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Deep-Learning and 3D Holographic Microscopy Beats Scientists at Analyzing Cancer Immunotherapy
Live tracking and analyzing of the dynamics of chimeric antigen receptor (CAR) T-cells targeting cancer cells can open new avenues for the development of cancer immunotherapy. However, imaging via conventional microscopy approaches can result in cellular damage, and assessments of cell-to-cell interactions are extremely difficult and labor-intensive. When researchers applied deep learning and 3D holographic microscopy to the task, however, they not only avoided these difficultues but found that AI was better at it than humans were.
Artificial intelligence (AI) is helping researchers decipher images from a new holographic microscopy technique needed to investigate a key process in cancer immunotherapy “live” as it takes place. The AI transformed work that, if performed manually by scientists, would otherwise be incredibly labor-intensive and time-consuming into one that is not only effortless but done better than they could have done it themselves. The research, conducted by the team of Professor YongKeun Park from the Department of Physics, appeared in the journal eLife last December.
A critical stage in the development of the human immune system’s ability to respond not just generally to any invader (such as pathogens or cancer cells) but specifically to that particular type of invader and remember it should it attempt to invade again is the formation of a junction between an immune cell called a T-cell and a cell that presents the antigen, or part of the invader that is causing the problem, to it. This process is like when a picture of a suspect is sent to a police car so that the officers can recognize the criminal they are trying to track down. The junction between the two cells, called the immunological synapse, or IS, is the key process in teaching the immune system how to recognize a specific type of invader.
Since the formation of the IS junction is such a critical step for the initiation of an antigen-specific immune response, various techniques allowing researchers to observe the process as it happens have been used to study its dynamics. Most of these live imaging techniques rely on fluorescence microscopy, where genetic tweaking causes part of a protein from a cell to fluoresce, in turn allowing the subject to be tracked via fluorescence rather than via the reflected light used in many conventional microscopy techniques.
However, fluorescence-based imaging can suffer from effects such as photo-bleaching and photo-toxicity, preventing the assessment of dynamic changes in the IS junction process over the long term. Fluorescence-based imaging still involves illumination, whereupon the fluorophores (chemical compounds that cause the fluorescence) emit light of a different color. Photo-bleaching or photo-toxicity occur when the subject is exposed to too much illumination, resulting in chemical alteration or cellular damage.
One recent option that does away with fluorescent labelling and thereby avoids such problems is 3D holographic microscopy or holotomography (HT). In this technique, the refractive index (the way that light changes direction when encountering a substance with a different density—why a straw looks like it bends in a glass of water) is recorded in 3D as a hologram.
Until now, HT has been used to study single cells, but never cell-cell interactions involved in immune responses. One of the main reasons is the difficulty of “segmentation,” or distinguishing the different parts of a cell and thus distinguishing between the interacting cells; in other words, deciphering which part belongs to which cell.
Manual segmentation, or marking out the different parts manually, is one option, but it is difficult and time-consuming, especially in three dimensions. To overcome this problem, automatic segmentation has been developed in which simple computer algorithms perform the identification.
“But these basic algorithms often make mistakes,” explained Professor YongKeun Park, “particularly with respect to adjoining segmentation, which of course is exactly what is occurring here in the immune response we’re most interested in.”
So, the researchers applied a deep learning framework to the HT segmentation problem. Deep learning is a type of machine learning in which artificial neural networks based on the human brain recognize patterns in a way that is similar to how humans do this. Regular machine learning requires data as an input that has already been labelled. The AI “learns” by understanding the labeled data and then recognizes the concept that has been labelled when it is fed novel data. For example, AI trained on a thousand images of cats labelled “cat” should be able to recognize a cat the next time it encounters an image with a cat in it. Deep learning involves multiple layers of artificial neural networks attacking much larger, but unlabeled datasets, in which the AI develops its own ‘labels’ for concepts it encounters.
In essence, the deep learning framework that KAIST researchers developed, called DeepIS, came up with its own concepts by which it distinguishes the different parts of the IS junction process. To validate this method, the research team applied it to the dynamics of a particular IS junction formed between chimeric antigen receptor (CAR) T-cells and target cancer cells. They then compared the results to what they would normally have done: the laborious process of performing the segmentation manually. They found not only that DeepIS was able to define areas within the IS with high accuracy, but that the technique was even able to capture information about the total distribution of proteins within the IS that may not have been easily measured using conventional techniques.
“In addition to allowing us to avoid the drudgery of manual segmentation and the problems of photo-bleaching and photo-toxicity, we found that the AI actually did a better job,” Professor Park added.
The next step will be to combine the technique with methods of measuring how much physical force is applied by different parts of the IS junction, such as holographic optical tweezers or traction force microscopy.
