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Astrocytes Eat Connections to Maintain Plasticity in Adult Brains
Developing brains constantly sprout new neuronal connections called synapses as they learn and remember. Important connections — the ones that are repeatedly introduced, such as how to avoid danger — are nurtured and reinforced, while connections deemed unnecessary are pruned away. Adult brains undergo similar pruning, but it was unclear how or why synapses in the adult brain get eliminated. Now, a team of KAIST researchers has found the mechanism underlying plasticity and, potentially, neurological disorders in adult brains. They published their findings on December 23 in Nature. “Our findings have profound implications for our understanding of how neural circuits change during learning and memory, as well as in diseases,” said paper author Won-Suk Chung, an assistant professor in the Department of Biological Sciences at KAIST. “Changes in synapse number have strong association with the prevalence of various neurological disorders, such as autism spectrum disorder, schizophrenia, frontotemporal dementia, and several forms of seizures.” Gray matter in the brain contains microglia and astrocytes, two complementary cells that, among other things, support neurons and synapses. Microglial are a frontline immunity defense, responsible for eating pathogens and dead cells, and astrocytes are star-shaped cells that help structure the brain and maintain homeostasis by helping to control signaling between neurons. According to Professor Chung, it is generally thought that microglial eat synapses as part of its clean-up effort in a process known as phagocytosis. “Using novel tools, we show that, for the first time, it is astrocytes and not microglia that constantly eliminate excessive and unnecessary adult excitatory synaptic connections in response to neuronal activity,” Professor Chung said. “Our paper challenges the general consensus in this field that microglia are the primary synapse phagocytes that control synapse numbers in the brain.” Professor Chung and his team developed a molecular sensor to detect synapse elimination by glial cells and quantified how often and by which type of cell synapses were eliminated. They also deployed it in a mouse model without MEGF10, the gene that allows astrocytes to eliminate synapses. Adult animals with this defective astrocytic phagocytosis had unusually increased excitatory synapse numbers in the hippocampus. Through a collaboration with Dr. Hyungju Park at KBRI, they showed that these increased excitatory synapses are functionally impaired, which cause defective learning and memory formation in MEGF10 deleted animals. “Through this process, we show that, at least in the adult hippocampal CA1 region, astrocytes are the major player in eliminating synapses, and this astrocytic function is essential for controlling synapse number and plasticity,” Chung said. Professor Chung noted that researchers are only beginning to understand how synapse elimination affects maturation and homeostasis in the brain. In his group’s preliminary data in other brain regions, it appears that each region has different rates of synaptic elimination by astrocytes. They suspect a variety of internal and external factors are influencing how astrocytes modulate each regional circuit, and plan to elucidate these variables. “Our long-term goal is understanding how astrocyte-mediated synapse turnover affects the initiation and progression of various neurological disorders,” Professor Chung said. “It is intriguing to postulate that modulating astrocytic phagocytosis to restore synaptic connectivity may be a novel strategy in treating various brain disorders.” This work was supported by the Samsung Science & Technology Foundation, the National Research Foundation of Korea, and the Korea Brain Research Institute basic research program. Other contributors include Joon-Hyuk Lee and Se Young Lee, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST); Ji-young Kim, Hyoeun Lee and Hyungju Park; Research Group for Neurovascular Unit, Korea Brain Research Institute (KBRI); Seulgi Noh, and Ji Young Mun, Research Group for Neural Circuit, KBRI. Kim, Noh and Park are also affiliated with the Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST). -Profile Professor Won-Suk Chung Department of Biological Sciences Gliabiology Lab (https://www.kaistglia.org/) KAIST -Publication "Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis" https://doi.org/10.1038/s41586-020-03060-3
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. (END)
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 email@example.com 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 firstname.lastname@example.org GSMSE, KAIST
Microscopy Approach Poised to Offer New Insights into Liver Diseases
