OT
-
Deciphering Brain Somatic Mutations Associated with Alzheimer's Disease
Researchers have found a potential link between non-inherited somatic mutations in the brain and the progression of Alzheimer’s disease
Researchers have identified somatic mutations in the brain that could contribute to the development of Alzheimer’s disease (AD). Their findings were published in the journal Nature Communications last week.
Decades worth of research has identified inherited mutations that lead to early-onset familial AD. Inherited mutations, however, are behind at most half the cases of late onset sporadic AD, in which there is no family history of the disease. But the genetic factors causing the other half of these sporadic cases have been unclear.
Professor Jeong Ho Lee at the Graduate School of Medical Science and Engineering and colleagues analysed the DNA present in post-mortem hippocampal formations and in blood samples from people aged 70 to 96 with AD and age-matched controls. They specifically looked for non-inherited somatic mutations in their brains using high-depth whole exome sequencing.
The team developed a bioinformatics pipeline that enabled them to detect low-level brain somatic single nucleotide variations (SNVs) – mutations that involve the substitution of a single nucleotide with another nucleotide. Brain somatic SNVs have been reported on and accumulate throughout our lives and can sometimes be associated with a range of neurological diseases.
The number of somatic SNVs did not differ between individuals with AD and non-demented controls. Interestingly, somatic SNVs in AD brains arise about 4.8 times more slowly than in blood. When the team performed gene-set enrichment tests, 26.9 percent of the AD brain samples had pathogenic brain somatic SNVs known to be linked to hyperphosphorylation of tau proteins, which is one of major hallmarks of AD.
Then, they pinpointed a pathogenic SNV in the PIN1 gene, a cis/trans isomerase that balances phosphorylation in tau proteins, found in one AD patient’s brain. They found the mutation was 4.9 time more abundant in AT8-positive – a marker for hyper-phosphorylated tau proteins– neurons in the entorhinal cortex than the bulk hippocampal tissue. Furthermore, in a series of functional assays, they observed the mutation causing a loss of function in PIN1 and such haploinsufficiency increased the phosphorylation and aggregation of tau proteins.
“Our study provides new insights into the molecular genetic factors behind Alzheimer’s disease and other neurodegenerative diseases potentially linked to somatic mutations in the brain,” said Professor Lee.
The team is planning to expand their study to a larger cohort in order to establish stronger links between these brain somatic mutations and the pathogenesis of Alzheimer’s disease.
(Figure 1. Bioinformatic pipeline for detecting low-level brain somatic mutations in AD and non-AD.)
(Figure 2. Pathogenic brain somatic mutations associated with tau phosphorylation are significantly enriched in AD brains.)
(Figure 3. A pathogenic brain somatic mutation in PIN1 (c. 477 C>T) is a loss-of-function and related functional assays show its haploinsufficiency increases phosphorylation and aggregation of tau.)
2019.07.19 View 36300 -
Mathematical Modeling Makes a Breakthrough for a New CRSD Medication
PhD Candidate Dae Wook Kim (Left) and Professor Jae Kyoung Kim (Right)
- Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy -
Mathematicians’ new modeling has identified major sources of interspecies and inter-individual variations in the clinical efficacy of a clock-modulating drug: photosensitivity and PER2 level. This enabled precision medicine for circadian disruption.
A KAIST mathematics research team led by Professor Jae Kyoung Kim, in collaboration with Pfizer, applied a combination of mathematical modeling and simulation tools for circadian rhythms sleep disorders (CRSDs) to analyze the animal data generated by Pfizer. This study was reported in Molecular Systems Biology as the cover article on July 8.
Pharmaceutical companies have conducted extensive studies on animals to determine the candidacy of this new medication. However, the results of animal testing do not always translate to the same effects in human trials. Furthermore, even between humans, efficacy differs across individuals depending on an individual’s genetic and environmental factors, which require different treatment strategies.
To overcome these obstacles, KAIST mathematicians and their collaborators developed adaptive chronotherapeutics to identify precise dosing regimens that could restore normal circadian phase under different conditions.
A circadian rhythm is a 24-hour cycle in the physiological processes of living creatures, including humans. A biological clock in the hypothalamic suprachiasmatic nucleus in the human brain sets the time for various human behaviors such as sleep.
A disruption of the endogenous timekeeping system caused by changes in one’s life pattern leads to advanced or delayed sleep-wake cycle phase and a desynchronization between sleep-wake rhythms, resulting in CRSDs. To restore the normal timing of sleep, timing of the circadian clock could be adjusted pharmacologically.
