Department+of+Bio+and+Brain+Engineering
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A Mechanism Underlying Most Common Cause of Epileptic Seizures Revealed
An interdisciplinary study shows that neurons carrying somatic mutations in MTOR can lead to focal epileptogenesis via non-cell-autonomous hyperexcitability of nearby nonmutated neurons
During fetal development, cells should migrate to the outer edge of the brain to form critical connections for information transfer and regulation in the body. When even a few cells fail to move to the correct location, the neurons become disorganized and this results in focal cortical dysplasia. This condition is the most common cause of seizures that cannot be controlled with medication in children and the second most common cause in adults.
Now, an interdisciplinary team studying neurogenetics, neural networks, and neurophysiology at KAIST has revealed how dysfunctions in even a small percentage of cells can cause disorder across the entire brain. They published their results on June 28 in Annals of Neurology.
The work builds on a previous finding, also by a KAIST scientists, who found that focal cortical dysplasia was caused by mutations in the cells involved in mTOR, a pathway that regulates signaling between neurons in the brain.
“Only 1 to 2% of neurons carrying mutations in the mTOR signaling pathway that regulates cell signaling in the brain have been found to include seizures in animal models of focal cortical dysplasia,” said Professor Jong-Woo Sohn from the Department of Biological Sciences. “The main challenge of this study was to explain how nearby non-mutated neurons are hyperexcitable.”
Initially, the researchers hypothesized that the mutated cells affected the number of excitatory and inhibitory synapses in all neurons, mutated or not. These neural gates can trigger or halt activity, respectively, in other neurons. Seizures are a result of extreme activity, called hyperexcitability. If the mutated cells upend the balance and result in more excitatory cells, the researchers thought, it made sense that the cells would be more susceptible to hyperexcitability and, as a result, seizures.
“Contrary to our expectations, the synaptic input balance was not changed in either the mutated or non-mutated neurons,” said Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering. “We turned our attention to a protein overproduced by mutated neurons.”
The protein is adenosine kinase, which lowers the concentration of adenosine. This naturally occurring compound is an anticonvulsant and works to relax vessels. In mice engineered to have focal cortical dysplasia, the researchers injected adenosine to replace the levels lowered by the protein. It worked and the neurons became less excitable.
“We demonstrated that augmentation of adenosine signaling could attenuate the excitability of non-mutated neurons,” said Professor Se-Bum Paik from the Department of Bio and Brain Engineering.
The effect on the non-mutated neurons was the surprising part, according to Paik. “The seizure-triggering hyperexcitability originated not in the mutation-carrying neurons, but instead in the nearby non-mutated neurons,” he said.
The mutated neurons excreted more adenosine kinase, reducing the adenosine levels in the local environment of all the cells. With less adenosine, the non-mutated neurons became hyperexcitable, leading to seizures.
“While we need further investigate into the relationship between the concentration of adenosine and the increased excitation of nearby neurons, our results support the medical use of drugs to activate adenosine signaling as a possible treatment pathway for focal cortical dysplasia,” Professor Lee said.
The Suh Kyungbae Foundation, the Korea Health Technology Research and Development Project, the Ministry of Health & Welfare, and the National Research Foundation in Korea funded this work.
-Publication:Koh, H.Y., Jang, J., Ju, S.H., Kim, R., Cho, G.-B., Kim, D.S., Sohn, J.-W., Paik, S.-B. and Lee, J.H. (2021), ‘Non–Cell Autonomous Epileptogenesis in Focal Cortical Dysplasia’ Annals of Neurology, 90: 285 299. (https://doi.org/10.1002/ana.26149)
-ProfileProfessor Jeong Ho Lee Translational Neurogenetics Labhttps://tnl.kaist.ac.kr/ Graduate School of Medical Science and Engineering KAIST
Professor Se-Bum Paik Visual System and Neural Network Laboratory http://vs.kaist.ac.kr/ Department of Bio and Brain EngineeringKAIST
Professor Jong-Woo Sohn Laboratory for Neurophysiology, https://sites.google.com/site/sohnlab2014/home Department of Biological SciencesKAIST
Dr. Hyun Yong Koh Translational Neurogenetics LabGraduate School of Medical Science and EngineeringKAIST
Dr. Jaeson Jang Ph.D.Visual System and Neural Network LaboratoryDepartment of Bio and Brain Engineering KAIST
Sang Hyeon Ju M.D.Laboratory for NeurophysiologyDepartment of Biological SciencesKAIST
2021.08.26 View 10374 -
Three Professors Named KAST Fellows
(Professor Dan Keun Sung at the center)
(Professor Y.H. Cho at the center)
(Professor K.H. Cho at the center)
The Korean Academy of Science and Technology (KAST) inducted three KAIST professors as fellows at the New Year’s ceremony held at KAST on January 12. They were among the 24 newly elected fellows of the most distinguished academy in Korea. The new fellows are Professor Dan Keun Sung of the School of Electrical Engineering, Professor Kwang-Hyun Cho of the Department of Bio and Brain Engineering, and Professor Yong-Hoon Cho of the Department of Physics.
