KAIST

- Researchers report minimalistic principles for designing small molecules with multiple reactivities against dementia. - Sometimes the most complex problems actually have very simple solutions. A group of South Korean researchers reported an efficient and effective redox-based strategy for incorporating multiple functions into simple molecular reagents against neurodegenerative disorders. The team developed redox-active aromatic molecular reagents with a simple structural composition that can simultaneously target and modulate various pathogenic factors in complex neurodegenerative disorders such as Alzheimer’s disease. Alzheimer’s disease is one of the most prevalent neurodegenerative disorders, affecting one in ten people over the age of 65. Early-onset dementia also increasingly affects younger people. A number of pathogenic elements such as reactive oxygen species, amyloid-beta, and metal ions have been suggested as potential causes of Alzheimer’s disease. Each element itself can lead to Alzheimer’s disease, but interactions between them may also aggravate the patient’s condition or interfere with the appropriate clinical care.  For example, when interacting with amyloid-beta, metal ions foster the aggregation and accumulation of amyloid-beta peptides that can induce oxidative stress and toxicity in the brain and lead to neurodegeneration. Because these pathogenic factors of Alzheimer’s disease are intertwined, developing therapeutic agents that are capable of simultaneously regulating metal ion dyshomeostasis, amyloid-beta agglutination, and oxidative stress responses remains a key to halting the progression of the disease. A research team led by Professor Mi Hee Lim from the Department of Chemistry at KAIST demonstrated the feasibility of structure-mechanism-based molecular design for controlling a molecule’s chemical reactivity toward the various pathological factors of Alzheimer’s disease by tuning the redox properties of the molecule. This study, featured as the ‘ACS Editors’ Choice’ in the May 6th issue of the Journal of the American Chemical Society (JACS), was conducted in conjunction with KAIST Professor Mu-Hyun Baik’s group and Professor Joo-Young Lee’s group at the Asan Medical Center. Professor Lim and her collaborators rationally designed and generated 10 compact aromatic molecules presenting a range of redox potentials by adjusting the electronic distribution of the phenyl, phenylene, or pyridyl moiety to impart redox-dependent reactivities against the multiple pathogenic factors in Alzheimer’s disease. During the team’s biochemical and biophysical studies, these designed molecular reagents displayed redox-dependent reactivities against numerous desirable targets that are associated with Alzheimer’s disease such as free radicals, metal-free amyloid-beta, and metal-bound amyloid-beta. Further mechanistic results revealed that the redox properties of these designed molecular reagents were essential for their function. The team demonstrated that these reagents engaged in oxidative reactions with metal-free and metal-bound amyloid-beta and led to chemical modifications. The products of such oxidative transformations were observed to form covalent adducts with amyloid-beta and alter its aggregation. Moreover, the administration of the most promising candidate molecule significantly attenuated the amyloid pathology in the brains of Alzheimer’s disease transgenic mice and improved their cognitive defects. Professor Lim said, “This strategy is straightforward, time-saving, and cost-effective, and its effect is significant. We are excited to help enable the advancement of new therapeutic agents for neurodegenerative disorders, which can improve the lives of so many patients.” This work was supported by the National Research Foundation (NRF) of Korea, the Institute for Basic Science (IBS), and the Asan Institute for Life Sciences. Image credit: Professor Mi Hee Lim, KAIST Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of the news coverage of this paper only. Publication: Kim, M. et al. (2020) ‘Minimalistic Principles for Designing Small Molecules with Multiple Reactivities against Pathological Factors in Dementia.’ Journal of the American Chemical Society (JACS), Volume 142, Issue 18, pp.8183-8193. Available online at https://doi.org/10.1021/jacs.9b13100 Profile: Mi Hee Lim Professor miheelim@kaist.ac.kr http://sites.google.com/site/miheelimlab Lim Laboratory Department of Chemistry KAIST Profile: Mu-Hyun Baik Professor mbaik2805@kaist.ac.kr https://baik-laboratory.com/ Baik Laboratory Department of Chemistry KAIST Profile: Joo-Yong Lee Professor jlee@amc.seoul.kr Asan Institute for Life Sciences Asan Medical Center (END)