Pfizer identified PF-670462, which can adjust the timing of circadian clock by inhibiting the core clock kinase of the circadian clock (CK1d/e). However, the efficacy of PF-670462 significantly differs between nocturnal mice and diurnal monkeys, whose sleeping times are opposite.
The research team discovered the source of such interspecies variations in drug response by performing thousands of virtual experiments using a mathematical model, which describes biochemical interactions among clock molecules and PF-670462. The result suggests that the effect of PF-670462 is reduced by light exposure in diurnal primates more than in nocturnal mice. This indicates that the strong counteracting effect of light must be considered in order to effectively regulate the circadian clock of diurnal humans using PF-670462.
Furthermore, the team also found the source of inter-patients variations in drug efficacy using virtual patients whose circadian clocks were disrupted due to various mutations. The degree of perturbation in the endogenous level of the core clock molecule PER2 affects the efficacy.
This explains why the clinical outcomes of clock-modulating drugs are highly variable and certain subtypes are unresponsive to treatment. Furthermore, this points out the limitations of current treatment strategies tailored to only the patient’s sleep and wake time but not to the molecular cause of sleep disorders.
PhD candidate Dae Wook Kim, who is the first author, said that this motivates the team to develop an adaptive chronotherapy, which identifies a personalized optimal dosing time of day by tracking the sleep-wake up time of patients via a wearable device and allows for a precision medicine approach for CRSDs.
Professor Jae Kyoung Kim said, "As a mathematician, I am excited to help enable the advancement of a new drug candidate, which can improve the lives of so many patients. I hope this result promotes more collaborations in this translational research.”
This research was supported by a Pfizer grant to KAIST (G01160179), the Human Frontiers Science Program Organization (RGY0063/2017), and a National Research Foundation (NRF) of Korea Grant (NRF-2016 RICIB 3008468 and NRF-2017-Fostering Core Leaders of the Future Basic Science Program/ Global Ph.D. Fellowship Program).
Figure 1. Interspecies and Inter-patients Variations in PF-670462 Efficacy
Figure 2. Journal Cover Page
Publication:
Dae Wook Kim, Cheng Chang, Xian Chen, Angela C Doran, Francois Gaudreault, Travis Wager, George J DeMarco, and Jae Kyoung Kim. 2019. Systems approach reveals photosensitivity and PER2 level as determinants of clock-modulator efficacy. Molecular Systems Biology. EMBO Press, Heidelberg, Germany, Vol. 15, Issue No. 7, Article, 16 pages. https://doi.org/10.15252/msb.20198838
Profile: Prof. Jae Kyoung Kim, PhD
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
Associate Professor
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dae Wook Kim, PhD Candidate
0308kdo@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
PhD Candidate
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr Daejeon 34141, Korea
Profile: Dr. Cheng Chang, PhD
cheng.chang@pfizer.com
Associate Director of Clinical Pharmacology
Clinical Pharmacology, Global Product Development
Pfizer
https://www.pfizer.com/ Groton 06340, USA
(END)
2019.07.09 View 35884 -
Deep Learning-Powered 'DeepEC' Helps Accurately Understand Enzyme Functions
(Figure: Overall scheme of DeepEC)
A deep learning-powered computational framework, ‘DeepEC,’ will allow the high-quality and high-throughput prediction of enzyme commission numbers, which is essential for the accurate understanding of enzyme functions.
A team of Dr. Jae Yong Ryu, Professor Hyun Uk Kim, and Distinguished Professor Sang Yup Lee at KAIST reported the computational framework powered by deep learning that predicts enzyme commission (EC) numbers with high precision in a high-throughput manner.
DeepEC takes a protein sequence as an input and accurately predicts EC numbers as an output. Enzymes are proteins that catalyze biochemical reactions and EC numbers consisting of four level numbers (i.e., a.b.c.d) indicate biochemical reactions. Thus, the identification of EC numbers is critical for accurately understanding enzyme functions and metabolism.
EC numbers are usually given to a protein sequence encoding an enzyme during a genome annotation procedure. Because of the importance of EC numbers, several EC number prediction tools have been developed, but they have room for further improvement with respect to computation time, precision, coverage, and the total size of the files needed for the EC number prediction.
