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President Shin Presents Opportunities & Challenges of the 4IR at the Summer Davos Forum
(President Shin makes a keynote speech at the 2018 Summer Davos Forum in China on Sept.20.)
KAIST co-hosted the Asia Session with the World Economic Forum during the 2018 Summer Davos Forum in Tianjin, China from September 18 through 20. The session highlighted regional collaboration in Asia to promote inclusive growth in the Fourth Industrial Revolution.
KAIST is working closely with the WEF to take the lead in the Fourth Industrial Revolution. Last July, KAIST established the Fourth Industrial Revolution Information Center (FIRIC) at the KAIST Institute and signed an MOU with the Center for the Fourth Industrial Revolution (C4IR) at the WEF in October. The session is a follow-up event KAIST and the C4IR agreed to last year during the Roundtable Session held in Seoul.
Many experts in new emerging industries as well as many project directors, including Director Murat Sonmez of the C4IR, attended the session KAIST hosted. Director Chizuru Suga at the C4IR in Japan, Director Danil Kerimi in China, and Director Shailesh Sharda in India also attended the session and discussed ways to expand collaboration and networks among the countries.
In his keynote speech at the session on September 20, President Sung-Chul Shin presented how the Korean government is trying to drive the economy by strategically investing in focused industries in the new global industrial environment. President Shin introduced the government’s strategic roadmap to build the competitiveness of emerging technologies such as AI, blockchain, and precision medicine.
He also stressed that the three components of innovation, collaboration, and speed should be prioritized in all sectors for the successful realization of the Fourth Industrial Revolution. For instance, innovation in education, research, and technology commercialization, expansive domestic and international collaboration beyond the private and public sectors, speedy deregulation, and efficient governance will all be critical.
He also said that KAIST will launch new pilot collaboration projects along with the WEF soon. “We paved the way for leading the network with major countries including Japan and India for advancing the Fourth Industrial Revolution through this session,” President Shin said.
2018.09.21 View 10014 -
Effective Drug Delivery to Heart with Tannic Acid
(Professor Haeshin Lee from the Department of Chemistry) Typical methods of drug delivery to the heart require surgical procedures involving incisions in the chest wall and bones. To efficiently treat cardiovascular and related vascular diseases without surgery, a KAIST research team developed a heart-targeting drug delivery technology using tannin acid via intravenous systemic injection. This method can be applied to the development of a variety of new protein-based drugs.
Cardiovascular-circulatory disease is currently the second leading cause of death in Korea. A typical example of this disease is myocardial infarction caused by poor oxygen and nutrient supply due to narrowed coronary arteries and poor blood flow to the heart.
Although there have been numerous research projects to develop chemotherapeutic drugs and therapeutic proteins, clinics still rely on surgical procedures. Drug delivery can be an alternative, but it is quite challenging because ceaseless dynamic cycles of the heart and massive exchanges of blood mean administered therapeutics do not stay inside the heart very long.
Professor Haeshin Lee from the Department of Chemistry and his team employed tannic acid (TA), which is known for giving bitter taste to wines. It is one of the most abundant polyphenols and can be easily found in plants, such as fruits, vegetables, cacao, and others. TA has also been used as a multifunctional coating molecule.
Using these properties of TA, the team complexed protein and peptide therapeutics with tannic acid and succeeded in targeting protein and peptide therapeutics to the heart. TA, coated on the surface of a granulated protein complex, helps maintain cardiac function because it adheres to extracellular matrices, elastin, and collagens in heart tissues allowing the protein to stay attached to the heart tissue for a longer period.
The team confirmed that these Tannic-acid-modified proteins stay in blood vessels five days longer than with protein-only injections. Additionally they found that TA-protein complexes do not show any cardiac toxicity and do not cause noticeable pathology.
The team has been continuously developing biomaterials for medical applications by testing various polyphenolic materials that feature adhesive and coating properties, including tannic acid. They have injected a mixture of TA and fibroblast growth factors (FGF) into animal models with myocardial infarctions. After four weeks, they confirmed that the infarction was reduced and the left ventricular pressure and cardiac output were almost normalized.