Researchers have developed a new way to visualize the progression of nonalcoholic fatty liver disease (NAFLD) in mouse models of the disease. The new microscopy method provides a high-resolution 3D view that could lead to important new insights into NAFLD, a condition in which too much fat is stored in the liver. “It is estimated that a quarter of the adult global population has NAFLD, yet an effective treatment strategy has not been found,” said professor Pilhan Kim from the Graduate School of Medical Science and Engineering at KAIST. “NAFLD is associated with obesity and type 2 diabetes and can sometimes progress to liver failure in serious case.” In the Optical Society (OSA) journal Biomedical Optics Express, Professor Kim and colleagues reported their new imaging technique and showed that it can be used to observe how tiny droplets of fat, or lipids, accumulate in the liver cells of living mice over time. “It has been challenging to find a treatment strategy for NAFLD because most studies examine excised liver tissue that represents just one timepoint in disease progression,” said Professor Kim. “Our technique can capture details of lipid accumulation over time, providing a highly useful research tool for identifying the multiple parameters that likely contribute to the disease and could be targeted with treatment.” Capturing the dynamics of NAFLD in living mouse models of the disease requires the ability to observe quickly changing interactions of biological components in intact tissue in real-time. To accomplish this, the researchers developed a custom intravital confocal and two-photon microscopy system that acquires images of multiple fluorescent labels at video-rate with cellular resolution. “With video-rate imaging capability, the continuous movement of liver tissue in live mice due to breathing and heart beating could be tracked in real time and precisely compensated,” said Professor Kim. “This provided motion-artifact free high-resolution images of cellular and sub-cellular sized individual lipid droplets.” The key to fast imaging was a polygonal mirror that rotated at more than 240 miles per hour to provide extremely fast laser scanning. The researchers also incorporated four different lasers and four high-sensitivity optical detectors into the setup so that they could acquire multi-color images to capture different color fluorescent probes used to label the lipid droplets and microvasculature in the livers of live mice. “Our approach can capture real-time changes in cell behavior and morphology, vascular structure and function, and the spatiotemporal localization of biological components while directly visualizing of lipid droplet development in NAFLD progression,” said Professor Kim. “It also allows the analysis of the highly complex behaviors of various immune cells as NAFLD progresses.” The researchers demonstrated their approach by using it to observe the development and spatial distribution of lipid droplets in individual mice with NAFLD induced by a methionine and choline-deficient diet. Next, they plan to use it to study how the liver microenvironment changes during NAFLD progression by imaging the same mouse over time. They also want to use their microscope technique to visualize various immune cells and lipid droplets to better understand the complex liver microenvironment in NAFLD progression.
Tinkering with Roundworm Proteins Offers Hope for Anti-aging Drugs
- The somatic nuclear protein kinase VRK-1 increases the worm’s lifespan through AMPK activation, and this mechanism can be applied to promoting human longevity, the study reveals. - KAIST researchers have been able to dial up and down creatures’ lifespans by altering the activity of proteins found in roundworm cells that tell them to convert sugar into energy when their cellular energy is running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings were published on July 1 in Science Advances. The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing, enjoyed a boost in its lifespan when researchers tinkered with a couple of proteins involved in monitoring the energy use by its cells. The proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status. Using a range of different biological research tools, including introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at KAIST were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. This gene has remained pretty much unchanged throughout evolution. Most complex organisms have this same gene, including humans. Lead author of the study Sangsoon Park and his colleagues confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks, and the inhibition of VRK-1 production reduced its lifespan. The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into the energy “currency” that cells spend to do everything they need to do. It is already known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in aging, and declines in the functioning of mitochondria are associated with age-related diseases. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals. When the research team performed similar tinkering with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms. “This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity, and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained Professor Lee. At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria. But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried out to better understand how VRK-1 works to activate AMPK, as well as figure out the precise mechanics of how AMPK controls cellular energy. This work was supported by the National Research Foundation (NRF), and the Ministry of Science and ICT (MSIT) of Korea. Image credit: Seung-Jae V. LEE, 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: Park, S., et al. (2020) ‘VRK-1 extends life span by activation of AMPK via phosphorylation’. Science Advances, Volume 6. No. 27, eaaw7824. Available online at https://doi.org/10.1126/sciadv.aaw7824 Profile: Seung-Jae V. Lee, Ph.D. Professor email@example.com https://sites.google.com/view/mgakaist Molecular Genetics of Aging Laboratory Department of Biological Sciences Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.krDaejeon 34141, Korea (END)