A research team led by Distinguished Professor Sang Yup Lee reported the production of a microbial strain capable of the massive production of succinic acid with the highest production efficiency to date. This strategy of integrating systems metabolic engineering with enzyme engineering will be useful for the production of industrially competitive bio-based chemicals. Their strategy was described in Nature Communications on April 23. The bio-based production of industrial chemicals from renewable non-food biomass has become increasingly important as a sustainable substitute for conventional petroleum-based production processes relying on fossil resources. Here, systems metabolic engineering, which is the key component for biorefinery technology, is utilized to effectively engineer the complex metabolic pathways of microorganisms to enable the efficient production of industrial chemicals. Succinic acid, a four-carbon dicarboxylic acid, is one of the most promising platform chemicals serving as a precursor for industrially important chemicals. Among microorganisms producing succinic acid, Mannheimia succiniciproducens has been proven to be one of the best strains for succinic acid production. The research team has developed a bio-based succinic acid production technology using the M. succiniciproducens strain isolated from the rumen of Korean cow for over 20 years and succeeded in developing a strain capable of producing succinic acid with the highest production efficiency. They carried out systems metabolic engineering to optimize the succinic acid production pathway of the M. succiniciproducens strain by determining the crystal structure of key enzymes important for succinic acid production and performing protein engineering to develop enzymes with better catalytic performance. As a result, 134 g per liter of succinic acid was produced from the fermentation of an engineered strain using glucose, glycerol, and carbon dioxide. They were able to achieve 21 g per liter per hour of succinic acid production, which is one of the key factors determining the economic feasibility of the overall production process. This is the world’s best succinic acid production efficiency reported to date. Previous production methods averaged 1~3 g per liter per hour. Distinguished professor Sang Yup Lee explained that his team’s work will significantly contribute to transforming the current petrochemical-based industry into an eco-friendly bio-based one. “Our research on the highly efficient bio-based production of succinic acid from renewable non-food resources and carbon dioxide has provided a basis for reducing our strong dependence on fossil resources, which is the main cause of the environmental crisis,” Professor Lee said. This work was supported by the Technology Development Program to Solve Climate Changes via Systems Metabolic Engineering for Biorefineries and the C1 Gas Refinery Program from the Ministry of Science and ICT through the National Research Foundation of Korea.

A team of South Korean researchers found that lactation can lower the incidence and reduce the risk of maternal postpartum diabetes. The researchers identified that lactation increases the mass and function of pancreatic beta cells through serotonin production. The team suggested that sustained improvements in pancreatic beta cells, which can last for years even after the cessation of lactation, improve mothers’ metabolic health in addition to providing health benefits for infants. Pregnancy imposes a substantial metabolic burden on women through weight gain and increased insulin resistance. Various other factors, including a history of gestational diabetes, maternal age, and obesity, further affect women’s risk of progressing to diabetes after delivery, and the risk of postpartum diabetes increases more in women who have had gestational diabetes and/or repeated deliveries. Diabetes-related complications include damage to blood vessels, which can lead to cardiovascular and cerebrovascular diseases such as heart attack and stroke, and problems with the nerves, eyes, kidneys, and many more. Since diabetes can pose a serious threat to mothers’ metabolic health, the management of maternal metabolic risk factors is important, especially in the peripartum period. Previous epidemiological studies have reported that lactation reduces the risk of postpartum diabetes, but the mechanisms underlying this benefit have remained elusive. The study, published in Science Translational Medicine on April 29, explains the biology underpinning this observation on the beneficial effects of lactation. Professor Hail Kim from the Graduate School of Medical Science and Engineering at KAIST led and jointly conducted the study in conjunction with researchers from the Seoul National University Bundang Hospital (SNUBH) and Chungnam National University (CNU) in Korea, and the University of California, San Francisco (UCSF) in the US. In their study, the team observed that the milk-secreting hormone ‘prolactin’ in lactating mothers not only promotes milk production, but also plays a major role in stimulating insulin-secreting pancreatic beta cells that regulate blood glucose in the body. The researchers also found that ‘serotonin’, known as a chemical that contributes to wellbeing and happiness, is produced in pancreatic beta cells during lactation. Serotonin in pancreatic beta cells act as an antioxidant and reduce oxidative stress, making mothers’ beta cells healthier. Serotonin also induces the proliferation of beta cells, thereby increasing the beta cell mass and helping maintain proper glucose levels. The research team conducted follow-up examinations on a total of 174 postpartum women, 85 lactated and 99 non-lactated, at two months postpartum and annually thereafter for at least three years. The results demonstrated that mothers who had undergone lactation improved pancreatic beta cell mass and function, and showed improved glucose homeostasis with approximately 20mg/dL lower glucose levels, thereby reducing the risk of postpartum diabetes in women. Surprisingly, this beneficial effect was maintained after the cessation of lactation, for more than three years after delivery. Professor Kim said, “We are happy to prove that lactation benefits female metabolic health by improving beta cell mass and function as well as glycemic control.” “Our future studies on the modulation of the molecular serotonergic pathway in accordance with the management of maternal metabolic risk factors may lead to new therapeutics to help prevent mothers from developing metabolic disorders,” he added. This work was supported by grants from the National Research Foundation (NRF) and the National Research Council of Science and Technology (NST) of Korea, the National Institutes of Health (NIH), the Larry L. Hillblom Foundation, and the Health Fellowship Foundation. Image credit: Professor Hail Kim, KAIST  Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only. Publication: Moon, J. H et al. (2020) ‘Lactation improves pancreatic β cell mass and function through serotonin production.’ Science Translational Medicine, 12, eaay0455. Available online at https://doi.org/10.1126/scitranslmed.aay0455 Profile: Hail Kim, MD, PhD hailkim@kaist.edu Associate Professor Graduate School of Medical Science and Engineering (GSMSE) Korea Advanced Institute of Science and Technology (KAIST) Profile: Hak Chul Jang, MD, PhD janghak@snu.ac.kr Professor Division of Endocrinology and Metabolism Seoul National University Bundang Hospital (SNUBH) President Korean Diabetes Association Profile: Joon Ho Moon, MD, PhD moonjoonho@gmail.com Clinical Fellow Division of Endocrinology and Metabolism SNUBH Profile: Hyeongseok Kim, MD, PhD hskim85kor@gmail.com Assistant Professor Chungnam National University (CNU) Profile: Professor Michael S. German, MD Michael.German@ucsf.edu Professor Diabetes Center University of California, San Francisco (UCSF) (END)