Professor Lee said, “Although there have been numerous drugs related to heart disease, so far there has not been efficient drug delivery to the heart so this technology will be able to reformulate existing drugs into new and more efficient drugs.”
This research, jointly led by Dr. Ki-Suk Kim from the Predictive Model Research Center, was published in Nature Biomedical Engineering on April 30 ( http://www.nature.com/articles/s41551-018-0227-9 ).
Figure 1. Schematic for the heart-targeting mechanism of TANNylated protein nanocomplexes: (1) size-dependent permeation, (2) phenolic (that is, TA), and (3) internalization by internalization by myoblasts
Figure 2. Effect of TA based protein complexes on cardiac cell transport efficiency and viral gene expression efficiency and therapeutic function in animal models with myocardial infarction
2018.09.18 View 6185 -
Engineered E. coli Using Formic Acid and CO2 As a C1-Refinery Platform Strain
(Figure: Formic acid and CO2 assimilation pathways consisting of the reconstructed THF cycle and reverse glycine cleavage reaction. This schematic diagram shows the formic acid and CO2 assimilation procedure through the pathway. Plasmids used in this study and the genetic engineering performed in this study are illustrated.)
A research group at KAIST has developed an engineered E. coli strain that converts formic acid and CO2 to pyruvate and produces cellular energy from formic acid through reconstructed one-carbon pathways. The strategy described in this study provides a new platform for producing value-added chemicals from one-carbon sources.
Formic acid is a carboxylic acid composed of one carbon. Formic acid was produced from CO2 by the chemical method. Recently, the C1 Gas Refinery R&D Center has successfully developed a biological process that produces formic acid from carbon monoxide for the first time. Formic acid is in a liquid state when at room temperature and atmospheric pressure. In addition, it is chemically stable and less toxic, thus, easy to store and transport. Therefore, it can be used as an alternative carbon source in the microbial fermentation process. In order to produce value-added chemicals using formic acid, a metabolic pathway that converts formic acid into cellular molecules composed of multiple carbons is required. However, a metabolic pathway that can efficiently convert formic acid into cellular molecules has not been developed. This acted as an obstacle for the production of value-added chemicals using formic acid
A research group of Ph.D. student Junho Bang and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. This study, entitled “Assimilation of Formic Acid and CO2 by Engineered Escherichia coli Equipped with Reconstructed One-Carbon Assimilation Pathways”, has been published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on September 18.
There has been increasing interest in utilizing formic acid as an alternative carbon source for the production of value-added chemicals. This research reports the development of an engineered E. coli strain that can convert formic acid and CO2 to pyruvate and produce cellular energy from formic acid through the reconstructed one-carbon pathways.
The metabolic pathway that efficiently converts formic acid and CO2 into pyruvate was constructed by the combined use of the tetrahydrofolate cycle and reverse glycine cleavage reaction. The tetrahydrofolate cycle was reconstructed by utilizing Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase. The glycine cleavage reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes that encode enzymes related with the glycine cleavage reaction. Formic acid and CO2 conversion to pyruvate was increased via metabolic engineering of the E. coli strain equipped with the one-carbon assimilation pathway.
In addition, in order to reduce glucose consumption and increase formic acid consumption, Candida boidnii formate dehydrogenase was additionally introduced to construct a cellular energy producing pathway from formic acid. This reduces glucose consumption and increases formic acid consumption.
The reconstructed one-carbon pathways can supply cellular molecules and cellular energies from the formic acid and CO2. Thus, the engineered E. coli strain equipped with the formic acid and CO2 assimilation pathway and cellular energy producing pathway from formic acid showed cell growth from formic acid and CO2 without glucose. Cell growth was monitored and 13C isotope analysis was performed to confirm E. coli growth from the formic acid and CO2. It was found that the engineered E. coli strain sustained cell growth from the formic acid and CO2 without glucose.
