College+of+Life+Science+and+Bioengineering
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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
2020.01.07 View 8772 -
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
seongbaesuh@kaist.ac.kr
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.)
2019.10.24 View 16231 -
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.
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2019.09.23 View 7566 -
Two More Cross-generation Collaborative Labs Open
< President Sung-Chul Shin (sixth from the left) and Professor Sun Chang Kim (seventh from the left) at the signboard ceremony of KAIST BioDesigneering Laboratory >
KAIST opened two more cross-generation collaborative labs last month. KAIST BioDesigneering Laboratory headed by Professor Sun Chang Kim from the Department of Biological Sciences and Nanophotonics Laboratory led by Professor Yong-Hee Lee from the Department of Physics have been selected to receive 500 million KRW funding for five years.
A four-member selection committee including the former President of ETH Zürich Professor Emeritus Ralph Eichler and Professor Kwang-Soo Kim of Harvard Medical School conducted a three-month review and evaluation for this selection to be made. With these two new labs onboard, a total of six cross-generation collaborative labs will be operated on campus.
The operation of cross-generation collaborative labs has been in trial since March last year, as one of the KAIST’s Vision 2031 research innovation initiatives. This novel approach is to pair up senior and junior faculty members for sustaining research and academic achievements even after the senior researcher retires, so that the spectrum of knowledge and research competitiveness can be extended to future generations. The selected labs will be funded for five years, and the funding will be extended if necessary. KAIST will continue to select new labs every year.
One of this year’s selectees Professor Sun Chang Kim will be teamed up with Professor Byung-Kwan Cho from the same department and Professor Jung Kyoon Choi from the Department of Bio and Brain Engineering to collaborate in the fields of synthetic biology, systems biology, and genetic engineering. This group mainly aims at designing and synthesizing optimal genomes that can efficiently manufacture protein drug and biomedical active materials. They will also strive to secure large amounts of high-functioning natural active substances, new adhesive antibacterial peptides, and eco-friendly ecological restoration materials. It is expected that collaboration between these three multigenerational professors will help innovate their bio-convergence technology and further strengthen their international competitiveness in the global bio-market.
Another world-renowned scholar Professor Yong-Hee Lee of photonic crystal laser study will be joined by Professor Minkyo Seo from the same department and Professor Hansuek Lee from the Graduate School of Nanoscience and Technology. They will explore the extreme limits of light-material interaction based on optical micro/nano resonators, with the goal of developing future nonlinear optoelectronic and quantum optical devices. The knowledge and technology newly gained from the research are expected to provide an important platform for a diverse range of fields from quantum communications to biophysics.
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2019.09.06 View 8707 -
Professor Sang Gyu Kim Receives Yeochon Award for Ecology
Professor Sang-Gyu Kim from the Department of Biological Sciences was selected as the winner of the 12th Yeochon Award for Ecology presented by the Yeochon Association for Ecological Research.
The award was conferred on August 13 in Jeju at the annual conference co-hosted by the Ecological Society of Korea and the Yeochon Association for Ecological Research. Professor Kim received 10 million KRW in prize money.
Professor Kim was recognized for his achievements and contributions in studying herbivorous insects ‘rice weevils’ and their host plant ‘wild tobacco’, especially for having explored the known facts in traditional ecology at the molecular level. His findings are presented in his paper titled ‘Trichobaris weevils distinguish amongst toxic host plants by sensing volatiles that do not affect larval performance’ published in Molecular Ecology in July 2016.
Furthermore, Professor Kim’s research team is continuing their work to identify the ecological functions of plant metabolites as well as interactions between flowers and insect vectors at the molecular level. In doing so, the team edits genes in various plant species using the latest gene editing technology.
The Yeochon Award for Ecology was first established in 2005 with funds donated by a senior ecologist, the late Honorary Professor Joon-Ho Kim of Seoul National University. The award is named after the professor’s pen name “Yeochon” and is intended to encourage promising next-generation ecologists to produce outstanding research achievements in the field of basic ecology.
Professor Kim said, “I will take this award as encouragement to continue taking challenging risks to observe ecological phenomenon from a new perspective. I will continue my research with my students with joy and enthusiasm.”