-Profile
Professor YongKeun Park
Department of Physics
Biomedical Optics Laboratory
http://bmol.kaist.ac.kr
KAIST
2021.02.24 View 13467 -
KAIST Celebrates 50-Year Anniversary with 2,712 New Graduates via 2021 Commencement Ceremony
KAIST is proud to announce the graduation of 2,712 students, including 668 PhDs and 1,331 master’s degree recipients. The pandemic could not stop the university from recognizing each graduate's remarkable and original achievements. A pandemic-proof blended commencement ceremony was held on Friday, February 19, and livestreamed to the graduates and their loved ones.
KAIST decided to take extra precautions to protect graduates and other attendees’ health and well-being.
For the virtual ceremony, only 83 out of the 2,712 graduates were invited to attend the ceremony in person. Graduates were divided into four groups to attend at four different places in Daejeon and Seoul campuses and watch the ceremony via Zoom. No family members or friends of the graduates were allowed to participate at the campus, but happily cheered the graduates via YouTube.
This year’s valedictorian, Hyun-Young Park from the School of Electrical Engineering, received the Award of the Minister of Science and ICT. Salutorian Yeh-Lin Cho from the Department of Materials Science and Engineering received the Award of the KAIST Board of Trustees, while the recipient of the KAIST Presidential Award was Min-Jae Kim from the Department of Bio and Brain Engineering. The Award of the KAIST Development Foundation Chairman and the KAIST Alumni Association Presidential Award were conferred to Kyung-Tae Kim from the Department of Physics and Min-Woo Jung from the Department of Civil and Environmental Engineering, respectively.
President Sung-Chul Shin, Chairman of the Board of Trustees Woo Sik Kim, and a very limited number of faculty members and administrative staff officiated the commencement ceremony from the KAIST Auditorium.
President Shin applauded the graduates’ hard work and dedication in his commencement speech. He also delivered a very special congratulatory message to the bachelor’s degree awardees.
“This year’s commencement is especially meaningful for me. I was appointed as the 16th president of KAIST on February 23, 2017, and met you for the first time on February 28 at the matriculation ceremony. We promised each other—as freshmen and as the first alumnus president—to do our best for the next four years,” President Shin recalled.
He added, “I have done my best to keep my promise, and now my term will end on February 22. Of course, the past four years were even more precious because you were all a part of it.”
In conclusion, President Shin said, “I am proud of you for keeping your end of the promise. Thank you for becoming who you are today. I have high hopes for the bright future that you will be shaping for KAIST and our society.”
The livestream ceremony is archived for viewing on KAIST's Official YouTube Channel.
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2021.02.19 View 9781 -
Provost Kwang Hyung Lee Elected as the 17th President of KAIST
Provost and Executive Vice President Kwang Hyung Lee was selected as the 17th president of KAIST during a vote of the KAIST Board of Trustees on February 18. He will succeed President Sung-Chul Shin, whose four-year term concludes on February 22.
President-elect Lee, 67, was among the three final candidates who were nominated by the Presidential Search Committee. Upon the selection, President-elect Lee said he will take up new challenges to transform KAIST into the most relevant research university in the world, fostering talents who can work with emerging technologies while pushing for innovative R&D initiatives that will benefit all of humanity.
President-elect Lee is a futurologist who pioneered multidisciplinary studies and research at KAIST. He advocated that the convergence of information, biology, and nano-technologies would be critical for future industries, playing a crucial role in establishing the Department of Bio and Brain Engineering in 2001 and the Moon Soul Graduate School of Future Strategy in 2013. He then served as the inaugural head of both faculties.
President-elect Lee has extensive administrative experience at KAIST, serving as Associate Vice President of the International Office, and Associate Vice President of Academic Affairs since early 2001. He is also serving as a member of the Korea Presidential Education Committee.
An ardent champion of entrepreneurship and startups, he has advised the first generations of KAIST startup entrepreneurs such as Nexon, Idis, Neowiz, and Olaworks. President-elect Lee, drawn to creative thinking and flipped learning, is famous for watching TV upside down. Such pioneering ideas and his unusual thinking style were modeled in the ‘eccentric professor’ role featured on the TV hit drama of ‘KAIST’ from 1999 to 2000.
An alumnus who earned his MS in industrial engineering at KAIST in 1980 after completing his undergraduate studies at Seoul National University, President-elect Lee joined the KAIST faculty in 1985 upon receiving his PhD in computer science from INSA de Lyon in France.
A computer scientist as well as fuzzy theorist whose research area extends to AI, bioinformatics, fuzzy intelligent systems, and foresight methods, Professor Lee has published more than 70 papers in international journals and textbooks on system programming, fuzzy set theory and its applications, and three-dimensional creativity. He also invented a fuzzy elevator, subway operation controller, and AI transportation controller.