Professor Lee said, “To construct the C1-refinery system, a platform strain that can convert one-carbon materials to higher carbon materials needs to be developed. In this report, a one-carbon pathway that can efficiently convert formic acid and CO2 to pyruvate was developed and a cellular energy producing pathway from formic acid was introduced. This resulted in an engineered E. coli strain that can efficiently utilize formic acid as a carbon source while glucose consumption was reduced. The reconstructed one-carbon pathways in this research will be useful for the construction of the C1-refinery system.”
This work was supported by the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016M3D3A1A01913250). For further information: Sang Yup Lee, Distinguished Professor of Chemical and Biomolecular Engineering, KAIST (leesy@kaist.ac.kr, Tel: +82-42-350-3930)
2018.09.18 View 7885 -
Distinguished Professor Sang Yup Lee Announced as the Eni Award Recipient
(Distinguished Professor Sang Yup Lee)
Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering will be awarded the 2018 Eni Advanced Environmental Solutions Prize in recognition of his innovations in the fields of energy and environment. The award ceremony will take place at the Quirinal Palace, the official residence of Italian President Sergio Mattarella, who will also be attending on October 22.
Eni, an Italian multinational energy corporation established the Eni Award in 2008 to promote technological and research innovation of efficient and sustainable energy resources. The Advanced Environmental Solutions Prize is one of the three categories of the Eni Award. The other two categories are Energy Transition and Energy Frontiers. The Award for Advanced Environmental Solutions recognizes a researcher or group of scientists that has achieved internationally significant R&D results in the field of environmental protection and recovery. The Eni Award is referred to as the Nobel Award in the fields of energy and environment.
Professor Lee, a pioneering leader in systems metabolic engineering was honored with the award for his developing engineered bacteria to produce chemical products, fuels, and non-food biomass materials sustainably and with a low environmental impact. He has leveraged the technology to develop microbial bioprocesses for the sustainable and environmentally friendly production of chemicals, fuels, and materials from non-food renewable biomass.
The award committee said that they considered the following elements in assessing Professor Lee’s achievement: the scientific relevance and the research innovation level; the impact on the energy system in terms of sustainability as well as fairer and broader access to energy; and the adequacy between technological and economic aspects.
Professor Lee, who already won two other distinguished prizes such as the George Washington Carver Award and the PV Danckwerts Memorial Lecture Award this year, said, “I am so glad that the international academic community as well as global industry leaders came to recognize our work that our students and research team has made for decades.”
Dr. Lee’s lab has been producing a lot of chemicals in environmentally friendly ways. Among them, many were biologically produced for the first time and some of these processes have been already commercialized. “We will continue to strive for research outcomes with two objectives: First, to develop bio-based processes suitable for sustainable chemical industry. The other is to contribute to the human healthcare system through development of platform technologies integrating medicine and nutrition,” he added.
2018.09.12 View 9597 -
Center for Industrial Future Strategy Takes Off at KAIST
(Professor Wonjoon Kim from the School of Business and Technology Management)
Professors from KAIST and major international universities launched a mega-scale research center focusing on the Fourth Industrial Revolution, named the Center for Industrial Future Strategy (CIFS).
This center is funded by the National Research Foundation Korea and will receive 2.25 billion KRW over four years.
Directed by Professor Wonjoon Kim from the School of Business and Technology Management, the center is comprised of ten top-tier researchers and four research associates, including Professor Hawoon Jeong (KAIST), Professor Scott Stern (MIT), Professor Aaron Chatterji (Duke University), Dr. Yong Suk Lee (Stanford University) and Professor Hyejin Youn (Northwestern University).
The center will conduct research on technical, social, and economic changes derived by a new paradigm of technological innovation.
Moreover, they will study policies and strategies in relation to innovation in the corporate and government sectors to achieve economic growth in a sustainable manner. The center will also propose policies and strategies in a variety of economic and industrial settings to establish a sustainable and global innovation ecosystem.
To carry out these studies successfully, CIFS will further expand the AIEA-NBER Conference with the Asia Innovation and Entrepreneurship Association (AIEA) and the National Bureau of Economic Research (NBER) in which numerous Nobel Laureates in Economics are affiliated. They will also comprise thematic research teams with co-founding universities to build stronger cooperation with one another.