Professor Sung was recognized for his lifetime academic achievements in fields related with network protocols and energy ICT. He also played a crucial role in launching the Korean satellites KITSAT-1,2,3 and the establishment of the Satellite Technology Research Center at KAIST.
Professor Y.H.Cho has been a pioneer in the field of low-dimensional semiconductor-powered quantum photonics that enables quantum optical research in solid state. He has been recognized as a renowned scholar in this field internationally.
Professor K.H.Cho has conducted original research that combines IT and BT in systems biology and has applied novel technologies of electronic modeling and computer simulation analysis for investigating complex life sciences. Professor Cho, who is in his 40s, is the youngest fellow among the newly inducted fellows.
2018.01.16 View 11785 -
ANSYS Korea Donates Engineering Simulation Software
ANSYS Korea made an in-kind donation of engineering simulation software, Multiphysics Campus Solution, to KAIST on March 24. ANSYS Korea donated 10,000 copies for education and 1,000 copies for research valued at about 4 billion KRW (about 200 billion KRW commercially).
The ANSYS software will benefit the engineering simulation work in nine departments and 60 labs for three years, including the departments of mechanical engineering, aerospace engineering, electrical engineering, civil and environmental engineering, nuclear and quantum engineering, chemical and bimolecular engineering, bio and brain engineering, materials science and engineering, and the Cho Chun Shik Graduate School of Green Transportation.
ANSYS is a global engineering simulation company. It provides ANSYS CAE (Computer Aided Engineering) software products in various industries in the world as well as various support, training, and consulting services. Deemed an exemplary model of university-industry R&D collaboration especially in the Industry 4.0 era, their donation will help create the best engineering education environment possible at KAIST.
ANSYS's multi-physics campus solution is a comprehensive software suite that spans the entire range of physics, providing access to virtually any field of engineering simulation that a design process requires. It expands the fields of fluids, structures, electromagnetics, and semiconductors. Undergraduates use it to learn physics principles and gain hands-on, real-world experience that can lead to a deeper understanding of engineering concepts. Postgraduate researchers apply simulation tools to solve complex engineering problems and produce data for their theses.
"Engineering simulations are playing a stronger role in science and engineering. ANSYS software will help our undergraduates and our researchers learn the principles of physics and deepen their understanding of engineering concepts. We hope this will serve as an instrumental tool for multidisciplinary studies, critical to fostering our students," said President Sung-Chul Shin.
ANSYS Korea CEO Yong-Won Cho added, "We sincerely hope our software will help KAIST students and researchers experience the best engineering education and achieve significant research results."
(Photo caption: President Shin (left) poses with ANSYS Korea CEO Yong-Won Cho at the donation ceremony on March 24 at KAIST)
2017.03.24 View 7565 -
Asia Pacific Biotech News' Special Coverage of Korean Biotechnology
The Asia Pacific Biotech News covered five major biotechnology research projects sponsored by the Korean government in the areas of biofuels, biomedicine, bio-nano healthcare, and biorefinery.
The Asia Pacific Biotech News (APBN), a monthly magazine based in Singapore, which offers comprehensive reports on the fields of pharmaceuticals, healthcare, and biotechnology, recently published a special feature on Korea’s biotechnology research and development (R&D) programs.