Professor J.H. Lee Wins the Innovators in Science Award
Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering won the Early-Career Scientist Award of the 2020 Innovators in Science Award. The New York Academy of Sciences administers the award in partnership with Takeda Pharmaceutical Company. The Innovators in Science Award grants two prizes of US $200,000 each year: one to an Early-Career Scientist and the other to a well-established Senior Scientist who have distinguished themselves for the creative thinking and impact of their rare disease research. The Senior Scientist Awardee is Dr. Adrian R. Krainer, at Cold Spring Harbor Laboratory whose research focused on the mechanisms and control of RNA splicing. Prof. Lee is recognized for his research investigating genetic mutations in stem cells in the brain that result in rare developmental brain disorders. He was the first to identify the causes of intractable epilepsies and has identified the genes responsible for several developmental brain disorders, including focal cortical dysplasia, Joubert syndrome—a disorder characterized by an underdevelopment of the brainstem—and hemimegaloencephaly, which is the abnormal enlargement of one side of the brain. “It is a great honor to be recognized by a jury of such globally respected scientists whom I greatly admire,” said Prof. Lee. “More importantly, this award validates research into brain somatic mutations as an important area of exploration to help patients suffering from devastating and untreatable neurological disorders.” Prof. Lee also is the Director of the National Creative Research Initiative Center for Brain Somatic Mutations, and Co-founder and Chief Technology Officer of SoVarGen, a biopharmaceutical company aiming to discover novel therapeutics and diagnosis for intractable central nervous system (CNS) diseases caused by low-level somatic mutation. The Innovators in Science Award is a limited submission competition in which research universities, academic institutions, government or non-profit institutions, or equivalent from around the globe with a well-established record of scientific excellence are invited to nominate their most promising Early-Career Scientists and their most outstanding Senior Scientists working in one of four selected therapeutic fields of neuroscience, gastroenterology, oncology, and regenerative medicine. The 2020 Winners will be honored at the virtual Innovators in Science Award Ceremony and Symposium in October 2020.
Breastfeeding Helps Prevent Mothers from Developing Diabetes after Childbirth
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 firstname.lastname@example.org Associate Professor Graduate School of Medical Science and Engineering (GSMSE) Korea Advanced Institute of Science and Technology (KAIST) Profile: Hak Chul Jang, MD, PhD email@example.com Professor Division of Endocrinology and Metabolism Seoul National University Bundang Hospital (SNUBH) President Korean Diabetes Association Profile: Joon Ho Moon, MD, PhD firstname.lastname@example.org Clinical Fellow Division of Endocrinology and Metabolism SNUBH Profile: Hyeongseok Kim, MD, PhD email@example.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)
A Study Finds Neuropeptide Somatostatin Enhances Visual Processing
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 firstname.lastname@example.org 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.) email@example.com SPL, KAIST BIO Profile: Yang-Sun Hwang Researcher (M.S.) firstname.lastname@example.org SPL, KAIST BIO (END)
Professor Youngseok Ju Awarded the 13th ASAN Award for Young Medical Scientists
Professor Youngseok Ju from the Graduate School of Medical Science and Engineering was selected for the 13th ASAN Award for Young Medical Scientists under the age of 40. Professor Ju will receive 50 million won in prize money. The ASAN Foundation established this Award in 2007 to encourage young medical scientists who accomplished outstanding achievements in basic and clinical medicine. The winners are chosen based on a comprehensive assessment of consistency and originality, domestic and international impact, and contributions to medical development and fostering future generations. Professor Ju is known for having identified the generation principle of cancer genome mutations. In particular, he is recognized for his contributions to the development of cancer prevention, diagnosis, and treatment, by having proven that some cases of lung cancer can occur from destructive changes in chromosomes in lung cells regardless of smoking. The award ceremony will be held on March 19 in Seoul. The other award will be given to Professor Yong-Ho Lee from the Yonsei University College of Medicine.
Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. ) The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection. For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications. The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin. “In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.” Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones. “This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said. By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy. The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP. “We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.” The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2. -Profile Professor Ji-Joon Song Department of Biological Sciences KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
A Single, Master Switch for Sugar Levels?
