as to why it works well for some patients but not for others. To find out why this happens, researchers from the KAIST investigated the molecular mediators that are involved with regulating the effects of the drug. Decitabine works to activate the production of endogenous retroviruses (ERVs), which in turn induces an immune response. ERVs are viruses that long ago inserted dormant copies of themselves into the human genome. Decitabine in essence, ‘reactivates’ these viral elements and produces double-stranded RNAs (dsRNAs) that the immune system views as a foreign body. “However, the mechanisms involved in this process, in particular how production and transport of these ERV dsRNAs were regulated within the cell were understudied,” said corresponding author Yoosik Kim, professor in the Department of Chemical and Biomolecular Engineering at KAIST. “So to explain why decitabine works in some patients but not others, we investigated what these molecular mechanisms were,” added Kim. To do so, the researchers used image-based RNA interference (RNAi) screening. This is a relatively new technique in which specific sequences within a genome are knocked out of action or “downregulated.” Large-scale screening, which can be performed in cultured cells or within live organisms, works to investigate the function of different genes. The KAIST researchers collaborated with the Institut Pasteur Korea to analyze the effect of downregulating genes that recognize ERV dsRNAs and could be involved in the cellular response to decitabine. From these initial screening results, they performed an even more detailed downregulation screening analysis. Through the screening, they were able to identify two particular gene sequences involved in the production of an RNA-binding protein called Staufen1 and the production of a strand of RNA that does not in turn produce any proteins called TINCR that play a key regulatory role in response to the drug. Staufen1 binds directly to dsRNAs and stabilizes them in concert with the TINCR. If a patient is not producing sufficient Staufen1 and TINCR, then the dsRNA viral mimics quickly degrade before the immune system can spot them. And, crucially for cancer therapy, this means that patients with lower expression (activation) of these sequences will show inferior response to decitabine. Indeed, the researchers confirmed that MDS/AML patients with low Staufen1 and TINCR expression did not benefit from decitabine therapy. “We can now isolate patients who will not benefit from the therapy and direct them to a different type of therapy,” said first author Yongsuk Ku. “This serves as an important step toward developing a patient-specific treatment cancer strategy.” As the researchers used patient samples taken from bone marrow, the next step will be to try to develop a testing method that can identify the problem from just blood samples, which are much easier to acquire from patients. The team plans to investigate if the analysis can be extended to patients with solid tumors in addition to those with blood cancers. -Profile Professor Yoosik Kim https://qcbio.kaist.ac.kr/ Department of Chemical and Biomolecular Engineering KAIST -Publication Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs, PNAS
2021.05.24 View 8305
Gut Hormone Triggers Craving for More Proteins - Revelations from a fly study could improve our understanding of protein malnutrition in humans. - A new study led by KAIST researchers using fruit flies reveals how protein deficiency in the diet triggers cross talk between the gut and brain to induce a desire to eat foods rich in proteins or essential amino acids. This finding reported in the May 5 issue of Nature can lead to a better understanding of malnutrition in humans. “All organisms require a balanced intake of carbohydrates, proteins, and fats for their well being,” explained KAIST neuroscientist and professor Greg Seong-Bae Suh. “Taking in sufficient calories alone won’t do the job, as it can still lead to severe forms of malnutrition including kwashiorkor, if the diet does not include enough proteins,” he added. Scientists already knew that inadequate protein intake in organisms causes a preferential choice of foods rich in proteins or essential amino acids but they didn’t know precisely how this happens. A group of researchers led by Professor Suh at KAIST and Professor Won-Jae Lee at Seoul National University (SNU) investigated this process in flies by examining the effects of different genes on food preference following protein deprivation. The group found that protein deprivation triggered the release of a gut hormone called neuropeptide CNMamide (CNMa) from a specific population of enterocytes - the intestine lining cells. Until now, scientists have known that enterocytes release digestive enzymes into the intestine to help digest and absorb nutrients in the gut. “Our study showed that enterocytes have a more complex role than we previously thought,” said Professor Suh. Enterocytes respond to protein deprivation by releasing CNMa that conveys the nutrient status in the gut to the CNMa receptors on nerve cells in the brain. This then triggers a desire to eat foods containing essential amino acids. Interestingly, the KAIST-SNU team also found that the microbiome - Acetobacter bacteria - present in the gut produces amino acids that can compensate for mild protein deficit in the diet. This basal level of amino acids provided by the microbiome modifies CNMa release and tempers the flies’ compensatory desire to ingest more proteins. The research team was able to further clarify two signalling pathways that respond to protein loss from the diet and ultimately produce the CNMa hormone in these specific enterocytes. The team said that further studies are still needed to understand how CNMa communicates with its receptors in the brain, and whether this happens by directly activating nerve cells that link the gut to the brain or by indirectly activating the brain through blood circulation. Their research could provide insights into the understanding of similar process in mammals including humans. “We chose to investigate a simple organism, the fly, which would make it easier for us to identify and characterize key nutrient sensors. Because all organisms have cravings for needed nutrients, the nutrient sensors and their pathways we identified in flies would also be relevant to those in mammals. We believe that this research will greatly advance our understanding of the causes of metabolic disease and eating-related disorders,” Professor Suh added. This work was supported by the Samsung Science and Technology Foundation (SSTF) and the National Research Foundation (NRF) of Korea. Publication: Kim, B., et al. (2021) Response of the Drosophila microbiome– gut–brain axis to amino acid deficit. Nature. Available online at https://doi.org/10.1038/s41586-021-03522-2 Profile: Greg Seong-Bae Suh, Ph.D Associate Professor seongbaesuh@kaist.ac.krLab of Neural Interoception https://www.suhlab-neuralinteroception.kaist.ac.kr/Department of Biological Sciences https://bio.kaist.ac.kr/ Korea Advanced Institute of Science and Technology (KAIST) https:/kaist.ac.kr/en/ Daejeon 34141, Korea (END)
2021.05.17 View 6540

KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea T.042-350-2114 F.042-350-2210(2220)