Science
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KAIST and KOICA Invited Dominican Republic Officials for Workshop
KAIST will host a two-week workshop for Dominican Republic officials and scholars in collaboration with KOICA (Korea International Cooperation Agency) beginning October 23 at KAIST.
The workshop aims to encourage academia-industry cooperation as one of the Projects for Human Resource Development for Science and Technology at KOICA. Dominican participants including the assistant minister of the Ministry of Higher Education, Science and Technology (MESCYT) and deans of engineering colleges at major universities will enjoy lectures from experts and visit enterprises known for excellent academia-industry collaboration.
According to the Center for Overseas Development, at which Professor WonJoon Kim in the School of Business and Technology Management at KAIST holds the position of director, the workshop is designed to develop human resources in the science and technology (S&T) area, share knowledge on research and development in the field of academia-industry cooperation, and help the participants acquire know-how for managing partnerships between related organizations and industries.
During the workshop, KAIST plans to transfer know-how and share knowledge on its academia-industry cooperation R&D system, in hopes that the workshop will help the Dominican Republic foster its manpower in higher education. The workshop organizers hope that the officers and scholars will be able to apply what they will learn for establishing and carrying out detailed action plans for academia-industry cooperation policies in an effective manner.
“This workshop provides an opportunity to learn about the development of S&T in Korea, academia-industry cooperation R&D, and fostering manpower in advanced S&T. Through the knowledge sharing, we can have a better understanding of academia-industry cooperation as well as education on advanced manpower,” said Pedro Antonio Eduardo, the assistant minister of MESCYT.
He added, “I hope that this workshop will further detailed cooperation between the two countries for Korean high-tech enterprises’ overseas expansion and advanced manpower education. The development model in Korea has many essential elements, so learning its engine for growth and polytechnic manpower education will help develop my country’s industry sector.”
The Project for Human Resource Development for Science and Technology is one of the official development assistance projects running from last year until 2019. It promotes R&D activities for S&T in the Dominican Republic, encouraging academia-industry cooperation by improving trainers in charge of advanced manpower education.
2017.10.30 View 8722 -
Distinguished Professor Lee Named International Fellow of the CAS
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering at KAIST was awarded the title of distinguished professor and international fellow from the Chinese Academy of Sciences (CAS), and honorary professor from its affiliated organization the Tianjin Institute of Industrial Biotechnology (TIB).
The CAS recognized Distinguished Professor Lee for his significant contributions to biotechnology. He has made significant pioneering academic achievements in the area of systems metabolic engineering, which produces useful chemicals from microorganisms. Not only did he develop the first and best source technology in that field, but also came out with processes for the production of biofuel and environmentally-friendly chemicals.”
As a global leader in systems metabolic engineering, Distinguished Professor Lee has also been appointed as an honorary professor at Jiangnan University in Wuxi, China.
Distinguished Professor Lee was listed in the ‘Top 20 Translational Researchers of 2014’ selected by the renowned international journal Nature Biotechnology. Moreover, he was the first Asian recipient of the James E. Bailey Award in 2016 and Marvin J. Johnson Award in 2012, which are given to scholars in the field of biotechnology.
He is also one of 13 global scientists who are foreign members of the renowned academic societies the National Academy of Engineering and the National Academy of Sciences in the US. Furthermore, he received the ‘2017 Korea Best Scientist Award’ from the president of Korea in July. Finally, his founding field, systems metabolic engineering, was chosen as one of the ‘Top 10 Emerging Technologies of 2016’ by the World Economic Forum.
The Chinese Academy of Sciences, established in November 1949, is an academic organization that carries out research on basic sciences and natural sciences in China. It defined its science and technology system to include the fields of basic sciences, natural sciences, and high technology. While having a base in Beijing, its branch academies are located in 12 main cities along with 117 affiliates and 100 national key labs.