When a fly eats sugar, a single brain cell sends simultaneous messages to stimulate one hormone and inhibit another to control glucose levels in the body. Further research into this control system with remarkable precision could shed light on the neural mechanisms of diabetes and obesity in humans . A single neuron appears to monitor and control sugar levels in the fly body, according to research published this week in Nature. This new insight into the mechanisms in the fly brain that maintain a balance of two key hormones controlling glucose levels, insulin and glucagon, can provide a framework for understanding diabetes and obesity in humans. Neurons that sense and respond to glucose were identified more than 50 years ago, but what they do in our body has remained unclear. Researchers at the Korea Advanced Institute of Science and Technology (KAIST) and New York University School of Medicine have now found a single “glucose-sensing neuron” that appears to be the master controller in Drosophila, the vinegar fly, for maintaining an ideal glucose balance, called homeostasis. Professor Greg Seong-Bae Suh, Dr. Yangkyun Oh and colleagues identified a key neuron that is excited by glucose, which they called CN neuron. This CN neuron has a unique shape – it has an axon (which is used to transmit information to downstream cells) that is bifurcated. One branch projects to insulin-producing cells, and sends a signal triggering the secretion of the insulin equivalent in flies. The other branch projects to glucagon-producing cells and sends a signal inhibiting the secretion of the glucagon equivalent. When flies consume food, the levels of glucose in their body increase; this excites the CN neuron, which fires the simultaneous signals to stimulate insulin and inhibit glucagon secretion, thereby maintaining the appropriate balance between the hormones and sugar in the blood. The researchers were able to see this happening in the brain in real time by using a combination of cutting-edge fluorescent calcium imaging technology, as well as measuring hormone and sugar levels and applying highly sophisticated molecular genetic techniques. When flies were not fed, however, the researchers observed a reduction in the activity of CN neuron, a reduction in insulin secretion and an increase in glucagon secretion. These findings indicate that these key hormones are under the direct control of the glucose-sensing neuron. Furthermore, when they silenced the CN neuron rendering dysfunctional CN neuron in flies, these animals experienced an imbalance, resulting in hyperglycemia – high levels of sugars in the blood, similar to what is observed in diabetes in humans. This further suggests that the CN neuron is critical to maintaining glucose homeostasis in animals. While further research is required to investigate this process in humans, Suh notes this is a significant step forward in the fields of both neurobiology and endocrinology. “This work lays the foundation for translational research to better understand how this delicate regulatory process is affected by diabetes, obesity, excessive nutrition and diets high in sugar,” Suh said. Profile: Greg Seong-Bae Suh email@example.com Professor Department of Biological Sciences KAIST (Figure: A single glucose-excited CN neuron extends bifurcated axonal branches, one of which innervates insulin producing cells and stimulates their activity an the other axonal branch projects to glucagon producing cells and inhibits their activity.)
Professor Ki-Jun Yoon selected as the 2019 SUHF Young Investigator
< Professor Ki-Jun Yoon > Professor Ki-Jun Yoon from the Department of Biological Sciences was named one of four recipients of the 2019 Suh Kyung-Bae Science Foundation (SUHF) Young Investigator Awards. 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 83 research proposals from scientists across the nation, especially from those who had less than five years of experience as professors, and selected the four recipients, including Professor Yoon. Professor Yoon was recognized for his contributions to the advancement of research on how post-transcriptional mechanisms may modulate stem cell properties. His research project involves deciphering the molecular mechanisms controlling RNA metabolism in neural stem cells during normal development, and how alterations in RNA regulatory programs lead to human brain disorders. < (From left) Professor Joo-Hong Park, Professor Yuree Lee, Chairman and CEO Kyung-Bae Suh, Professor Eunjung Lee, Professor Ki-Jun Yoon, ⓒ Amorepacific Group > The other awards were given to Professor Joo-Hong Park and Professor Yuree Lee of Seoul National University, and Professor Eunjung Lee of Boston Children's Hospital and Harvard Medical School. The awards ceremony was held on September 18 at the Amorepacific Headquarters in Seoul. With these four new awardees, a total of 14 scientists have been named as SUHF Young Investigators to date. (END)
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