Researchers have confirmed that neuropeptide somatostatin can improve cognitive function in the brain. A research group of Professor Seung-Hee Lee from the Department of Biological Sciences at KAIST found that the application of neuropeptide somatostatin improves visual processing and cognitive behaviors by reducing excitatory inputs to parvalbumin-positive interneurons in the cortex.  This study, reported at Science Advances on April 22nd (EST), sheds a new light on the therapeutics of neurodegenerative diseases. According to a recent study in Korea, one in ten seniors over 65 is experiencing dementia-related symptoms in their daily lives such like memory loss, cognitive decline, and motion function disorders. Professor Lee believes that somatostatin treatment can be directly applied to the recovery of cognitive functions in Alzheimer’s disease patients. Professor Lee started this study noting the fact that the level of somatostatin expression was dramatically decreased in the cerebral cortex and cerebrospinal fluid of Alzheimer’s disease patients Somatostatin-expressing neurons in the cortex are known to exert the dendritic inhibition of pyramidal neurons via GABAergic transmission. Previous studies focused on their inhibitory effects on cortical circuits, but somatostatin-expressing neurons can co-release somatostatin upon activation. Despite the abundant expression of somatostatin and its receptors in the cerebral cortex, it was not known if somatostatin could modulate cognitive processing in the cortex. The research team demonstrated that the somatostatin treatment into the cerebral cortex could enhance visual processing and cognitive behaviors in mice. The research team combined behaviors, in vivo and in vitro electrophysiology, and electron microscopy techniques to reveal how the activation of somatostatin receptors in vivo enhanced the ability of visual recognition in animals. Interestingly, somatostatin release can reduce excitatory synaptic transmission to another subtype of GABAergic interneurons, parvalbumin (PV)-expressing neurons. As somatostatin is a stable and safe neuropeptide expressed naturally in the mammalian brain, it was safe to be injected into the cortex and cerebrospinal fluid, showing a potential application to drug development for curing cognitive disorders in humans. Professor Lee said, “Our research confirmed the key role of the neuropeptide SST in modulating cortical function and enhancing cognitive ability in the mammalian brain. I hope new drugs can be developed based on the function of somatostatin to treat cognitive disabilities in many patients suffering from neurological disorders.” This study was supported by the National Research Foundation of Korea. Publication: Song, Y. H et al. (2020) ‘Somatostatin enhances visual processing and perception by suppressing excitatory inputs to parvalbumin-positive interneurons in V1’, Science Advances, 6(17). Available online at https://doi.org/10.1126/sciadv.aaz0517 Profile: Seung-Hee Lee Associate Professor shlee1@kaist.ac.kr https://sites.google.com/site/leelab2013/  Sensory Processing Lab (SPL) Department of Biological Sciences (BIO) Korea Advanced Institute of Science and Technology (KAIST) Profile: You-Hyang Song Researcher (Ph.D.) dbgidtm17@kaist.ac.kr SPL, KAIST BIO Profile: Yang-Sun Hwang Researcher (M.S.) hys940129@kaist.ac.kr SPL, KAIST BIO (END)