The magazine feature selected five research programs sponsored by the Korean government, which are either part of the Global Frontier or the Climate Change Technology Development Projects.
The programs are:
Systems Metabolic Engineering Research: Distinguished Professor Sang Yup Lee
of the Chemical and Biomolecular Engineering Department at the Korea Advanced
Institute of Science and Technology (KAIST) has been leading a research group to
develop biorefining technology using renewable non-food biomass to produce
chemicals, fuels, and materials that were largely drawn from fossil resources
through petrochemical refinery processes. Applying a systems metabolic
engineering approach, the group succeeded in modifying the metabolic pathways of
microorganisms. As a result, they produced, for the first time in the world,
engineered plastic raw materials and gasoline. The team also developed a technique
to produce butanol and succinic acid with a higher titer and yield using metabolically
engineered microorganisms.
Next-generation Biomass Research: Under the leadership of Professor Yong-
Keun Chang of the Chemical and Biomolecular Engineering Department at KAIST,
the research project, which belongs to the Global Frontier Project, develops biofuels
and bioproducts utilizing microalgae typically found in water and other marine
systems.
Convergence Research for Biomedicine: Professor Sung-Hoon Kim of Seoul
National University leads this project that develops targeted new drugs based on
convergence research strategies.
Bionano Healthcare Chip Research: Director Bong-Hyun Chung of the Korea
Research Institute of Bioscience and Biotechnology has integrated information and
communications technology, nanotechnology, and biotechnology to develop a
diagnostic kit that can screen toxic germs, virus, and toxic materials in a prompt
and accurate manner.
Biosynergy Research: Led by Professor Do-Hun Lee of the Bio and Brain
Engineering Department at KAIST, this research project develops new treatments
with a multi-target, multi-component approach in the context of systems biology
through an analysis of synergistic reactions between multi-compounds in traditional
East Asian medicine and human metabolites. In East Asian medicine, treatment and
caring of the human body are considered analogous to the politics of governing a
nation. Based on such system, the research focuses on designing a foundation for
the integration of traditional medicine with modern drug discovery and development.
Director Ilsub Baek at the Platform Technology Division of the Ministry of Science, ICT and Future Planning, Republic of Korea, who is responsible for the Global Frontier Program and the Technology to Solve Climate Change, said, “It is great to see that Asia Pacific Biotech News published an extensive coverage of Korea’s several key research programs on biotechnology as its first issue of this year. I am sure that these programs will lead to great outcomes to solve many worldwide pending issues including climate change and healthcare in the aging society.”
Professor Sang Yup Lee, who served as an editor of the feature, said, “At the request of the magazine, we have already published lead articles on our biotechnology research three times in the past in 2002, 2006, and 2011. I am pleased to see continued coverage of Korean biotechnology by the magazine because it recognizes the excellence of our research. Biotechnology has emerged as one of the strong fields that addresses important global issues such as climate change and sustainability.”
2016.02.04 View 11391 -
A Technology Holding Company Establishes Two Companies Based on Technologies Developed at KAIST
Mirae Holdings is a technology holding company created by four science and technology universities, KAIST, DIGIST (Daegu Gyeongbuk Institute of Science and Technology), GIST (Gwangju Institute of Science and Technology), and UNIST (Ulsan National Institute of Science and Technology) in 2014 to commercialize the universities’ research achievements. The company identifies promising technologies for commercialization, makes business plans, establishes venture capitals, and invests in startup companies.
Over the past year, Mirae Holdings has established two venture companies based on the technologies developed at KAIST. In September 2014, it founded Cresem Inc., a company used the anisotropic conductive film (ACF) bonding technology, which was developed by Professor Kyung-Wook Paik of the Material Science and Engineering Department at KAIST. Cresem provides a technology to bond electronic parts ultrasonically. The company is expected to have 860,000 USD worth of sales within the first year of its launching.
Last June, Mirae Holdings created another company, Doctor Kitchen, with the technology developed by Professor Gwan-Su Yi of the Bio and Brain Engineering Department at KAIST. Doctor Kitchen supplies precooked food, which helps diabetic patients regulate their diet. The company offers a personalized diet plan to customers so that they can effectively manage their disease and monitor their blood sugar level efficiently.