A fellow at the Korea Academy of Science and Technology and the National Academy of Engineering of Korea, he was decorated by the Korean government and the French government in recognition of the innovative education and research initiatives he has pursued.
2021.02.18 View 10274 -
Distinguished Alumni Awardees 2020
The KAIST Alumni Association (KAA) announced the four recipients of the Distinguished Alumni Awards for the year 2020.
The Distinguished Alumni Awards recognize graduates who have achieved outstanding accomplishments in their professional and personal lives, and who have been an inspiration to fellow alumni and students in Korea and around the globe. The four distinguished alumni of the year 2020 are listed below.
President Dong-Won Kim (Department of Industrial and Systems Engineering, M.S., Class of ’82) of Jeonbuk National University is making significant contributions to the advancement of local industrial technology and the cultivation of professional personnel through outstanding research outcomes. As an educational administrator, his leadership is helping to realize long-desired projects at the university, through which he is strengthening the competitiveness of the university and the local community.
Tae-Kyung Yoo (School of Electrical Engineering, M.S. and Ph.D., Class of ’83 and ’85 respectively), CEO and Chairman of Lumens, is a first-generation entrepreneur in the light emitting diode (LED) industry in Korea. He runs Lumens, a globally renowned company specializing in and leading the technological innovation of LEDs. He thereby contributes to strengthening national competitiveness and the advancement of science and technology.
President Nak Kyu Lee (Department of Mechanical Engineering, M.S. and Ph.D., Class of ’85 and ’87 respectively) of the Korea Institute of Industrial Technology (KITECH) has shown excellent results in his research in which he developed core production technologies to lead the nation’s industries. He also focused on supporting on-site technologies involved in field work to apply what he developed into real production processes, and contributed greatly to improving the competitiveness of nationwide manufacturing.
Hyeon-Mo Ku (School of Business and Technology Management, M.S. and Ph.D., Class of ’85 and ’93 respectively), CEO of KT Corporation, helped the nation’s leading communications company roll out the first 5G network in the world. He also strengthened national competitiveness in AI technology through ‘AI One Team,’ an industry-academic corporation project, and took the lead in developing the home-grown cloud industry. His involvement in the innovation of Korea’s ICT technology was highly recognized.
Since the establishment of the award in 1992, a total of 107 alumni at home and abroad have brought distinction to the university and been honored as recipients.
These recipients are playing major roles in society, and some of the notable former awardees include: KAIST President Sung-Chul Shin (2010), Samsung Electronics Vice Chairman Ki-Nam Kim (2012), Nexon Chairman Jung-Ju Kim (2007), and Krafton Chairman Byeong-Gyu Chang (2006).
The President of the KAA and Advisor of Samsung Electronics, Chilhee Chung, said, “The Distinguished Alumni Awards are an honor given to alumni who have contributed to the development of the nation and society, and raised the name of their alma mater.” He added, “We can see the proud position of KAIST in the global arena just by looking at the accomplishments of our awardees.”
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2021.02.04 View 9545 -
COVID-Update: Spring 2021 Classes Continue Online
KAIST announced that its spring 2021 classes will also be online as the pandemic continues into the new year. The spring semester will begin on March 1.
Executive Vice President and Provost Kwang Hyung Lee said in a letter to the KAIST community on January 15 that nearly all classes in the 2021 spring semester will be held online. However, a very limited number of lab classes and other classes that require on-site practice and demonstrations will be offered either in-person or in a blended format. In addition, graduate courses above the 600 level and graduate courses in the College of Business at the Seoul campus will be allowed to conduct in-person or blended classes under very strict social distancing guidelines.
Provost Lee said that the university will be revert back to in-person classes as soon as the government eases the social distancing guidelines. As of February 4, the nation is under Level 2.5 in Seoul and its metropolitan areas, while other regions are at Level 2. Level 2.5 prohibits the gathering of 10 or more people, and Levels 1 and 2 require gatherings to be fewer than 50 people. At Level 3, all classes will be held online.
Test management is another challenge. Regarding mid-term and final exams, the university plans to give more flexibility to professors. Professors may give additional assignments instead of a mid-term exam. Open-book exams and real-time exams through Zoom will be another option. However, some classes that require in-person tests in some graduate courses will be allowed as long as they follow very strict social distancing guidelines.
2021.02.04 View 6023 -
Highly Deformable Piezoelectric Nanotruss for Tactile Electronics
With the importance of non-contact environments growing due to COVID-19, tactile electronic devices using haptic technology are gaining traction as new mediums of communication.