- A KAIST data scientist group responds to facts and rumors on COVID-19 for global awareness of the pandemic. - Like the novel coronavirus, rumors have no borders. The world is fighting to contain the pandemic, but we also have to deal with the appalling spread of an infodemic that is as contagious as the virus. This infodemic, a pandemic of false information, is bringing chaos and extreme fear to the general public. Professor Meeyoung Cha’s group at the School of Computing started a global campaign called ‘Facts before Rumors,’ to prevent the spread of false information from crossing borders. She explained, “We saw many rumors that had already been fact-checked long before in China and South Korea now begin to circulate in other countries, sometimes leading to detrimental results. We launched an official campaign, Facts before Rumors, to deliver COVID-19-related facts to countries where the number of cases is now increasing.” She released the first set of facts on March 26 via her Twitter account @nekozzang. Professor Cha, a data scientist who has focused on detecting global fake news, is now part of the COVID-19 AI Task Force at the Global Strategy Institute at KAIST. She is also leading the Data Science Group at the Institute for Basic Science (IBS) as Chief Investigator. Her research group worked in collaboration with the College of Nursing at Ewha Woman’s University to identify 15 claims about COVID-19 that circulated on social networks (SNS) and among the general public. The team fact-checked these claims based on information from the WHO and CDCs of Korea and the US. The research group is now working on translating the list of claims into Portuguese, Spanish, Persian, Chinese, Amharic, Hindi, and Vietnamese. Delivering facts before rumors, the team says, will help contain the disease and prevent any harm caused by misinformation. The pandemic, which spread in China and South Korea before arriving in Europe and the US, is now moving into South America, Africa, and Southeast Asia. “We would like to play a part in preventing the further spread of the disease with the provision of only scientifically vetted, truthful facts,” said the team. For this campaign, Professor Cha’s team investigated more than 200 rumored claims on COVID-19 in China during the early days of the pandemic.  These claims spread in different levels: while some were only relevant locally or in larger regions of China, others propagated in Asia and are now spreading to countries that are currently most affected by the disease. For example, the false claim which publicized that ‘Fireworks can help tame the virus in the air’ only spread in China. Other claims such as ‘Eating garlic helps people overcome the disease’ or ‘Gargling with salt water prevents the contraction of the disease,’ spread around the world even after being proved groundless. The team noted, however, that the times at which these claims propagate are different from one country to another. “This opens up an opportunity to debunk rumors in some countries, even before they start to emerge,” said Professor Cha. Kun-Woo Kim, a master’s candidate in the Department of Industrial Design who joined this campaign and designed the Facts before Rumors chart also expressed his hope that this campaign will help reduce the number of victims. He added, “I am very grateful to our scientists who quickly responded to the Fact Check in these challenging times.”

Professor Dongsu Han from the School of Electrical Engineering has been appointed as the program chair for the 16th Association for Computing Machinery’s International Conference on emerging Networking EXperiments and Technologies (ACM CoNEXT 2020). Professor Han is the first program chair to be appointed from an Asian institution. ACM CoNEXT is hosted by ACM SIGCOMM, ACM's Special Interest Group on Data Communications, which specializes in the field of communication and computer networks. Professor Han will serve as program co-chair along with Professor Anja Feldmann from the Max Planck Institute for Informatics. Together, they have appointed 40 world-leading researchers as program committee members for this conference, including Professor Song Min Kim from KAIST School of Electrical Engineering. Paper submissions for the conference can be made by the end of June, and the event itself is to take place from the 1st to 4th of December. Conference Website: https://conferences2.sigcomm.org/co-next/2020/#!/home (END)