Besides the academic cooperation, the center will also build partnerships with international organizations, including the Asian Development Bank and the Inter-American Development Bank to carry out their missions at multilateral levels.
Their research topics include changes to value chains in a new paradigm of technological innovation, labor market changes in the Fourth Industrial Revolution, sharing economies and social interests, big data, artificial intelligence & privacy policy, and innovation & ethical and institutional countermeasures to AI technology.
Professor Kim said, “The new paradigm of technological innovation is evolving social, economic, and industrial structures, such as R&D, industry, technology, labor, finance, and institutions. The Center will contribute to proposing policies and strategies so that Korea, as well as the international community, can take appropriate measures to these big changes.”
2018.09.11 View 12913 -
Electron Heating in Weakly Ionized Collisional Plasmas
(from left: Professor Wonho Choe and Research Professor Sanghoo Park)
A KAIST research team successfully identified the underlying principles behind electron heating, which is one of the most important phenomena in plasmas. As the electric heating determines wide range of physical and chemical properties of plasmas, this outcome will allow relevant industries to extend and effectively customize a range of plasma characteristics for their specific needs.
Plasma, frequently called the fourth state of matter, can be mostly formed by artificially energizing gases in standard temperature (25°C) and pressure (1 atm) range. Among the many types of plasma, atmospheric-pressure plasmas have been gaining a great deal of attention due to their unique features and applicability in various scientific and industrial fields.
Because plasma characteristics strongly depends on gas pressure in the sub-atmospheric to atmospheric pressure range, characterizing the plasma at different pressures is a prerequisite for understanding the fundamental principles of plasmas and for their industrial applications.
In that sense, information on the spatio-temporal evolution in the electron density and temperature is very important because various physical and chemical reactions within a plasma arise from electrons. Hence, electron heating has been an interesting topic in the field of plasma.
Because collisions between free electrons and neutral gases are frequent under atmospheric-pressure conditions, there are physical limits to measuring the electron density and temperature in plasmas using conventional diagnostic tools, thus the principles behind free electron heating could not be experimentally revealed.
Moreover, lacking information on a key parameter of electron heating and its controlling methods is troublesome and limit improving the reactivity and applicability of such plasmas.
To address these issues, Professor Wonho Choe and his team from the Department of Nuclear and Quantum Engineering employed neutral bremsstrahlung-based electron diagnostics in order to accurately examine the electron density and temperature in target plasmas. In addition, a novel imaging diagnostics for two dimensional distribution of electron information was developed.
Using the diagnostic technique they developed, the team measured the nanosecond-resolved electron temperature in weakly ionized collisional plasmas, and they succeeded in revealing the spatiotemporal distribution and the fundamental principle involved in the electron heating process.
The team successfully revealed the fundamental principle of the electron heating process under atmospheric to sub-atmospheric pressure (0.25-1atm) conditions through conducting the experiment on the spatiotemporal evolution of electron temperature.
Their findings of the underlying research data on free electrons in weakly ionized collisional plasmas will contribute to enhancing the field of plasma science and their commercial applications.
Professor Choe said, “The results of this study provide a clear picture of electron heating in weakly ionized plasmas under conditions where collisions between free electrons and neutral particles are frequent. We hope this study will be informative and helpful in utilizing and commercializing atmospheric-pressure plasma sources in the near future.”
Articles related to this research, led by Research Professor Sanghoo Park, were published in Scientific Reports on May 14 and July 5.
Figure 1. Nanosecond-resolved visualization of the electron heating structure. Spatiotemporal evolution of 514.5-nm continuum radiation,Te, Ar I emission
Figure 2. Nanosecond-resolved visualization of electron heating. Spatiotemporal evolution of neutral bremsstrahlung at 514.5 nm
2018.09.10 View 7888 -
There Won't Be a Singularity: Professor Jerry Kaplan
(Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST)
“People are so concerned about super intelligence, but the singularity will not happen,” said Professor Jerry Kaplan at Stanford University, an AI guru and Silicon Valley entrepreneur during a lecture at KAIST. He visited KAIST to give a lecture on Artificial Intelligence: Think Again on September 6.