Haptic technology is being applied in a wide array of fields such as robotics or interactive displays. haptic gloves are being used for augmented information communication technology. Efficient piezoelectric materials that can convert various mechanical stimuli into electrical signals and vice versa are a prerequisite for advancing high-performing haptic technology.
A research team led by Professor Seungbum Hong confirmed the potential of tactile devices by developing ceramic piezoelectric materials that are three times more deformable. For the fabrication of highly deformable nanomaterials, the research team built a zinc oxide hollow nanostructure using proximity field nanopatterning and atomic layered deposition. The piezoelectric coefficient was measured to be approximately 9.2 pm/V and the nanopillar compression test showed an elastic strain limit of approximately 10%, which is more than three times greater than that of the bulk zinc oxide one.
Piezoelectric ceramics have a high piezoelectric coefficient with a low elastic strain limit, whereas the opposite is true for piezoelectric polymers. Therefore, it has been very challenging to obtain good performance in both high piezoelectric coefficients as well as high elastic strain limits. To break the elastic limit of piezoelectric ceramics, the research team introduced a 3D truss-like hollow nanostructure with nanometer-scale thin walls.
According to the Griffith criterion, the fracture strength of a material is inversely proportional to the square root of the preexisting flaw size. However, a large flaw is less likely to occur in a small structure, which, in turn, enhances the strength of the material. Therefore, implementing the form of a 3D truss-like hollow nanostructure with nanometer-scale thin walls can extend the elastic limit of the material. Furthermore, a monolithic 3D structure can withstand large strains in all directions while simultaneously preventing the loss from the bottleneck. Previously, the fracture property of piezoelectric ceramic materials was difficult to control, owing to the large variance in crack sizes. However, the research team structurally limited the crack sizes to manage the fracture properties.
Professor Hong’s results demonstrate the potential for the development of highly deformable ceramic piezoelectric materials by improving the elastic limit using a 3D hollow nanostructure. Since zinc oxide has a relatively low piezoelectric coefficient compared to other piezoelectric ceramic materials, applying the proposed structure to such components promised better results in terms of the piezoelectric activity.
“With the advent of the non-contact era, the importance of emotional communication is increasing. Through the development of novel tactile interaction technologies, in addition to the current visual and auditory communication, mankind will enter a new era where they can communicate with anyone using all five senses regardless of location as if they are with them in person,” Professor Hong said.
“While additional research must be conducted to realize the application of the proposed designs for haptic enhancement devices, this study holds high value in that it resolves one of the most challenging issues in the use of piezoelectric ceramics, specifically opening new possibilities for their application by overcoming their mechanical constraints.
The research was reported in Nano Energy and supported by the Ministry of Science and ICT, the Korea Research Foundation, and the KAIST Global Singularity Research Project.
-Profile: Professor Seungbum Hong
seungbum@kaist.ac.kr
http://mii.kaist.ac.kr/
Department of Materials Science and Engineering
KAIST
2021.02.02 View 11782 -
Top University Leaders Urge Innovation for the Post-COVID Era at the KAIST Summit
- Presidents of KAIST, MIT, Tokyo Tech, and Northwestern to define new roles and responsibilities of universities for the post-COVID and 4IR eras during an online summit in celebration of KAIST’s 50th anniversary. -
Universities are facing ever-mounting pressure to address impacts brought on by COVID-19 and the emerging technologies of the Fourth Industrial Revolution (4IR).
Presidents from MIT, Tokyo Tech, and Northwestern University will join the KAIST Summit to explore new directions for higher education during the post-COVID era intertwined with the 4IR. They agree that addressing these dual challenges requires pushing for innovations to rebuild the competitive edges of universities.
This summit is one of KAIST’s series of events to envision the future of KAIST and higher education in celebration of its 50th anniversary. The online summit will be live streamed on KAIST’s official YouTube channel (https://www.youtube.com/c/KAISTofficial) on February 3, 2021, from 10 a.m. to 12:00 p.m. Korean time (February 2, 7:00-9:00 p.m. CST and 8:00-10:00 p.m. EST, respectively).
The KAIST Summit titled “The Roles and Responsibilities of Universities in a Global Crisis” will discuss a range of issues affecting many aspects of universities in the coming decades.
“This summit will allow us to measure the level of risk that universities face today and will face in the future. Although there will be varying views on what a post-COVID world might look like, one thing for sure is that universities cannot go back to the way they used to exist and operate. Moreover, the 4IR continues to infiltrate and shake up our daily lives. Changes are inevitable, and universities must pursue bold and innovative responses to remain sustainable and relevant to society,” said KAIST President Sung-Chul Shin on the background of hosting the event.