DeepEC uses three convolutional neural networks (CNNs) as a major engine for the prediction of EC numbers, and also implements homology analysis for EC numbers if the three CNNs do not produce reliable EC numbers for a given protein sequence. DeepEC was developed by using a gold standard dataset covering 1,388,606 protein sequences and 4,669 EC numbers.
In particular, benchmarking studies of DeepEC and five other representative EC number prediction tools showed that DeepEC made the most precise and fastest predictions for EC numbers. DeepEC also required the smallest disk space for implementation, which makes it an ideal third-party software component.
Furthermore, DeepEC was the most sensitive in detecting enzymatic function loss as a result of mutations in domains/binding site residue of protein sequences; in this comparative analysis, all the domains or binding site residue were substituted with L-alanine residue in order to remove the protein function, which is known as the L-alanine scanning method.
This study was published online in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 20, 2019, entitled “Deep learning enables high-quality and high-throughput prediction of enzyme commission numbers.”
“DeepEC can be used as an independent tool and also as a third-party software component in combination with other computational platforms that examine metabolic reactions. DeepEC is freely available online,” said Professor Kim.
Distinguished Professor Lee said, “With DeepEC, it has become possible to process ever-increasing volumes of protein sequence data more efficiently and more accurately.”
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 of Korea. This work was also funded by the Bio & Medical Technology Development Program of the National Research Foundation of Korea funded by the Korean government, the Ministry of Science and ICT.
Profile:
-Professor Hyun Uk Kim (ehukim@kaist.ac.kr)
https://sites.google.com/view/ehukim
Department of Chemical and Biomolecular Engineering
-Distinguished Professor Sang Yup Lee (leesy@kaist.ac.kr)
Department of Chemical and Biomolecular Engineering
http://mbel.kaist.ac.kr
2019.07.09 View 37867 -
Wearable Robot 'WalkON Suit' Off to Cybathlon 2020
Standing upright and walking alone are very simple but noble motions that separate humans from many other creatures. Wearable and prosthetic technologies have emerged to augment human function in locomotion and manipulation. However, advances in wearable robot technology have been especially momentous to Byoung-Wook Kim, a triplegic for 22 years following a devastating car accident.
Kim rejoiced after standing upright and walking again by putting on the ‘WalkON Suit,’ the wearable robot developed by Professor Kyoungchul Kong’s team. Even more, Kim won third prize in the powered exoskeleton race at Cybathlon 2016, an international cyborg Olympics hosted by ETH Zurich.
Now Kim and Professor Kong’s team are all geared up for the Cybathlon Championship 2020. Professor Kong and his startup, Angel Robotics, held a kickoff ceremony for Cybathlon 2020 at KAIST on June 24. The 2020 championship will take place in Switzerland.
Only pilots with complete paralysis of the legs resulting from spinal cord injuries are eligible to participate in the Cybathlon, which takes place every four years. Pilots compete against each other while completing everyday tasks using technical assistance systems in six different disciplines: a brain-computer interface race, a functional electrical stimulation bike race, a powered arm prosthesis race, a powered leg prosthesis race, a powered exoskeleton race, and a powered wheelchair race. The 2016 championship drew 66 pilots from 56 teams representing 25 countries.
In the powered exoskeleton race, pilots complete everyday activities such as getting up from a sofa and overcoming obstacles such as stairs, ramps, or slopes and up to four pilots compete simultaneously on tracks to solve six tasks; and the pilot that solves the most tasks in the least amount of time wins the race.
(Kim, a triplegic for 22 years demonstrates walking and climbing the stairs (below photo) wearing the WalkOn Suit during the media day on June 21 at KAIST.)
Kim, who demonstrated walking and climbing the stairs wearing the WalkON Suit during the media day for the Cybathlon 2020 kickoff ceremony on June 21 at KAIST, said, “I have been confined to a wheelchair for more than 20 years. I am used to it so I feel like the wheelchair is one of my body parts. Actually, I don’t feel any big difficulties in doing everyday tasks in wheelchair. But whenever I face the fact that I will never be able to stand up with my own two legs again, I am so devastated.” He continued, “I still remember the day when I stood up with my own two legs by myself after 22 years. It was beyond description.”
The market for wearable robots, especially for exoskeleton robots, is continuing to grow as the aging population has been a major challenge in almost every advanced country. The global market for these robots expects to see annual growth of 41.2% to 8.3 billion US dollars by 2025. Healthcare wearable robots for the elderly and rehabilitation take up the half of the market share followed by wearable robots for industrial and defense purposes.