2017.10.26 View 12660 -
Development of a Highly-Accurate Computational Model of Human Metabolism
A research team from KAIST developed a computational framework that enables the reconstruction of a comprehensive computational model of human metabolism, which allows for an accurate prediction of personal metabolic features (or phenotypes).
Understanding personal metabolic phenotypes allows us to design effective therapeutic strategies for various chronic and infectious diseases. A human computational model called the genome-scale metabolic model (GEM) contains information on thousands of metabolic genes and their corresponding reactions and metabolites, and has played an important role in predicting metabolic phenotypes. Although several versions of human GEMs have been released, they had room for further development, especially as to incorporating biological information coming from a human genetics mechanism called “alternative splicing.” Alternative splicing is a genetic mechanism that allows a gene to give rise to multiple reactions, and is strongly associated with pathology.
To tackle this problem, Jae Yong Ryu (a Ph.D. student), Dr. Hyun Uk Kim (Research Fellow), and Distinguished Professor Sang Yup Lee, all from the Department of Chemical and Biomolecular Engineering at KAIST, developed a computational framework that systematically generates metabolic reactions, and adds them to the human GEM. The resulting human GEM was demonstrated to accurately predict metabolic phenotypes under varied environmental conditions. The research results were published online in Proceedings of the National Academy of Sciences (PNAS) on October 24, 2017, under the title “Framework and resource for more than 11,000 gene-transcript-protein-reaction associations in human metabolism.”
The research team first updated the biological contents of a previous version of the human GEM. The updated biological contents include metabolic genes and their corresponding metabolites and reactions. In particular, metabolic reactions catalyzed by already-known protein isoforms were additionally incorporated into the human GEM; protein isoforms are multiple variants of proteins generated from individual genes through the alternative splicing process. Each protein isoform is often responsible for the operation of a metabolic reaction. Although multiple protein isoforms generated from one gene can play different functions by having different sets of protein domains and/or subcellular localizations, such information was not properly considered in previous versions of human GEMs.
Upon the initial update of the human GEM, named Recon 2M.1, the research team subsequently implemented a computational framework that systematically generates information on Gene-Transcript-Protein-Reaction Associations (GeTPRA) in order to identify protein isoforms that were previously not identified. This framework was developed in this study. As a result of the implementation of the framework for GeTPRA, more than 11,000 GeTPRA were automatically predicted, and thoroughly validated. Additional metabolic reactions were then added to Recon 2M.1 based on the predicted GeTPRA for the previously uncharacterized protein isoforms; Recon 2M.1 was renamed Recon 2M.2 from this upgrade.
Finally, Recon 2M.2 was integrated with 446 sets of personal biological data (RNA-Seq data) in order to build patient-specific cancer models. These patient-specific cancer models were used to predict cancer metabolism activities and anticancer targets.
The development of a new version of human GEMs along with the computational framework for GeTPRA is expected to boost studies in fundamental human genetics and medicine. Model files of the human GEMs Recon 2M.1 and 2M.2, a full list of the GeTPRA and the source code for the computational framework to predict the GeTPRA are all available as part of the publication of this study.
Distinguished Professor Lee said, “The predicted GeTPRA from the computational framework is expected to serve as a guideline for future experiments on human genetics and biochemistry, whereas the resulting Recon 2M.2 can be used to predict drug targets for various human diseases.”
This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557) from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.
(Figure 1:A scheme of Recon 2M.1 development and its use in reconstructing personal genome-scale metabolic models (GEMs). (A) A concept of alternative splicing of human genes and its use in Gene-Transcript-Protein-Reaction Associations (GeTPRA) of Recon 2M.1. (B) A procedure of systematic refinement of the Recon 2Q. Recon 2Q is one of the previously released human GEMs. Biochemically inconsistent reactions include unbalanced, artificial, blocked, and/or redundant reactions. Iterative manual curation was conducted while validating the Recon 2M.1. (C) Reconstruction of cancer patient-specific GEMs using Recon 2M.1 for further simulation studies. In this study, personal biological data (RNA-Seq data) were obtained from The Cancer Genome Atlas (TCGA; https://cancergenome.nih.gov/ ) across the ten cancer types.