The keynote speakers include KAIST President Shin, MIT President L. Rafael Reif, Tokyo Tech President Kazuya Masu, and Northwestern University President Morton Schapiro. After the keynote speech session, the speakers will take part in a panel discussion on three topics: “The Digital Divide,” “Emerging Challenges in AI,” and “Social Entrepreneurship and University-Industry Collaboration.” A Q&A session with an online audience consisting of KAIST faculty, staff, and students as well as high school students across the nation will follow shortly afterwards.
President Reif of MIT will congratulate KAIST on its successful 50-year journey from meager beginnings to achieving its current status as one of the finest global universities in science and technology. Then he will give a talk titled “Universities as Engines of Change” to present how universities have played a critical role in advancing solutions to humanity’s most urgent problems.
President Masu of Tokyo Tech will stress the importance of universities’ continuous dialogue with society as drivers of innovation. In his speech titled “Designing Our Future—Tokyo Tech DLab’s Approach,” he will introduce the activities of Tokyo Tech’s Laboratory for Design of Social Innovation in Global Networks (DLab) and explain how DLab collaborates for the future with members of society.
President Schapiro of Northwestern University will speak about how universities might incorporate the lessons they learned in dealing with COVID-19 to improve their research, teaching, and public service in the post-pandemic era. He will also look into issues arising from changing labor market needs associated with the 4IR and the aftermath of COVID-19 in his talk titled “The University in the ‘New Normal.’”
Finally, President Shin of KAIST will deliver a presentation on the “Visions & Innovations for the Next Dream of KAIST.” He will reflect on the remarkable track record from KAIST’s first 50 years and how it has contributed significantly to the rapid growth of Korea as a hi-tech powerhouse. Furthermore, he will elaborate on a new vision for the development of KAIST over the next 50 years and roll out a set of strategic innovation plans in the five areas of education, research, technology commercialization, globalization, and future strategy.
In the panel discussion, the four presidents will dive into a more intense conversation on such topics as universities’ role in bridging the increasing digital divide through their research, education, and international cooperation; the socioeconomic implications and ethical challenges of the fast deployment of AI and robotics; 4IR disruptions that will transform higher education; ways to foster social innovation and youth entrepreneurship; and how to build university-industry cooperation.
More information on KAIST’s 50th anniversary celebrations can be found on its special celebratory website at https://50.kaist.ac.kr/eng/. The official anniversary ceremony is scheduled for February 16, 2021, from 10 a.m. Korean time, and live-streaming will also be made available on KAIST’s official YouTube channel at https://www.youtube.com/c/KAISTofficial.
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2021.02.01 View 16470 -
Wirelessly Rechargeable Soft Brain Implant Controls Brain Cells
Researchers have invented a smartphone-controlled soft brain implant that can be recharged wirelessly from outside the body. It enables long-term neural circuit manipulation without the need for periodic disruptive surgeries to replace the battery of the implant. Scientists believe this technology can help uncover and treat psychiatric disorders and neurodegenerative diseases such as addiction, depression, and Parkinson’s.
A group of KAIST researchers and collaborators have engineered a tiny brain implant that can be wirelessly recharged from outside the body to control brain circuits for long periods of time without battery replacement. The device is constructed of ultra-soft and bio-compliant polymers to help provide long-term compatibility with tissue. Geared with micrometer-sized LEDs (equivalent to the size of a grain of salt) mounted on ultrathin probes (the thickness of a human hair), it can wirelessly manipulate target neurons in the deep brain using light.
This study, led by Professor Jae-Woong Jeong, is a step forward from the wireless head-mounted implant neural device he developed in 2019. That previous version could indefinitely deliver multiple drugs and light stimulation treatment wirelessly by using a smartphone. For more, Manipulating Brain Cells by Smartphone.
For the new upgraded version, the research team came up with a fully implantable, soft optoelectronic system that can be remotely and selectively controlled by a smartphone. This research was published on January 22, 2021 in Nature Communications.
The new wireless charging technology addresses the limitations of current brain implants. Wireless implantable device technologies have recently become popular as alternatives to conventional tethered implants, because they help minimize stress and inflammation in freely-moving animals during brain studies, which in turn enhance the lifetime of the devices. However, such devices require either intermittent surgeries to replace discharged batteries, or special and bulky wireless power setups, which limit experimental options as well as the scalability of animal experiments.
“This powerful device eliminates the need for additional painful surgeries to replace an exhausted battery in the implant, allowing seamless chronic neuromodulation,” said Professor Jeong. “We believe that the same basic technology can be applied to various types of implants, including deep brain stimulators, and cardiac and gastric pacemakers, to reduce the burden on patients for long-term use within the body.”