Professor Kaplan said that some people argue that Korea’s AI research is behind the US and China but he doesn’t agree with that. “Korea is the most digitally connected one and has the world’s best engineers in the field. Korean companies are building products the consumers really like at reasonable prices. Those are attracting global consumers,” he added.
Instead of investing loads of money on AI research, he suggested three tasks for Korea taking a better position in the field of AI: Collecting and saving lots of data; training engineers, not the research talents in AI; and investing in AI infrastructure and relieving regulations by the government.
Referring to AI hype, Professor Kaplan argued that machines are intelligent, but they do not think in the way humans can, and assured the audience that the singularity some futurists predict will not be coming. He said, “Machine learning is a tool extracting useful information, but it does not mean they are so smart that they are taking over the world.”
(Professor Jerry Kaplan gave a lecture titled, Artificial Intelligence: Think Again at KAIST)
But what has made us believing AI myths? He first began pointing out how AI has been mythicized by three major drivers. Those are the entertainment industry, the popular media, and the AI community all wanting to attract more public attention and prestige. The abovementioned drivers are falsely making robots more human and are adding human characteristics.
Instead of being captivated by those AI myths and thinking about how to save the world from robots, he strongly argued, “We need to develop standards for the unintended side effects from AI.” To provide machines socially and ethically mingling with the human world, he believed principles should be set as follows: Define the Safe Operating Envelope (SOE), “safe modes” when out of bounds, study human behavior programmatically, certification and licensing standards, limitations on machine “agency,” and basic computational ethics such as when it is okay to break the law.
Professor Kaplan gave a positive view of AI for humans. “The future will be bright, thanks to AI. They do difficult work and help us and that will drive wealth and quality of life. The rich might get richer, but the benefits will spread throughout the people. It is time to think of innovative ways for using AI for building better world,” he concluded.
2018.09.10 View 6513 -
NEREC Summer Program Keeps Fellows Thinking, Engaged in Nuclear Nonproliferation
Nuclear technology is more than just technology. It is the fruit of the most advanced science and technology. It also requires high standards of policymaking and global cooperation for benefiting the technology.
As part of the fifth annual Nuclear Nonproliferation Education and Research Center (NEREC) Summer Fellows Program at KAIST, 24 students from 15 countries participated in six-week intensive education and training program. NEREC is the only university-based center dedicated to nuclear nonproliferation education and research established in 2014.
The program, which provides multidisciplinary lectures and seminars on nuclear technology and policy as well as international relations, was designed to nurture global nuclear technology experts well equipped in three areas: in-depth knowledge of technology, applicability gained from sound policy building, and negotiating for international cooperation. It now has grown into the most popular summer program at KAIST.
During the program from July 6 to August 18, participants were able to engage in enriching and stimulating learning experiences in tandem with policies and technology for the utilization and provision of peaceful and safe nuclear technology.
Participating fellows also had to conduct a group research project on a given topic. This year, they explored nuclear nonproliferation issues in relation to nuclear exports and brainstormed some recommendations for current policy. They presented their outcomes at the 2018 NEREC Conference on Nuclear Nonproliferation. After intensive lecture sessions and group research work, the fellows went off to key policy think-tanks, nuclear research institutes, and research power facilities in Korea, Japan, and China.
“NEREC emphasizes nuclear nonproliferation issues related to civilian nuclear power and the associated nuclear fuel cycle development from the point of technology users. I am very glad that the number of participants are increasing year by year,” said the Director of NEREC Man-Sung Yim, a professor in the Department of Nuclear and Quantum Engineering.
Participants’ majors vary from nuclear engineering to international relations to economics. The fellows divided into two groups of graduate and undergraduate courses. They expressed their deep satisfactory in the multidisciplinary lectures by scholars from KAIST, Seoul National University, and Korea National Defense University.
Many participants reported that they learned a lot, not only about policy and international relations but on the research they are conducting and what the key issues will be in dealing for producing meaningful research work.