(Figure 2: Computational framework for the systematic generation of Gene-Transcript-Protein-Reaction Associations (GeTPRA; red box in the flowchart). Peptide sequences of metabolic genes defined in Recon 2M.1 were retrieved from a database called Ensembl. EC numbers and subcellular localizations of all the protein isoforms of metabolic genes in Recon 2M.1 were predicted using software programs EFICAz2.5 and Wolf PSort, respectively. Information on the newly predicted GeTPRA was systematically incorporated into the Recon 2M.1, thereby resulting in Recon 2M.2.)
2017.10.25 View 10639 -
Postech-KAIST Rivalry Heats Up at the 16th Science War
The 16th Postech-KAIST Science War wrapped up its two-day rivals’ duel at the KAIST campus in Daejeon on September 23. The event was established in 2002 to build a close tie between the two renowned universities for science and technology, and to provide students with an opportunity to demonstrate their talents and abilities.
On September 21, a convoy of red Postech buses carrying more than 650 athletes, students, and supporters arrived at the KAIST campus in Daejeon. The two teams competed in eight events including both online and sports event.
The night before the actual games started, cheerleading teams from both Postech Cheero and KAIST ELKA kicked off the event.
1st Day (September 22)
The hacking tournament marked the beginning of the Science War. The event started at nine in the morning. Both teams had to solve four problems within 12 hours.
While the fierce hacking competition was underway, school music bands, including Twenties Dreams, opened up the event with beautiful voices.
The soccer game took place in the university stadium. The KAIST soccer team brought the first win to KAIST, and was their second straight victory in soccer.
At the outdoor theatre, the evening games, including Artificial Intelligence and E-sports (League of Legend) began. After the E-sports, both KAIST’s and Postech’s music and dance clubs showed amazing performances adding more excitement to the event.
Another fun aspect of the event was the ‘evening street food market’. Food trucks and food booths were lined up to satisfy students’ hunger. Talso here were various game booths such as can bowling, balloon darts, and lamp DIY.
2nd Day (September 23)
The baseball team marked the second day of the Science War in the Undergraduate Field. The KAIST team won the game by six runs.
Science quizzes sealed the Postech-KAIST Science War. Although the KAIST team led at the beginning, the Postech team overtook them by getting bonus point answers correct. This game decided Postech winning this year’s Science War.
As a spin-off, a badminton game was held in the Sports Complex and the KAIST team beat the Postech team with ease.
Last but not least, a basketball game was held in the Sports Complex. In the last game of the Science War, the KAIST team wiped away the stain of last year’s defeat.
At the closing ceremony, famous rappers and school music clubs celebrated the last moments of the Science War.
(Jiwon Hwang, Public Relations of the 16th Science War Committee)
(The 16th Science War Committee)
Cheers to the students committees, participants, and supporters who put every ounce of their effort into successfully running the 16th Postech-KAIST Science War.
Day
Category
Winner
Day 1
Hacking
Postech
Soccer
KAIST
Artificial Intelligence
Postech
E-Sports (LoL)
Postech
Day 2
Baseball
KAIST
Science Quizzes
Postech
Badminton (spin-off)
KAIST
Basketball
KAIST
(The final tally for KAIST in the Science Wars was eight wins and six losses)
2017.09.27 View 6665 -
Semiconductor Patterning of Seven Nanometers Technology Using a Camera Flash
A research team led by Professor Sang Ouk Kim in the Department of Materials Science and Engineering at KAIST has developed semiconductor manufacturing technology using a camera flash.
This technology can manufacture ultra-fine patterns over a large area by irradiating a single flash with a seven-nanometer patterning technique for semiconductors. It can facilitate the manufacturing of highly efficient, integrated semiconductor devices in the future.
Technology for the Artificial Intelligence (AI), the Internet of Things (IoTs), and big data, which are the major keys for the fourth Industrial Revolution, require high-capacity, high-performance semiconductor devices. It is necessary to develop lithography technology to produce such next-generation, highly integrated semiconductor devices.