To enable wireless battery charging and controls, researchers developed a tiny circuit that integrates a wireless energy harvester with a coil antenna and a Bluetooth low-energy chip. An alternating magnetic field can harmlessly penetrate through tissue, and generate electricity inside the device to charge the battery. Then the battery-powered Bluetooth implant delivers programmable patterns of light to brain cells using an “easy-to-use” smartphone app for real-time brain control.
“This device can be operated anywhere and anytime to manipulate neural circuits, which makes it a highly versatile tool for investigating brain functions,” said lead author Choong Yeon Kim, a researcher at KAIST.
Neuroscientists successfully tested these implants in rats and demonstrated their ability to suppress cocaine-induced behaviour after the rats were injected with cocaine. This was achieved by precise light stimulation of relevant target neurons in their brains using the smartphone-controlled LEDs. Furthermore, the battery in the implants could be repeatedly recharged while the rats were behaving freely, thus minimizing any physical interruption to the experiments.
“Wireless battery re-charging makes experimental procedures much less complicated,” said the co-lead author Min Jeong Ku, a researcher at Yonsei University’s College of Medicine.
“The fact that we can control a specific behaviour of animals, by delivering light stimulation into the brain just with a simple manipulation of smartphone app, watching freely moving animals nearby, is very interesting and stimulates a lot of imagination,” said Jeong-Hoon Kim, a professor of physiology at Yonsei University’s College of Medicine. “This technology will facilitate various avenues of brain research.”
The researchers believe this brain implant technology may lead to new opportunities for brain research and therapeutic intervention to treat diseases in the brain and other organs.
This work was supported by grants from the National Research Foundation of Korea and the KAIST Global Singularity Research Program.
-Profile
Professor Jae-Woong Jeong
https://www.jeongresearch.org/
School of Electrical Engineering
KAIST
2021.01.26 View 26981 -
Expanding the Biosynthetic Pathway via Retrobiosynthesis
- Researchers reports a new strategy for the microbial production of multiple short-chain primary amines via retrobiosynthesis. -
KAIST metabolic engineers presented the bio-based production of multiple short-chain primary amines that have a wide range of applications in chemical industries for the first time. The research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering designed the novel biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step.
The research team verified the newly designed pathways by confirming the in vivo production of 10 short-chain primary amines by supplying the precursors. Furthermore, the platform Escherichia coli strains were metabolically engineered to produce three proof-of-concept short-chain primary amines from glucose, demonstrating the possibility of the bio-based production of diverse short-chain primary amines from renewable resources. The research team said this study expands the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple short-chain primary amines as examples.
Currently, most of the industrial chemicals used in our daily lives are produced with petroleum-based products. However, there are several serious issues with the petroleum industry such as the depletion of fossil fuel reserves and environmental problems including global warming. To solve these problems, the sustainable production of industrial chemicals and materials is being explored with microorganisms as cell factories and renewable non-food biomass as raw materials for alternative to petroleum-based products. The engineering of these microorganisms has increasingly become more efficient and effective with the help of systems metabolic engineering – a practice of engineering the metabolism of a living organism toward the production of a desired metabolite. In this regard, the number of chemicals produced using biomass as a raw material has substantially increased.
Although the scope of chemicals that are producible using microorganisms continues to expand through advances in systems metabolic engineering, the biological production of short-chain primary amines has not yet been reported despite their industrial importance. Short-chain primary amines are the chemicals that have an alkyl or aryl group in the place of a hydrogen atom in ammonia with carbon chain lengths ranging from C1 to C7. Short-chain primary amines have a wide range of applications in chemical industries, for example, as a precursor for pharmaceuticals (e.g., antidiabetic and antihypertensive drugs), agrochemicals (e.g., herbicides, fungicides and insecticides), solvents, and vulcanization accelerators for rubber and plasticizers. The market size of short-chain primary amines was estimated to be more than 4 billion US dollars in 2014.
The main reason why the bio-based production of short-chain primary amines was not yet possible was due to their unknown biosynthetic pathways. Therefore, the team designed synthetic biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step. The retrobiosynthesis allowed the systematic design of a biosynthetic pathway for short-chain primary amines by using a set of biochemical reaction rules that describe chemical transformation patterns between a substrate and product molecules at an atomic level.
These multiple precursors predicted for the possible biosynthesis of each short-chain primary amine were sequentially narrowed down by using the precursor selection step for efficient metabolic engineering experiments.
“Our research demonstrates the possibility of the renewable production of short-chain primary amines for the first time. We are planning to increase production efficiencies of short-chain primary amines. We believe that our study will play an important role in the development of sustainable and eco-friendly bio-based industries and the reorganization of the chemical industry, which is mandatory for solving the environmental problems threating the survival of mankind,” said Professor Lee.