KAIST joined the Universities Space Research Association (USRA) on May 4, and brought the Association to a total of 113 member universities. The expertise KAIST brings will broaden the Association’s collective strength in space-related science, technology, and engineering worldwide. Professor Hyosang Yoon from the Department of Aerospace Engineering will serve as the representative of KAIST to USRA.  KAIST was selected by USRA’s current university members, in recognition of its significant commitment in, and contributions to, the fields of space and aerospace research. Especially, KAIST have developed Korea's first satellite, KITSAT-1 in 1992, which paved the way for space research in Korea and helped the nation strengthen technological competitiveness in that field.  USRA was established in 1969 under the auspices of the National Academy of Sciences (NAS) of the United States. It is a non-profit corporation chartered to advance space-related science, technology, and engineering. USRA operates scientific institutes and facilities, and conducts other major research and educational programs, using federal funding. USRA also engages the university community and employs in-house scientific leadership, innovative research and development, and project management expertise. USRA’s President and CEO Dr. Jeffrey A. Isaacson said in his announcement, “We are delighted to welcome these two renowned universities as members. We look forward to their active engagement with, and contributions to, our Association.” President Isaacson visited KAIST on December 10 last year to discuss possible collaborations between two organizations.

Professor Sue-Hyun Lee from the Department of Bio and Brain Engineering joined the World Economic Forum (WEF)’s Young Scientists Community on May 26. The class of 2020 comprises 25 leading researchers from 14 countries across the world who are at the forefront of scientific problem-solving and social change. Professor Lee was the only Korean on this year’s roster. The WEF created the Young Scientists Community in 2008 to engage leaders from the public and private sectors with science and the role it plays in society. The WEF selects rising-star academics, 40 and under, from various fields every year, and helps them become stronger ambassadors for science, especially in tackling pressing global challenges including cybersecurity, climate change, poverty, and pandemics. Professor Lee is researching how memories are encoded, recalled, and updated, and how emotional processes affect human memory, in order to ultimately direct the development of therapeutic methods to treat mental disorders. She has made significant contributions to resolving ongoing debates over the maintenance and changes of memory traces in the brain. In recognition of her research excellence, leadership, and commitment to serving society, the President and the Dean of the College of Engineering at KAIST nominated Professor Lee to the WEF’s Class of 2020 Young Scientists Selection Committee. The Committee also acknowledged Professor Lee’s achievements and potential for expanding the boundaries of knowledge and practical applications of science, and accepted her into the Community. During her three-year membership in the Community, Professor Lee will be committed to participating in WEF-initiated activities and events related to promising therapeutic interventions for mental disorders and future directions of artificial intelligence. Seven of this year’s WEF Young Scientists are from Asia, including Professor Lee, while eight are based in Europe. Six study in the Americas, two work in South Africa, and the remaining two in the Middle East. Fourteen, more than half, of the newly announced 25 Young Scientists are women. (END)

Professor Tek-jin Nam from the Department of Industrial Design was elected to serve on the first International Advisory Council (IAC) of the Design Research Society (DRS). The DRS, an academic society in the field of design research, was founded in the UK in 1966 with the mission of developing and promoting design research. The IAC is newly established under the new DRS governance structure, and its members are selected from distinguished design researchers recommended by DRS members around the globe. The new IAC members will carry out various activities offered by the DRS, which include innovating design research, strengthening the design researchers’ network and developing policies to nurture new researchers.

Professor Youngchul Kim from the Department of Civil and Environmental Engineering, who is also the Director of the Smart City Research Center at KAIST, was appointed as a commissioner of the 6th Presidential Commission on Architecture Policy on May 19. Professor Kim will contribute to coordinating and deliberating national architecture and urban development policies. He will serve a two-year term beginning this month. The Presidential Commission on Architecture Policy is made up of 30 commissioners. Nineteen members, including Professor Kim, are experts from the private sector, and the rest include the Minister of Land, Infrastructure, and Transport, the Minister for Environment, and other government officials. The non-governmental commissioners represent a diverse mixture of genders, ages, and regions for the balanced development of the nation. (END)