Although related industries have been using conventional photolithography for small patterns, this technique has limitations for forming a pattern of sub-10 nm patterns.
Molecular assembly patterning technology using polymers has been in the spotlight as the next generation technology to replace photolithography because it is inexpensive to produce and can easily form sub-10 nm patterns. However, since it generally takes a long time for heat treatment at high-temperature or toxic solvent vapor treatment, mass production is difficult and thus its commercialization has been limited.
The research team introduced a camera flash that instantly emits strong light to solve the issues of polymer molecular assembly patterning. Using a flash can possibly achieve a semiconductor patterning of seven nanometers within 15 milliseconds (1 millisecond = 1/1,000 second), which can generate a temperature of several hundred degrees Celsius in several tens of milliseconds.
The team has demonstrated that applying this technology to polymer molecular assembly allows a single flash of light to form molecular assembly patterns.
The team also identified its compatibility with polymer flexible substrates, which are impossible to process at high temperatures. Through these findings, the technology can be applied to the fabrication of next-generation, flexible semiconductors.
The researchers said the camera flash photo-thermal process will be introduced into molecular assembly technology and this highly-efficiency technology can accelerate the realization of molecular assembly semiconductor technology.
Professor Kim, who led the research, said, “Despite its potential, molecular assembly semiconductor technology has remained a big challenge in improving process efficiency.” “This technology will be a breakthrough for the practical use of molecular assembly-based semiconductors.”
The paper was published in the international journal, Advanced Materials on August 21 with first authors, researcher Hyeong Min Jin and PhD candidate Dae Yong Park.
The research, sponsored by the Ministry of Science and ICT, was co-led Professor by Keon Jae Lee in the Department of Materials Science and Engineering at KAIST, and Professor Kwang Ho Kim in the School of Materials Science and Engineering at Pusan National University.
(1. Formation of semiconductor patterns using a camera flash)
(Schematic diagram of molecular assembly pattern using a camera flash)
(Self-assembled patterns)
2017.09.18 View 11938 -
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 9903 -
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 10007 -
Discovery of an Optimal Drug Combination: Overcoming Resistance to Targeted Drugs for Liver Cancer
A KAIST research team presented a novel method for improving medication treatment for liver cancer using Systems Biology, combining research from information technology and the life sciences. Professor Kwang-Hyun Cho in the Department of Bio and Brain Engineering at KAIST conducted the research in collaboration with Professor Jung-Hwan Yoon in the Department of Internal Medicine at Seoul National University Hospital. This research was published in Hepatology in September 2017 (available online from August 24, 2017).
Liver cancer is the fifth and seventh most common cancer found in men and women throughout the world, which places it second in the cause of cancer deaths. In particular, Korea has 28.4 deaths from liver cancer per 100,000 persons, the highest death rate among OECD countries and twice that of Japan.
Each year in Korea, 16,000 people get liver cancer on average, yet the five-year survival rate stands below 12%. According to the National Cancer Information Center, lung cancer (17,399) took the highest portion of cancer-related deaths, followed by liver cancer (11,311) based on last year data.
Liver cancer is known to carry the highest social cost in comparison to other cancers and it causes the highest fatality in earlier age groups (40s-50s). In that sense, it is necessary to develop a new treatment that mitigates side effects yet elevates the survival rate.
There are ways in which liver cancer can be cured, such as surgery, embolization, and medication treatments; however, the options become limited for curing progressive cancer, a stage in which surgical methods cannot be executed.
Among anticancer medications, Sorafenib, a drug known for enhancing the survival rate of cancer patients, is a unique drug allowed for use as a targeted anticancer medication for progressive liver cancer patients. Its sales reached more than ten billion KRW annually in Korea, but its efficacy works on only about 20% of the treated patients. Also, acquired resistance to Sorafenib is emerging. Additionally, the action mechanism and resistance mechanism of Sorafenib is only vaguely identified.Although Sorafenib only extends the survival rate of terminal cancer patients less than three months on average, it is widely being used because drugs developed by global pharmaceutical companies failed to outperform its effectiveness.