This paper titled “Microbial production of multiple short-chain primary amines via retrobiosynthesis” was published in Nature Communications. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.
-Publication
Dong In Kim, Tong Un Chae, Hyun Uk Kim, Woo Dae Jang, and Sang Yup Lee. Microbial production of multiple short-chain primary amines via retrobiosynthesis. Nature Communications ( https://www.nature.com/articles/s41467-020-20423-6)
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
Metabolic &Biomolecular Engineering National Research Laboratory
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
2021.01.14 View 13064 -
Professor Poong Hyun Seong Elected INSC Chair
Professor Emeritus Poong Hyun Seong from the Department of Nuclear and Quantum Engineering was elected as the Chairman of the International Nuclear Societies Council (INSC). His two-year term began on January 1.
The INSC is an organization made up of nuclear societies all over the world, representing more than 80,000 nuclear professionals. The INSC founded in 1990 acts as a global forum to establish common goals of nuclear power usage, delivering the views and ideas of professionals throughout their regional societies.
The INSC has advocated for nuclear power to be deemed an indispensable clean energy resources that can mitigate the climate change. The council has engaged in public awareness and publicity activities promoting the advantages of nuclear energy for developing next-generation power plants such as small nuclear reactors, local heating system, seawater desalination, and fair production of energy.
Professor Seong is a globally renowned scholar in the fields of nuclear instrumentation control and human factor engineering. He retired last year after 30-year career at KAIST. He took on leadership roles in the Korea Nuclear Society and served as a member of the Korea Nuclear Safety and Security Commission as well as Atomic Energy Commission. A fellow at the America Nuclear Society, Professor Seong served as the first vice chair of the INSC and he received the Don Miller Award in 2019. The award established in 2009 by the American Nuclear Society in honor of former ANS President Don Miller is given to an individual who has made a significant contribution to the advancement of nuclear instrumentation and control of human-machine interfaces.
He led the leadership role to help the Korean government steered into efficient and reasonable energy policymaking. More recently, as the Korean government decided to abandon nuclear energy, he actively opposed the government’s pivot. Professor Seong said, “Advanced countries like the US, UK, France, and Japan push forward the production of renewable energy by driving nuclear power plant under their pledges toward carbon neutrality by 2050. However, we are very concerned about the government’s policy shift to decrease the number of nuclear power plants while increasing the fossil fuel usage. I don’t think we can realize carbon neutrality by 2050 with the current policy.”
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2021.01.13 View 7489 -
KAIST Mobile Clinic Module to Fill Negative Pressure Ward Shortage
Efficient versatile ready-for-rapid building system of MCM will serve as both a triage unit and bridge center in emergency medical situations
A team from KAIST has developed a low-cost and ready-for-rapid-production negative pressure room called a Mobile Clinic Module (MCM). The MCM is expandable, moveable, and easy to store through a combination of negative pressure frames, air tents, and multi-function panels.
The MCM expects to quickly meet the high demand for negative pressure beds in the nation and eventually many other countries where the third wave of COVID-19 is raging. The module is now ready to be rolled out after a three-week test period at the Korea Cancer Center Hospital.
Professor Tek-Jin Nam’s team swung into action, rapidly working together with researchers, engineers with expertise in mechanical design, and a team of clinical doctors to complete the MCM as one of KAIST’s New Deal R&D initiatives launched last July.
Professor Nam cites ‘expandability’ as the key feature of the MCM. Eventually, it will serve as both a triage unit and bridge center in emergency medical situations.
“The module is a very efficient and versatile unit building system. It takes approximately two hours to build the basic MCM unit, which comprises four negative pressure bed rooms, nurse’s station, locker room, and treatment room. We believe this will significantly contribute to relieving the drastic need for negative pressure beds and provide a place for monitoring patients with moderate symptoms,” said Professor Nam.
“It will also be helpful for managing less-severe patients who need to be monitored daily in quarantined rooms or as bridge stations where on-site medical staff can provide treatment and daily monitoring before hospitalization. These wards can be efficiently deployed either inside or outside existing hospitals.”
The research team specially designed the negative pressure frame to ensure safety level A for the negative pressure room, which is made of a multi-function panel wall and roofed with an air tent. The multi-function panels can hold medical appliances such as ventilators, oxygen and bio-signal monitors.
Positive air pressure devices supply fresh air from outside the tent. An air pump and controller maintain air beam pressure, while filtering exhausted air. An internal air information monitoring system efficiently controls room air pressure and purifies the air.
While a conventional negative pressure bed is reported to cost approximately 3.5 billion KRW (50 billion won for a ward), this module is estimated to cost 0.75 billion won each (10 billion won for a ward), cutting the costs by approximately 80%.