Moad Aldbissi from the KTH Royal Institute of Technology is one of the students who shared the same view. He said, “Coming from a technical background in nuclear engineering, I managed to learn a lot about nuclear policy and international relations. The importance of integrating the technical and political fields became even clearer.”
Most students concurred that they recognized how important it was to make international collaboration in this powerful field for each country through this program.
“As an engineering student, I just approached this program like an empty glass in policy areas. While working with colleagues during the program, I came to understand how important it is to make cooperation in these fields for the better result of national development and international relations,” said Thanataon Pornphatdetaudom from the Tokyo Institute of Technology.
To Director Yim, this program is becoming well positioned to educate nuclear policy experts in a number of countries of strategic importance. He believes the continuous supply of these experts will contribute to promoting global nuclear nonproliferation and the peaceful use of nuclear energy while the use of nuclear technology continues.
2018.09.04 View 13232 -
Adding Smart to Science Museum
KAIST and the National Science Museum (NSM) created an Exhibition Research Center for Smart Science to launch exhibitions that integrate emerging technologies in the Fourth Industrial Revolution, including augmented reality (AR), virtual reality (VR), Internet of Things (IoTs), and artificial intelligence (AI).
There has been a great demand for a novel technology for better, user-oriented exhibition services. The NSM continuously faces the problem of not having enough professional guides. Additionally, there have been constant complaints about its current mobile application for exhibitions not being very effective.
To tackle these problems, the new center was founded, involving 11 institutes and universities. Sponsored by the National Research Foundation, it will oversee 15 projects in three areas: exhibition-based technology, exhibition operational technology, and exhibition content.
The group first aims to provide a location-based exhibition guide system service, which allows it to incorporate various technological services, such as AR/VR to visitors. An indoor locating system named KAILOS, which was developed by KAIST, will be applied to this service. They will also launch a mobile application service that provides audio-based exhibition guides.
To further cater to visitors’ needs, the group plans to apply a user-centered ecosystem, a living lab concept to create pleasant environment for visitors.
“Every year, hundred thousands of young people visit the National Science Museum. I believe that the exhibition guide system has to be innovative, using cutting-edge IT technology in order to help them cherish their dreams and inspirations through science,” Jeong Heoi Bae, President of Exhibition and Research Bureau of NSM, emphasized.
Professor Dong Soo Han from the School of Computing, who took the position of research head of the group, said, “We will systematically develop exhibition technology and contents for the science museum to create a platform for smart science museums. It will be the first time to provide an exhibition guide system that integrates AR/VR with an indoor location system.”
The center will first apply the new system to the NSM and then expand it to 167 science museums and other regional museums.
2018.09.04 View 11643 -
Potential Drug to Cure Ciliopathies
(from left: Professor Joon Kim and PhD candidate Yong Joon Kim)
Ciliopathies are rare disorders involving functional and structural abnormalities of cilia. Although they are rare, they may reach 1 in 1,000 births. Unfortunately, there are no small-molecule drugs for treating ciliary defects. A KAIST research team conducted successful research that introduces a potential treatment that will be a foundation for developing drugs to treat the disease as well as a platform for developing small-molecule drugs for similar genetic disorders.
It was found that mutations in genes required for the formation or function of primary cilia cause ciliopathies and they result in cerebellar disorders, kidney dysfunction, and retinal degeneration.
Primary cilia are cell organelles playing a crucial role in the human body. They participate in intercellular signal transduction during embryonic development and allow retinal photoreceptor cells to function.
Currently, there are no approved drugs available for treating most ciliopathies. In fact, this is the case for most of the rare genetic disorders involving functional abnormalities through genetic mutation, and gene therapy is usually the only treatment available.
To tackle this issue, a team led by Professor Joon Kim from the Graduate School of Medical Science and Engineering and Ho Jeong Kwon from Yonsei University constructed a cell that mimics a gene-mutated CEP290, one of the main causes of ciliopathies, through genome editing. They then used cell-based compound library screening to obtain a natural small-molecule compound capable of relieving defects in ciliogenesis, the production of cilia.