Professor Cho’s research team analyzed the expression changes of genes in cell lines in response to Sorafenib in order to identify the effect and the resistance mechanism of Sorafenib.
As a result, the team discovered the resistance mechanism of Sorafenib using Systems Biology analysis. By combining computer simulations and biological experiments, it was revealed that protein disulfide isomerase (PDI) plays a crucial role in the resistance mechanism of Sorafenib and that its efficacy can be improved significantly by blocking PDI.
The research team used mice in the experiment and discovered the synergic effect of PDI inhibition with Sorafenib for reducing liver cancer cells, known as hepatocellular carcinoma. Also, more PDIs are shown in tissue from patients who possess a resistance to Sorafenib. From these findings, the team could identify the possibility of its clinical applications. The team also confirmed these findings from clinical data through a retrospective cohort study.
“Molecules that play an important role in cell lines are mostly put under complex regulation. For this reason, the existing biological research has a fundamental limitations for discovering its underlying principles,” Professor Cho said. “This research is a representative case of overcoming this limitation of traditional life science research by using a Systems Biology approach, combining IT and life science. It suggests the possibility of developing a new method that overcomes drug resistance with a network analysis of the targeted drug action mechanism of cancer.”
The research was supported by the National Research Foundation of Korea (NRF) and funded by the Ministry of Science and ICT.
(Figure 1. Simulation results from cellular experiments using hepatocellular carcinoma)
(Figure 2. Network analysis and computer simulation by using the endoplasmic reticulum (ER) stress network)
(Figure 3. ER stress network model)
2017.08.30 View 12649 -
Professor Dan Keun Sung Endows Scholarship in Honor of His Retirement
Professor Dan Keun Sung in the School of Electrical Engineering contributed a 100 million KRW scholarship fund this month to KAIST to mark his retirement after more than three decades of work.
“As my retirement date comes closer, I have been thinking about what I could do for the school. I wanted to leave something behind, even though it’s small, for my lifelong school and students. I am hoping that this scholarship fund will benefit the members of KAIST.”
This isn’t his first time making a donation to KAIST. In 2013, Professor Sung donated ten million KRW, which was his cash prize from the 9th Haedong Academic Award of The Korean Institute of Communications and Information Sciences (KICS). At that time, Professor Sung had the chance to create a scholarship fund in his name; however, he wanted to highlight that the scholarship fund was for ‘someone,’ not created by ‘someone.’ In that sense, his scholarship fund was created with no name to benefit students in the School of Electrical Engineering. His colleagues and students supported his idea. Professor Seonghwan Cho, students, and alumni also participated in fund raising efforts, which reached 55 million KRW in total.
Professor Sung emphasized, “Donations should always be remembered, no matter how small they are.” He then explained his purpose for creating the scholarship fund by saying, “Fundraising can be truly meaningful to contributors, knowing that their money is going to supporting the school and students.”
Professor Sung, a fellow of the Institute of Electrical and Electronics Engineers (IEEE) Communication Society, started his post at KAIST in 1986. For the past 30 years, he has devoted himself to fostering young scholars and studying in the area of information and communication. He also participated in developing technologies for the resource management of various future cellular components, such as satellites, switchboards, and signaling networks.
2017.08.11 View 10154 -
Analysis of Gas Adsorption Properties for Amorphous Porous Materials
Professor Jihan Kim from the Department of Chemical and Biomolecular Engineering at KAIST has developed a method to predict gas adsorption properties of amorphous porous materials.
Metal-organic frameworks (MOFs) have large surface area and high density of pores, making them appropriate for various energy and environmental-related applications. And although most MOFs are crystalline, these structures can deform during synthesis and/or industrial processes, leading to loss in long-range order. Unfortunately, without the structural information, existing computer simulation techniques cannot be used to model these materials.