2019.08.14 View 5332 -
New Members of KAST and Y-KAST 2019
(Professor Eui-Cheol Shin from the Graduate School of Medical Science and Engineering)
Professor Eui-Cheol Shin from the Graduate School of Medical Science and Engineering became a new fellow of the Korean Academy of Science and Technology (KAST) along with 25 other scientists in Korea. He is one of the top virus immunologists in Korea and has published a review article in Nature Reviews Immunology.
Meanwhile KAST selected and announced 26 young scientists under the age 43 who have shown great potential and the creativity to carry out next-generation research. The list of Y-KAST (Young Korean Academy of Science and Technology) includes six KAIST professors: Professor Ji Oon Lee from the Department of Mathematical Sciences, Professor Mi Hee Lim from the Department of Chemistry, Professor Shin-Hyun Kim from the Department of Chemical and Biomolecular Engineering, Professor Jung-Ryul Lee from the Department of Aerospace Engineering, Professor Hyunjoo Jenny Lee from the School of Electrical Engineering, and Professor Yeon Sik Jung from the Department of Materials Science and Engineering.
KAST conferred their fellowships and Y-KAST membership during the New Year Reception.
2019.01.22 View 7564 -
Professor Jeong-Ho Lee Named the KAISTian of 2018
(Professor Jeong-Ho Lee (right) poses with President Sung-Chul Shin)
Professor Jeong-Ho Lee from the Graduate School of Medical Science and Engineering was selected as the KAISTian of the Year of 2018. The award was established in 2001 and recognizes the most outstanding scholars who have made significant research and scholastic achievements during the year. Professor Lee was awarded during the New Year ceremony held in the auditorium on January 2.
Professor Lee has investigated mutations arising in the brain for decades and has published in renowned journals such as Nature, Nature Medicine, and Cell. Last August, Professor Lee reported breakthrough research on glioblastoma in Nature, giving insight into understanding how the mutation causing glioblastoma starts and suggested novel ways to treat glioblastoma, which was thought to be incurable. (Click for more)
Professor Lee’s Translational Neurogenetics Laboratory lab is investigating innovative diagnostics and therapeutics for untreatable brain disorders including intractable epilepsy and glioblastoma. To commercialize his technology, he established the tech-startup SoVarGen and now works as its CTO.
Professor Lee credited all his lab colleagues and staff. “I know all of this research would not have possible without their sweat and effort. I am happy to receive this honorable award on behalf of them.”
Remembering the beginning of his career at KAIST in 2012, Professor Lee said “KAIST seemed to be a very high and formidable barrier for me, after completing my medical education in Korea. I thank my department professors and colleagues who led me to focus on the research path that I really wanted. They provided everything for my research environment to help make good results.”
“I will continue to strive for promoting the well-being of humanity by addressing various incurable diseases as well as developing novel therapeutics. That will be the way to promote the stature of KAIST at home and abroad,” he added.
2019.01.02 View 4927 -
Professor Ju, to Receive Grants from HFSP
(Professor Young Seok Ju)
Professor Young Seok Ju from the Graduate School of Medical Science and Engineering was selected as a young investigator to receive research funds from the Human Frontiers Science Program.
The Human Frontiers Science Program (HFSP) was founded in 1989 with members of the G7 and European Union to stimulate innovative research in the field of life sciences.
Professor Ju placed third out of the eight teams that were selected from 158 applicants representing 60 countries. He is now the fourth Korean to receive a research grant as a young investigator. Professor Jae Kyoung Kim from the Department of Mathematical Sciences also received this prize last year, hence KAIST has produced grant recipients for two consecutive years.
Professor Ju is a medical doctor specializing in cancer genomics and computer biology. He has been studying somatic mutations and their functional consequences in human cancer in a bioinformatics way. He has published papers in international journals including Nature, Science, Genome Research, and Journal of Clinical Oncology.
With a title ‘Tracing AID/APOBEC- and MSI-mediated hyper-mutagenesis in the clonal evolution of gastric cancer,’ Professor Ju will receive 1.05 million dollars for three years along with Professor Bon-Kyoung Koo from the Institute of Molecular Biotechnology at Austrian Academy of Sciences, and Sinppert Hugo from University Medical Center Utrecht.
Professor Ju said, “As a young investigator, it is my great honor to receive this research fund from this organization. Through this internationally collaborative research, I will carry out groundbreaking research to understand the pathophysiology of cancers at a molecular level.”