Professor Kong from the Department of Mechanical Engineering and his colleagues have developed two wearable robot systems in 2014: The "WalkON Suit" for complete paraplegics and “Angel Suit” for those with partial impairment in walking ability such as the elderly and rehabilitation patients.
Professor Kong said after 15 years of basic research, the team is now able to develop its own distinct technologies. He said their robots are powered by non-resistant precision drives with algorithms recognizing the user’s moving intention. Incorporated with prosthetic devices technology from the Severance Rehabilitation Hospital, their control technology has led to the production of a customizable robot suit optimized for each user’s physical condition.
The WalkON Suit, which boasts a maximum force of 250 Nm and maximum rotation speed of 45 RPM, gives the user high-energy efficiency modeled after the physiology of the human leg. It allows users to walk on flat ground and down stairs, climb up and down inclines, and sit and lie down. Currently the battery lasts five to six hours for locomotion and the approximate 25 kg of robot weight still remains a technical challenge to upgrade.
Professor Kong’s team has grafted AR glass technology into the WalkOn Suit that one of his pilots put on for the torch relay of the PyongChang Paralympics in 2018. His team is now upgrading the WalkON Suit 4.0 for next year’s competition. Severance Rehabilitation Hospital will help the seven pilots with their training.
Professor Kong said his goal is to make robots that can make people with disabilities much more independent. He stressed, “Wearable robots should be designed for each single user. We provide a very good graphical user interface so that we can design, check, and also verify our optimized design for users’ best performance.”
(Seven pilots and Professor Kong (fifth from left in second row) pose with guests who joined the Cybathlon 2020 kickoff ceremony. President Shin (fifth from right) made a congratulatory remarks during the ceremony.)
2019.06.25 View 41188 -
Efficiently Producing Fatty Acids and Biofuels from Glucose
Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.
The newly developed strain, created by Distinguished Professor Sang Yup Lee and his team, showed the highest efficiency in producing fatty acids and biodiesels ever reported. It will be expected to serve as a new platform to sustainably produce a wide array of fatty acid-based products from glucose and other carbon substrates.
Fossil fuels, which have long been energy resources for our daily lives, are now facing serious challenges: depletion of their reserves and their role in global warming. The production of sustainable bio-based renewable energy has emerged as an essential alternative and many studies to replace fossil fuels are underway. One of the representative examples is biodiesel. Currently, it is mainly being produced through the transesterification of vegetable oils or animal fats.
The research team engineered oleaginous microorganisms, Rhodococcus opacus, to produce fatty acids and their derivatives that can be used as biodiesel from glucose, one of the most abundant and cheap sugars derived from non-edible biomass.
Professor Lee’s team has already engineered Escherichia coli to produce short-chain hydrocarbons, which can be used as gasoline (published in Nature as the cover paper in 2013). However, the production efficiency of the short-chain hydrocarbons using E. coli (0.58 g/L) fell short of the levels required for commercialization.
To overcome these issues, the team employed oil-accumulating Rhodococcus opacus as a host strain in this study. First, the team optimized the cultivation conditions of Rhodococcus opacus to maximize the accumulation of oil (triacylglycerol), which serves as a precursor for the biosynthesis of fatty acids and their derivatives. Then, they systematically analyzed the metabolism of the strain and redesigned it to enable higher levels of fatty acids and two kinds of fatty acid-derived biodiesels (fatty acid ethyl esters and long-chain hydrocarbons) to be produced.
They found that the resulting strains produced 50.2, 21.3, and 5.2 g/L of fatty acids, fatty acid ethyl esters, and long-chain hydrocarbons, respectively. These are all the highest concentrations ever reported by microbial fermentations. It is expected that these strains can contribute to the future industrialization of microbial-based biodiesel production.
“This technology creates fatty acids and biodiesel with high efficiency by utilizing lignocellulose, one of the most abundant resources on the Earth, without depending on fossil fuels and vegetable or animal oils. This will provide new opportunities for oil and petroleum industries, which have long relied on fossil fuels, to turn to sustainable and eco-friendly biotechnologies,” said Professor Lee.
This paper titled “Engineering of an oleaginous bacterium for the production of fatty acids and fuels” was published in Nature Chemical Biology on June 17.
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 (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557).