In this research, Professor Kim’s research team demonstrated that one can replace the material properties of structurally deformed MOFs with those of crystalline MOFs to indirectly analyze/model the material properties of amorphous materials. First, the team conducted simulations on methane gas adsorption properties for over 12,000 crystalline MOFs to obtain a large training set data, and created a resulting structure-property map. Upon mapping the experimental data of amorphous MOFs onto the structure-property map, results showed that regardless of crystallinity, the gas adsorption properties of MOFs showed congruence and consistency amongst one another.
Based on these findings, selected crystalline MOFs with the most similar gas adsorption properties as the collapsed structure from the 12,000 candidates. Then, the team verified that the adsorption properties of these similar MOFs can be successfully transferred to the deformed MOFs across different temperatures and even to different gas molecules (e.g. hydrogen), demonstrating transferability of properties.
These findings allow material property prediction in porous materials such as MOFs without structural information, and the techniques here can be used to better predict and understand optimal materials for various applications including, carbon dioxide capture, gas storage and separations.
This research was conducted in collaboration with Professor Dae-Woon Lim at Kyoto University, Professor Myunghyun Paik at Seoul National University, Professor Minyoung Yoon at Gachon University, and Aadesh Harale at Saudi Arabian Oil Company. The research was published in the Proceedings of the National Academy of Sciences (PNAS) online on 10 July and the co-first authors were Ph. D. candidate WooSeok Jeong and Professor Dae-Woon Lim.
This research was funded by the Saudi Aramco-KAIST CO2 Management Center.
(Figure 1. Trends in structure - material property map and in collapsed structures)
(Figure 2. Transferability between the experimental results of collapsed MOFs and the simulation results of crystalline MOFs)
2017.07.26 View 10293 -
Structural Insights into the Modulation of Synaptic Adhesion by MDGA for Synaptogenesis
Synapses connected by various synaptic adhesion molecules are communication spaces between neurons for transmitting information. Among various synaptic adhesion molecules, neuroligins are arguably the most widely studied class of postsynaptic adhesion molecules, which mainly interact with presynaptic neurexins to induce excitatory or inhibitory synapse development. Recently, the membrane-associated mucin (MAM) domain-containing GPI anchor protein 1 (MDGA1) has been characterized as a key suppressor of Neuroligin-2/Neurexin-1β-mediated inhibitory synapse development, but how it acts remains a mystery.
In a recent issue of Neuron, published on June 21, 2017, a research team led by Professor Ho Min Kim at the Graduate School of Medical Science and Engineering of KAIST reported the three-dimensional structure of MDGA1/Neuroligin-2 complex and mechanistic insights into how MDGAs negatively modulate synapse development governed by Neurexins/Neuroligins trans -synaptic adhesion complex.
MDGA1 consists of six Ig-like domains, fibronectin type III repeat domain, and MAM domain . The crystal structure of MDGA1/Neuroligin-2 complex reveals that they form the 2:2 hetero-tetrameric complex and only the Ig1-Ig2 domains of MDGA1 are involved in interactions with Neuroligin-2. The structural comparison between the MDGA1/Neuroligin-2 and Neurexin-1β/Neuroligin-1 complexes intriguingly indicates that the Neuroligin-2 region binding to MDGA1 largely overlaps with that of Neurexin-1β, but the interaction interface of the MDGA1/Neuroligin-2 complex is much larger than that of the Neurexin-1β/Neuroligin-1 complex. This explains why Neuroligin-2 binds stronger to MDGA1 than Neurexin-1β, and how the favored MDGA1 binding to Neuroligin-2 sterically blocks the interaction between Neuroligin-2 and Neurexin-1β, which is critical for the suppression of inhibitory synapse development.
“Although we found that MDGA Ig domains (Ig 1 and Ig 2) are sufficient to form a complex with NL2, other extracellular domains, including Ig 3–6, FN III, and MAM domains, may also contribute to stable cis-interactions between MDGA1 and Neuroligin-2 by providing conformational flexibility. Therefore, further structural analysis of full-length MDGA will be required,” Professor Kim said.