The Chief Executive Officer of Mirae Holdings, Young-Ho Kim, said, “We can assist KAIST researchers who aspire to create a company based on their research outcomes through various stages of startup services such as making business plans, securing venture capitals, and networking with existing businesses.”
Young-Ho Kim (left in the picture), the Chief Executive Officer of Mirae Holdings, holds a certificate of company registration with Sang-Min Oh (right in the picture), the Chief Executive Officer of Cresem.
Young-Ho Kim (left in the picture), the Chief Executive Officer of Mirae Holdings, holds a certificate of company registration with Jae-Yeun Park (right in the picture), the Chief Executive Officer of Dr. Kitchen.
2015.07.29 View 10959 -
KVIP Opened in Pangyo
KAIST has opened the KAIST Venture Innovation Program (KVIP) in its Center for Industry Outreach, designed for executive and high-ranking officers of venture companies. Located in Pangyo Techno Valley, KAIST’s Center for Industry Outreach was established in collaboration with the government of Gyeonggi Province to support venture companies in Pangyo for business management training, venture networking, and university-industry cooperation.
The program will be held every Monday for 12 weeks from April 13 to July 6 in KAIST’s Center for Industry Outreach. This executive education program mainly focuses on solving problems that arise when a medium-sized venture company is in the course of growing into a global corporation. The program is divided into four courses which will cover business management, competition in the global market, transformation of a company, and technological innovation.
Professors from various departments at KAIST will give lectures on their fields. Professor Jaeseung Jeong from the Bio and Brain Engineering Department, Professor Hoi-Jun Yoo from the Electrical Engineering Department, Professor Sangmin Bae from the Industrial Design Department, and Professor Kwangjae Sung from the Business and Technology Management Department will each deliver lectures on brain engineering, semiconductor, design, and restructuring.
Industry experts are also invited to give talks, including Dr. Dae-Gyu Byun, the Chief Executive Officer and President of HUMAX Electronics, Dr. Gwang-Cheol Choi, the Chief Executive Officer of SK Engineering & Construction, Mr. Il-young Kim, the former Chief Executive Officer of KT, Dr. Jae-hoon Jeong, the President of the Korea Institute for the Advancement of Technology (KIAT), Dr. Intak Bae, the Chief Executive Officer of Summit Partners, and Mr. Kyung-taek Kwak, a film director.
The department has started recruiting first round applicants for the program, targeting executive and high-ranking officers of middle-sized venture companies. The details of the program can be found on its website, kvip.kaist.ac.kr.
2015.03.23 View 9495 -
Board Chairman Chung Makes First Visit to Building Named After Him
Moon-Soul Chung, chairman of the KAIST board of trustees, visited the building built with his donation on Monday (Oct. 19) for the first time since he made the deed of gift eight years ago, university authorities said on Monday (Oct. 19).
In 2000, Chung, founder and former CEO of Mirae Corp, manufacturer of semiconductor testing equipment, announced retirement and handed over the presidency of his company to one of his managing directors. One year later in 2001, he donated 30 billion won, then equivalent to $30 million, to KAIST. It was by then the largest amount given by a single donor.
The major part of his donation went to constructing a building for the newly-established Department of Bio and Brain Engineering, and it was named after him. However, Chung did not attend the ground-breaking and dedication ceremonies, saying that he would not enter the building until KAIST achieved a breakthrough technology which can inject a hope to Koreans.
On his first visit to the building, he was briefed on the major research outcomes of the department over the past seven years, which were highlighted by the recent invention of an apparatus for measuring perfusion rate of legs. A KAIST team headed by Prof. Chul-Hee Choi invented a light leakage prevention unit including a light emitting device for radiating light having a certain wavelength onto a living body injected with Indocyanine Green (ICG).
According to Prof. Choi, the invention relates to an apparatus for measuring the perfusion rate of legs. The invention also includes a light leakage prevention housing formed to prevent transmission of external light.
Chung expressing satisfaction with the achievements and encouraged professors, researchers and students working at the Moon-Soul Chung Building.
2009.10.20 View 12867