(Figure: Metabolic engineering for the production of free fatty acids (FFAs), fatty acid ethyl esters (FAEEs), and long-chain hydrocarbons (LCHCs) in Rhodococcus opacus PD630. Researchers have presented a new strategy for efficiently producing fatty acids and biofuels that can transform glucose and oleaginous microorganisms into microbial diesel fuel, with one-step direct fermentative production.)
# # #
Source:
Hye Mi Kim, Tong Un Chae, So Young Choi, Won Jun Kim and Sang Yup Lee. Engineering of an oleaginous bacterium for the production of fatty acids and fuels. Nature Chemical Biology ( https://www.nature.com/nchembio/ ) DOI: 10.1038/s41589-019-0295-5
Profile
Dr. Sang Yup Lee
leesy@kaist.ac.kr
Distinguished Professor at the Department of Chemical and Biomolecular Engineering
KAIST
2019.06.19 View 49721 -
Engineered Microbial Production of Grape Flavoring
(Image 1: Engineered bacteria that produce grape flavoring.)
Researchers report a microbial method for producing an artificial grape flavor. Methyl anthranilate (MANT) is a common grape flavoring and odorant compound currently produced through a petroleum-based process that uses large volumes of toxic acid catalysts.
Professor Sang-Yup Lee’s team at the Department of Chemical and Biomolecular Engineering demonstrated production of MANT, a naturally occurring compound, via engineered bacteria. The authors engineered strains of Escherichia coli and Corynebacetrium glutamicum to produce MANT through a plant-based engineered metabolic pathway.
The authors tuned the bacterial metabolic pathway by optimizing the levels of AAMT1, the key enzyme in the process. To maximize production of MANT, the authors tested six strategies, including increasing the supply of a precursor compound and enhancing the availability of a co-substrate. The most productive strategy proved to be a two-phase extractive culture, in which MANT was extracted into a solvent. This strategy produced MANT on the scale of 4.47 to 5.74 grams per liter, a significant amount, considering that engineered microbes produce most natural products at a scale of milligrams or micrograms per liter.
According to the authors, the results suggest that MANT and other related molecules produced through industrial processes can be produced at scale by engineered microbes in a manner that would allow them to be marketed as natural one, instead of artificial one.
This study, featured at the Proceeding of the National Academy of Sciences of the USA on May 13, was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT.
(Image 2. Overview of the strategies applied for the microbial production of grape flavoring.)
2019.05.15 View 55727 -
The First Award for Concept Cars, Future Mobility of the Year
KAIST will host an award to recognize the most visionary and inspiring concept cars of the year.
The ‘Future Mobility of the Year (FMOTY)’ Awards recognize concept cars that have made outstanding contributions to future mobility. The first awards ceremony will take place in Korea in March 2019.
The awards will be given to concept cars that exhibit innovative services and practical transportation technology in three categories: private mobility, public and commercial mobility, and personal mobility.
To ensure a fair judging process, the contest invited influential and eminent journalists in the automotive field. They will evaluate the social values and innovative contributions of the concept cars that will pave the way for next-generation transportation.
Concept cars have been neglected in existing automobile awards, such as the ‘Car of the Year’ because they have been considered experimental prototypes only built for showcasing a new vision for the quite far future.
The FMOTY Awards will brings concept cars back into the spotlight and showcase the best ideas and social values of mind-blowing concept cars.
Among 45 concept cars, fifteen candidates were selected as finalists after the initial screening that took place over the last three months: including models from Audi, BMW, Mercedes-Benz, Peugeot, Porsche, Renault, Toyota, Volkswagen, and Volvo. The winners will be announced and awarded in Seoul on March 28th.
Kyung-soo Kim, Dean of the Cho Chun Shik Graduate School of Green Transportation which organizes the award said, “As the automobile industry undergoes an era of transformation, it is crucial to recognize the efforts of automobile companies who are making attempts to create novel forms of mobility. That is why we launched the FMOTY Awards, hoping to add a future-oriented spirit to the existing awards that consider finished vehicles only. By selecting the best concept car, the FMOTY Awards will expand public attention from the present to the future.”
Details can be found on the official website of FMOTY ( www.fmoty.org), where photos of the finalists are also available for download ( http://bitly.kr/JTUUp).