The MCM is designed to be easily transported and relocated due to its volume, weight, and maintainability. This module requires only one-fourth of the volume of existing wards and takes up approximately 40% of their weight. The unit can be transported in a 40-foot container truck.
“We believe this will significantly contribute to relieving the drastic need for negative pressure beds and provide a place for monitoring patients with moderate symptoms. We look forward to the MCM upgrading epidemic management resources around the world.”
Professor Nam’s team is also developing antiviral solutions and devices such as protective gear, sterilizers, and test kits under the KAIST New Deal R&D Initiative that was launched to promptly and proactively respond to the epidemic. More than 45 faculty members and researchers at KAIST are collaborating with industry and clinical hospitals to develop the antiviral technology that will improve preventive measures, diagnoses, and treatment.
2021.01.07 View 12782 -
Astrocytes Eat Connections to Maintain Plasticity in Adult Brains
Developing brains constantly sprout new neuronal connections called synapses as they learn and remember. Important connections — the ones that are repeatedly introduced, such as how to avoid danger — are nurtured and reinforced, while connections deemed unnecessary are pruned away. Adult brains undergo similar pruning, but it was unclear how or why synapses in the adult brain get eliminated.
Now, a team of KAIST researchers has found the mechanism underlying plasticity and, potentially, neurological disorders in adult brains. They published their findings on December 23 in Nature.
“Our findings have profound implications for our understanding of how neural circuits change during learning and memory, as well as in diseases,” said paper author Won-Suk Chung, an assistant professor in the Department of Biological Sciences at KAIST. “Changes in synapse number have strong association with the prevalence of various neurological disorders, such as autism spectrum disorder, schizophrenia, frontotemporal dementia, and several forms of seizures.”
Gray matter in the brain contains microglia and astrocytes, two complementary cells that, among other things, support neurons and synapses. Microglial are a frontline immunity defense, responsible for eating pathogens and dead cells, and astrocytes are star-shaped cells that help structure the brain and maintain homeostasis by helping to control signaling between neurons. According to Professor Chung, it is generally thought that microglial eat synapses as part of its clean-up effort in a process known as phagocytosis.
“Using novel tools, we show that, for the first time, it is astrocytes and not microglia that constantly eliminate excessive and unnecessary adult excitatory synaptic connections in response to neuronal activity,” Professor Chung said. “Our paper challenges the general consensus in this field that microglia are the primary synapse phagocytes that control synapse numbers in the brain.”
Professor Chung and his team developed a molecular sensor to detect synapse elimination by glial cells and quantified how often and by which type of cell synapses were eliminated. They also deployed it in a mouse model without MEGF10, the gene that allows astrocytes to eliminate synapses. Adult animals with this defective astrocytic phagocytosis had unusually increased excitatory synapse numbers in the hippocampus. Through a collaboration with Dr. Hyungju Park at KBRI, they showed that these increased excitatory synapses are functionally impaired, which cause defective learning and memory formation in MEGF10 deleted animals.
“Through this process, we show that, at least in the adult hippocampal CA1 region, astrocytes are the major player in eliminating synapses, and this astrocytic function is essential for controlling synapse number and plasticity,” Chung said.
Professor Chung noted that researchers are only beginning to understand how synapse elimination affects maturation and homeostasis in the brain. In his group’s preliminary data in other brain regions, it appears that each region has different rates of synaptic elimination by astrocytes. They suspect a variety of internal and external factors are influencing how astrocytes modulate each regional circuit, and plan to elucidate these variables.
“Our long-term goal is understanding how astrocyte-mediated synapse turnover affects the initiation and progression of various neurological disorders,” Professor Chung said. “It is intriguing to postulate that modulating astrocytic phagocytosis to restore synaptic connectivity may be a novel strategy in treating various brain disorders.”
This work was supported by the Samsung Science & Technology Foundation, the National Research Foundation of Korea, and the Korea Brain Research Institute basic research program.
Other contributors include Joon-Hyuk Lee and Se Young Lee, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST); Ji-young Kim, Hyoeun Lee and Hyungju Park; Research Group for Neurovascular Unit, Korea Brain Research Institute (KBRI); Seulgi Noh, and Ji Young Mun, Research Group for Neural Circuit, KBRI. Kim, Noh and Park are also affiliated with the Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST).
-Profile
Professor Won-Suk Chung
Department of Biological Sciences
Gliabiology Lab (https://www.kaistglia.org/)
KAIST
-Publication
"Astrocytes phagocytose adult hippocampal synapses for circuit homeostasis"
https://doi.org/10.1038/s41586-020-03060-3
2020.12.24 View 12556