Neuroligin-2 specifically promotes the development of inhibitory synapses, whereas neuroligin-1 promotes the development of excitatory synapses. Recently, not only MDGA1, but also MDGA2 have emerged as synaptic regulators for the development of excitatory or inhibitory synapses. In vitro biochemical analysis in this research clearly demonstrates that Neuroligin-1 and Neuroligin-2 bind to both MDGA1 and MDGA2 with comparable affinity. However, pull-down assays using detergent-solubilized mouse brain membrane fractions show the specific interaction of MDGA1 with Neuroligin-2, but not with Neuroligin-1. “This suggests that unidentified processes may dictate the selective association of MDGA1 with Neuroligin-2 in vivo , ” explained Professor Jaewon Ko at the Daegu Gyeongbuk Institute of Science and Technology (DGIST).
A balance between excitatory and inhibitory synapses is crucial to healthy cognition and behavior. Mutations in neuroligins, neurexins, and MDGAs, which can disrupt the excitatory/inhibitory balance, are associated with neuropsychiatric diseases such as autism and schizophrenia. Jung A Kim at KAIST, first author in this study, said, “Our discovery from integrative investigations are an important first step both for a better understanding of Neuroligin/Neurexin synaptic adhesion pathways and MDGA-mediated regulation of synapse development as well as the development of potential new therapies for autism, schizophrenia, and epilepsy.”
2017.07.10 View 9454 -
Cooperative Tumor Cell Membrane-Targeted Phototherapy
A KAIST research team led by Professor Ji-Ho Park in the Bio and Brain Engineering Department at KAIST developed a technology for the effective treatment of cancer by delivering synthetic receptors throughout tumor tissue. The study, led by Ph.D. candidate Heegon Kim, was published online in Nature Communications on June 19.
Cancer targeted therapy generally refers to therapy targeting specific molecules that are involved in the growth and generation of cancer. The targeted delivery of therapeutics using targeting agents such as antibodies or nanomaterials has improved the precision and safety of cancer therapy.
However, the paucity and heterogeneity of identified molecular targets within tumors have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes.
To solve this problem, the team constructed a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumor cell membrane-selective localization of synthetic receptors to amplify the subsequent targeting of therapeutics. Here, synthetic and biological nanocomponents refer to liposomes and extracellular vesicles, respectively.
The synthetic receptors are first delivered selectively to tumor cell membranes in the perivascular region using liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the synthetic receptors are transferred to neighboring cells and further spread throughout the tumor tissues where the molecular targets are limited.
Hitchhiking extracellular vesicles for delivery of synthetic receptors was possible since extracellular vesicles, such as exosomes, mediate intercellular communications by transferring various biological components such as lipids, cytosolic proteins, and RNA through a membrane fusion process. They also play a supportive role in promoting tumor progression in that tumor-derived extracellular vesicles deliver oncogenic signals to normal host cells.
The team showed that this tumor cell membrane-targeted delivery of synthetic receptors led to a uniform distribution of synthetic receptors throughout a tumor and subsequently led to enhanced phototherapeutic efficacy of the targeted photosensitizer.
Professor Park said, “The cooperative tumor targeting system is expected to be applied in treating various diseases that are hard to target.”
The research was funded by the Basic Science Research Program through the National Research Foundation funded by the Ministry of Science, ICT & Future Planning, and the National R&D Program for Cancer Control funded by the Ministry for Health and Welfare.
(Ph.D. candidates Hee Gon Kim (left) and Chanhee Oh)
Figure 1. A schematic of a cooperative tumor targeting system via delivery of synthetic receptors.
Figure 2. A confocal microscopic image of a tumor section after cooperative targeting by synthetic receptor delivery. Green and magenta represent vessels and therapeutic agents inside a tumor respectively.
2017.07.07 View 11697