Figure 1. Finalists for the 'Future Mobility of the Year'
2019.02.13 View 7871 -
Noninvasive Light-Sensitive Recombinase for Deep Brain Genetic Manipulation
A KAIST team presented a noninvasive light-sensitive photoactivatable recombinase suitable for genetic manipulation in vivo. The highly light-sensitive property of photoactivatable Flp recombinase will be ideal for controlling genetic manipulation in deep mouse brain regions by illumination with a noninvasive light-emitting diode. This easy-to-use optogenetic module made by Professor Won Do Heo and his team will provide a side-effect free and expandable genetic manipulation tool for neuroscience research.
Spatiotemporal control of gene expression has been acclaimed as a valuable strategy for identifying functions of genes with complex neural circuits. Studies of complex brain functions require highly sophisticated and robust technologies that enable specific labeling and rapid genetic modification in live animals. A number of approaches for controlling the activity of proteins or expression of genes in a spatiotemporal manner using light, small molecules, hormones, and peptides have been developed for manipulating intact circuits or functions.
Among them, recombination-employing, chemically inducible systems are the most commonly used in vivo gene-modification systems. Other approaches include selective or conditional Cre-activation systems within subsets of green fluorescent protein-expressing cells or dual-promoter-driven intersectional populations of cells.
However, these methods are limited by the considerable time and effort required to establish knock-in mouse lines and by constraints on spatiotemporal control, which relies on a limited set of available genetic promoters and transgenic mouse resources.
Beyond these constraints, optogenetic approaches allow the activity of genetically defined neurons in the mouse brain to be controlled with high spatiotemporal resolution. However, an optogenetic module for gene-manipulation capable of revealing the spatiotemporal functions of specific target genes in the mouse brain has remained a challenge.
In the study published at Nature Communication on Jan. 18, the team featured photoactivatable Flp recombinase by searching out split sites of Flp recombinase that were not previously identified, being capable of reconstitution to be active. The team validated the highly light-sensitive, efficient performance of photoactivatable Flp recombinase through precise light targeting by showing transgene expression within anatomically confined mouse brain regions.
The concept of local genetic labeling presented here suggests a new approach for genetically identifying subpopulations of cells defined by the spatial and temporal characteristics of light delivery. To date, an optogenetic module for gene-manipulation capable of revealing spatiotemporal functions of specific target genes in the mouse brain has remained out of reach and no such light-inducible Flp system has been developed. Accordingly, the team sought to develop a photoactivatable Flp recombinase that takes full advantage of the high spatiotemporal control offered by light stimulation.
This activation through noninvasive light illumination deep inside the brain is advantageous in that it avoids chemical or optic fiber implantation-mediated side effects, such as off-target cytotoxicity or physical lesions that might influence animal physiology or behaviors. The technique provides expandable utilities for transgene expression systems upon Flp recombinase activity in vivo, by designing a viral vector for minimal leaky expression influenced by viral nascent promoters.
The team demonstrated the utility of PA-Flp as a noninvasive in vivo optogenetic manipulation tool for use in the mouse brain, even applicable for deep brain structures as it can reach the hippocampus or medial septum using external LED light illumination.
The study is the result of five years of research by Professor Heo, who has led the bio-imaging and optogenetics fields by developing his own bio-imaging and optogenetics technologies. “It will be a great advantage to control specific gene expression desired by LEDs with little physical and chemical stimulation that can affect the physiological phenomenon in living animals,” he explained.
2019.01.22 View 7451 -
From Concept to Reality: Changing Color of Light Using a Spatiotemporal Boundary
(from left: Professor Bumki Min, PhD candidate Jaehyeon Son and PhD Kanghee Lee)
A KAIST team developed an optical technique to change the color (frequency) of light using a spatiotemporal boundary. The research focuses on realizing a spatiotemporal boundary with a much higher degree of freedom than the results of previous studies by fabricating a thin metal structure on a semiconductor surface. Such a spatiotemporal boundary is expected to be applicable to an ultra-thin film type optical device capable of changing the color of light.
The optical frequency conversion device plays a key role in precision measurement and communication technology, and the device has been developed mainly based on optical nonlinearity.
If the intensity of light is very strong, the optical medium responds nonlinearly so the nonlinear optical phenomena, such as frequency doubling or frequency mixing, can be observed. Such optical nonlinear phenomena are realized usually by the interaction between a high-intensity laser and a nonlinear medium.
As an alternative method frequency conversion is observed by temporally modifying the optical properties of the medium through which light travels using an external stimulus. Since frequency conversion in this way can be observed even in weak light, such a technique could be particularly useful in communication technology.