The CEP290 protein forms a complex with a ciliopathy protein called NPHP5 to support the function of the ciliary transition zone. In cases where the CEP290 protein is not formed due to a genetic mutation, NPHP5 will not function normally. Here, the compound was confirmed to partially restore the function of the complex by normalizing the function of NPHP5.
The team also identified that the compound is capable of retarding retinal degeneration by injecting the compound into animal models.
As a result, they discovered a lead compound for developing medication to treat ciliopathy patients involving retinal degeneration. Hence, the findings imply that chemical compounds that target other proteins interacting with the disease protein can mitigate shortages of a disease protein in recessive genetic disorders.
PhD candidate Yong Joon Kim stated, “This study shows how genetic disorders caused by genetic mutation can be treated with small-molecule drugs.”
Professor Kim said, “Since the efficacy of the candidate drug has been verified through animal testing, a follow-up study will also be conducted to demonstrate the effect on humans.”
This research was published in the Journal of Clinical Investigation on July 23.
Figure 1. Identification of compounds that rescue ciliogenesis defects caused by CEP290 knockout
Figure 2. Eupatilin injection ameliorates M-opsin trafficking and electrophysiological response of cone photoreceptors in rd16 mice
2018.08.30 View 9310 -
Metabolic Engineering of E. coli for the Secretory Production of Free Haem
Researchers of KAIST have defined a novel strategy for the secretory production of free haem using engineered Escherichia coli (E. coli) strains. They utilized the C5 pathway, the optimized downstream pathways, and the haem exporter to construct a recombinant micro-organism producing extracellular haem using fed-batch fermentation. This is the first report to extracellularly produce haem using engineered E. coli.
This strategy will expedite the efficient production of free haem to serve as a bioavailable iron-supplying agent and an important prosthetic group of multiple hemoproteins for medical uses. This study, led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering, was published in Nature Catalysis on Aug. 28.
Haem, an organometallic compound complexed with a ferrous ion, is an essential molecule delivering oxygen in the blood of many animals. It is also a key component of electron transport chains responsible for the respiration of aerobic organisms including diverse bacteria. It is now being widely applied as a bioavailable iron-supplying agent in the healthcare and dietary supplement industries. The demand for haem and the need for the efficient production of this compound continue to grow.
Many previous researchers have attempted to produce free haem using engineered E. coli. However, none of the studies was successful in producing free haem extracellularly, requiring an additional step to extract the accumulated haem from cells for subsequent uses. The secretion of haem in the form of haem peptides or proteins also requires an extraction step to isolate the free haem from the secreted products. Thus, the secretory production of free haem is an important task for the economical production of haem that is suitable for human consumption.
Although some researchers could produce intracellular haem using recombinant E. coli strains, its final titer was extremely low, resulting from the use of sub-optimal metabolic pathways. Furthermore, the addition of the precursors L-glycine and succinate was deemed undesirable for massive industrial production. Thus, it is necessary to construct an optimized haem biosynthetic pathway to enable the efficient production of haem and examine the consequent secretion of free haem.
To address this issue, the KAIST team used multiple strategies to produce extracellular free haem by enhancing its biosynthesis in E. coli. First, the capacities of the C4 and C5 pathways to produce aminolevulinate (ALA) without feeding precursors were examined. After confirming the superior performance of the C5 pathway over the C4 pathway, the metabolic genes of the C5 pathway and downstream pathways for haem biosynthesis were overexpressed. Then, the metabolic pathways were optimized by adjusting the expression levels of the relevant genes and disrupting the putative haem degradation enzyme encoded by the yfeX gene.
Consequently, the resulting engineered strain secreted a significant amount of haem to the medium. Subsequent optimization of the cultivation conditions and the supplementation of nitrogen sources further increased both the titer of the total free haem and the amount of free haem secreted to the medium. Finally, the overexpression of the ccmABC genes encoding the haem exporter further enhanced the production and secretion of haem, producing the highest titer of haem both intracellularly and extracellularly from glucose.