2018.04.24 View 7229 -
Professor Gou Young Koh, 2018 Laureate of Ho-Am Prize
Distinguished Professor Gou Young Koh from the Graduate School of Medical Science and Engineering was appointed a 2018 laureate in medicine of the Ho-Am Prize by the Ho-Am Foundation. Professor Koh is a renowned expert in the field of tumor angiogenesis by exploring the hidden nature of capillary and lymphatic vessels in human organs.
He was recognized for demonstrating the effective reduction of tumor progression and metastasis via tumor vessel normalization. This counterintuitive study result is regarded as a stepping stone for a drug discovery to prevent microvascular diseases.
Besides Professor Koh, Professor Hee Oh from Yale University (Science), Professor Nam-Gyu Park from Sungkyunkwan University (Engineering), Opera Singer Kwangchul Youn (The Arts) and Sister Carla Kang (Community Service) received awards.
The Ho-Am Prize is presented to individuals who have contributed to academics, the arts, and social development, or furthered the welfare of humanity, and commemorates the noble spirit of public service espoused by the late Chairman Byung-chull Lee, who used the pen name Ho-Am.
It was established in 1990 by Kun-Hee Lee, the chairman of Samsung. Awards have been presented to 143 individuals worth a total of 24.4 billion KRW.
2018.04.11 View 7282 -
Two Professors Receive the Asan Medical Award
(Professor Ho Min Kim and Chair Profesor Eunjoon Kim (from far right)
Chair Professor Eunjoon Kim of the Department of Biological Sciences and Professor Ho Min Kim from the Graduate School of Medical Science & Engineering won the 11th Asan Medical Award in the areas of basic medicine and young medical scholar on March 21.
The Asan Medical Award has been recognizing the most distinguished scholars in the areas of basic and clinical medicines annually since 2007.
Chair Professor Kim won the 300 million KRW award in recognition of his research in the mechanism of synaptic brain dysfunction and its relation with neural diseases.
The young medical scholar’s award recognizes a promising scholar under the age of 40. Professor Kim won the award for identifying the key protein structure and molecular mechanism controlling immunocytes and neurons. He earned a 50 million KRW prize.
2018.03.26 View 7467 -
Professor Jin Woo Kim Wins the 14th Macrogen Scientist Award
Professor Jin Woo Kim of the Department of Biological Sciences at KAIST received the 14th Macrogen Scientist Award at the 2017 KSMCB International Conference held in COEX on September 12, 2017.
The award is given by the Korean Society for Molecular and Cellular Biology (KSMCB) and sponsored by Macrogen, a service provider of genome research. The award was established in 2004 to recognize biological scientists who have accomplished excellent performance in the field of basic life sciences.
Professor Kim has achieved outstanding research performances on nerve development, such as identifying the cause of senile retinal degenerative disease and finding retinal nerve cells that distinguish light and darkness in dark conditions.
Recently, he discovered intercellular communication, which controls the development of retinal neurons. His findings have contributed to addressing the principles of maintenance and regeneration of retinal neurons.
Since joining KAIST, he has presented approximately 20 papers and published in numerous international journals including Cell Reports, Genes and Development, and EMBO Journal. Moreover, he delivered special lectures at international conferences, universities, and institutes around the world.
2017.09.14 View 7370 -
Professor Dae-Sik Im to Head the Science, Technology and Innovation Office at the Ministry of Science & ICT
(Professor Dae-Sik Im of the Department of Biological Sciences)
Professor Dae-Sik Im of the Department of Biological Sciences, a renowned molecular cell biologist, was named to head the Science, Technology and Innovation Office in the Ministry of Science and ICT on August 31. He will be responsible for the oversight of national R&D projects as well as budget deliberation. Joining the KAIST faculty in 2002, he led the Creative Research Center of Cell Division and Differentiation at KAIST.
Announcing the nomination of Professor Im, Cheong Wa Dae spokesman Park Soo-Hyun said, “Professor Im will be the best person to lead the innovation of the research infrastructure system for basic research studies. We believe that his expertise and leadership will make a significant impact in enhancing the nation’s science and technology competitiveness. This vice minister position in the Ministry of Science and ICT was newly created in an effort to enhance national science and technology initiatives by President Moon Jae-In.
Professor Im said at the news conference, “I would like to make a sustainable, as well as credible, system ensuring the ingenuity of scientists in Korean labs. To this end, I will make every effort to enhance Korea’s innovative research environment in a way to maximize research achievements.”
2017.09.03 View 7917