However, rapid optical property modification of the medium by an external stimulus and subsequent light frequency conversion techniques have been researched only in the pertubative regime, and it has been difficult to realize these theoretical results in practical applications.
To realize such a conceptual idea, Professor Bumki Min from the Department of Mechanical Engineering and his team collaborated with Professor Wonju Jeon from the Department of Mechanical Engineering and Professor Fabian Rotermund from the Department of Physics. They developed an artificial optical material (metamaterial) by arranging a metal microstructure that mimics an atomic structure and succeeded in creating a spatiotemporal boundary by changing the optical property of the artificial material abruptly.
While previous studies only slightly modified the refractive index of the medium, this study provided a spatiotemporal boundary as a platform for freely designing and changing the spectral properties of the medium. Using this, the research team developed a device that can control the frequency of light to a large degree.
The research team said a spatiotemporal boundary, which was only conceptually considered in previous research and realized in the pertubative regime, was developed as a step that can be realized and applied.
Professor Min said, “The frequency conversion of light becomes designable and predictable, so our research could be applied in many optical applications. This research will present a new direction for time-variant media research projects in the field of optics.”
This research, led by PhD Kanghee Lee and PhD candidate Jaehyeon Son, was published online in Nature Photonics on October 8, 2018.
This work was supported by the National Research Foundation of Korea (NRF) through the government of Korea. The work was also supported by the Center for Advanced Meta-Materials (CAMM) funded by the Korea Government (MSIP) as the Global Frontier Project (NRF-2014M3A6B3063709).
Figure 1. The frequency conversion process of light using a spatiotemporal boundary.
Figure 2. The complex amplitude of light at the converted frequency with the variation of a spatiotemporal boundary.
2018.11.29 View 8304 -
Permanent, Wireless Self-charging System Using NIR Band
(Professor Jung-Yong Lee from the Graduate School of Energy, Environment, Water and Sustainability)
As wearable devices are emerging, there are numerous studies on wireless charging systems. Here, a KAIST research team has developed a permanent, wireless self-charging platform for low-power wearable electronics by converting near-infrared (NIR) band irradiation to electrical energy. This novel technology can be applied to flexible, wearable charging systems without needing any attachments.
Colloidal-quantum-dots (CQDs) are promising materials for manufacturing semiconductors; in particular, PbS-based CQDs have facile optical tunability from the visible to infrared wavelength region. Hence, they can be applied to various devices, such as lighting, photovoltaics (PVs), and photodetectors.
Continuous research on CQD-based optoelectronic devices has increased their power conversion efficiency (PCE) to 12%; however, applicable fields have not yet been found for them. Meanwhile, wearable electronic devices commonly face the problem of inconvenient charging systems because users have to constantly charge batteries attached to an energy source.
A joint team led by Professor Jung-Yong Lee from the Graduate School of Energy, Environment, Water and Sustainability and Jang Wok Choi from Seoul National University decided to apply CQD PVs, which have high quantum efficiency in NIR band to self-charging systems on wearable devices.
They employed a stable and efficient NIR energy conversion strategy. The system was comprised of a PbS CQD-based PV module, a flexible interdigitated lithium-ion battery, and various types of NIR-transparent films.
The team removed the existing battery from the already commercialized wearable healthcare bracelet and replaced it with the proposed self-charging system. They confirmed that the system can be applied to a low power wearable device via the NIR band.
There have been numerous platforms using solar irradiation, but the newly developed platform has more advantages because it allows conventional devices to be much more comfortable to wear and charged easily in everyday life using various irradiation sources for constant charging.
With this aspect, the proposed platform facilitates more flexible designs, which are the important component for actual commercialization. It also secures higher photostability and efficient than existing structures.
Professor Lee said, “By using the NIR band, we proposed a new approach to solve charging system issues of wearable devices. I believe that this platform will be a novel platform for energy conversion and that its application can be further extended to various fields, including mobiles, IoTs, and drones.”
This research, led by PhD Se-Woong Baek and M.S. candidate Jungmin Cho, was published in Advanced Materials on May 11.
Figure 1. a) Conceptual NIR-driven self-charging system including a flexible CQD PVs module and an interdigitatedly structured LIB. b) Photographic images of a conventional wearable healthcare bracelet and a self-charging system-integrated wearable device.
Figure 2. Illustration of the CQD PVs structure and performance of the wireless self-charging platform.
2018.10.08 View 8600 -
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 10990 -
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 9528