Professor Lee said, “The eco-friendly and sustainable chemical industry is a key global agenda every nation faces. We are conducting research to bio-synthesize high concentrations, high yields, and high productivity in natural products. This novel technology will serve as an opportunity to advance the biochemical industry moving forward.”
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. Further Contact: Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea ( leesy@kaist.ac.kr+82-42-350-3930).
2018.08.28 View 6552 -
'K-FLEX' Makes a Splash as a Flexible Endoscopic Surgical Robot
( Robot arms perform an incision during an ex-vivo test on a porcine gallbladder.)
K-FLEX, a flexible endoscopic surgical robot developed by the KAIST Future Medical Robotics Research Center, opens a new chapter for minimally invasive robot-assisted surgery with its precision control of 3.7 mm diameter robotic arms. The two arms, placing at the end of flexible endoscopes, highlight impeccable precision control and robust mini-joint design technologies. While cruising through the complicated inner body pliably, it carries out procedures on the spot with its robotic arms.
The research team under Professor Dong-Soo Kwon recently tested the device in-vivo, conducting a complicated endoscopic procedure dissecting a porcine gallbladder in collaboration with Professor Dae-Kyung Son of the National Cancer Center. The arms successfully manipulated the tissue safely.
During the test, K-FLEX, inserted through an incision in the navel, snaked through the narrow passages of the complicated inner organs. When reaching the desired spot, one of the robot arms pushed aside and held up the nearby tissue to secure proper vision and space for the procedure. Meanwhile, a cautery needle mounted at the tip of the other hand removed the lesion tissue on the gallbladder. The tiny camera installed at the front of the robot arms relayed the internal conditions. The full procedure was able to be monitored from the master console.
The two arms are placed onto 4.2 mm internal channels of an endoscope which is 17 mm in diameter. The arms can be deployable forward and backward and are extendable up to 7 cm for performing procedures.
K-FLEX is made of domestically produced components, except for the endoscopic module. It will expand new medical robotics research while offering novel therapeutic capabilities for endoscopes.
Flexible endoscopes are very promising for surgical applications because they can treat areas thought to be difficult to reach, such as the posterior side of an organ. Current rigid-type laparoscopic tools could not reach a lesion if it occurs in such serpentine and complicated areas. However, this flexible endoscopic surgery robot will bypass obstacles to reach the troubled area.
The ability to seamlessly integrate effective actuation into millimeter-scale deployable mechanisms fits well with minimally invasive surgical procedures. This flexible endoscopic surgery robot, only half the size of current laparoscopic surgical robots, is deployable into natural orifices such as the mouth, anus, and vagina without requiring external incisions. Laparoscopic devices and robots require at least three to four external incisions to insert the devices; however, the applicability of internal incisions reduces the possibility of complications arousing from excessive bleeding and bacterial infections.
Despite these advantages, it has remained challenging to manipulate the robotic arms of flexible endoscopes with integrated grabbing force, flexibility, and multiple degrees of freedom for clinical environments.
The team focused on smaller but smarter devices. Dr. Min-Ho Hwang, a principal researcher of K-FLEX, said that developing tiny robots that are able to generate the necessary forces without compromising safety was the challenge. They created a robust but smaller-joint technology that can exert a relatively greater force even into millimeter scale.
Professor Kwon said, “K-FLEX is the first flexible endoscopic surgery robot in Korea. We already confirmed the clinical adaptation through ex vivo tests and will see complete commercialization in two to three years.” The team believes K-FLEX will be very effective for surgery on incipient cancer cells in the stomach, colon, and thyroid.
Professor Kwon and his eight researchers recently established a tech start-up called EasyEndo Surgical Inc. with these core technologies. In June, K-FLEX won the ‘Best Application Award’ and the ‘Overall Winner’ at the Surgical Robot Challenge 2018 held at Imperial College London. The Korea Research Foundation funded the research on K-FLEX.
(The team conducts a procedure using K-FLEX, flexible endoscopic surgical robot.)
2018.08.17 View 10187