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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 12064 -
Attachable Skin Monitors that Wick the Sweat Away
- A silicone membrane for wearable devices is more comfortable and breathable thanks to better-sized pores made with the help of citric acid crystals. -
A new preparation technique fabricates thin, silicone-based patches that rapidly wick water away from the skin. The technique could reduce the redness and itching caused by wearable biosensors that trap sweat beneath them. The technique was developed by bioengineer and professor Young-Ho Cho and his colleagues at KAIST and reported in the journal Scientific Reports last month.
“Wearable bioelectronics are becoming more attractive for the day-to-day monitoring of biological compounds found in sweat, like hormones or glucose, as well as body temperature, heart rate, and energy expenditure,” Professor Cho explained. “But currently available materials can cause skin irritation, so scientists are looking for ways to improve them,” he added.
Attachable biosensors often use a silicone-based compound called polydimethylsiloxane (PDMS), as it has a relatively high water vapour transmission rate compared to other materials. Still, this rate is only two-thirds that of skin’s water evaporation rate, meaning sweat still gets trapped underneath it.
Current fabrication approaches mix PDMS with beads or solutes, such as sugars or salts, and then remove them to leave pores in their place. Another technique uses gas to form pores in the material. Each technique has its disadvantages, from being expensive and complex to leaving pores of different sizes.
A team of researchers led by Professor Cho from the KAIST Department of Bio and Brain Engineering was able to form small, uniform pores by crystallizing citric acid in PDMS and then removing the crystals using ethanol. The approach is significantly cheaper than using beads, and leads to 93.2% smaller and 425% more uniformly-sized pores compared to using sugar. Importantly, the membrane transmits water vapour 2.2 times faster than human skin.
The team tested their membrane on human skin for seven days and found that it caused only minor redness and no itching, whereas a non-porous PDMS membrane did.
Professor Cho said, “Our method could be used to fabricate porous PDMS membranes for skin-attachable devices used for daily monitoring of physiological signals.”
“We next plan to modify our membrane so it can be more readily attached to and removed from skin,” he added.
This work was supported by the Ministry of Trade, Industry and Energy (MOTIE) of Korea under the Alchemist Project.
Image description:
Smaller, more uniformly-sized pores are made in the PDMS membrane by mixing PDMS, toluene, citric acid, and ethanol. Toluene dilutes PDMS so it can easily mix with the other two constituents. Toluene and ethanol are then evaporated, which causes the citric acid to crystallize within the PDMS material. The mixture is placed in a mould where it solidifies into a thin film. The crystals are then removed using ethanol, leaving pores in their place.
Image credit:
Professor Young-Ho Cho, KAIST
Image usage restrictions:
News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only.
Publication:
Yoon, S, et al. (2021) Wearable porous PDMS layer of high moisture permeability for skin trouble reduction. Scientific Reports 11, Article No. 938. Available online at https://doi.org/10.1038/s41598-020-78580-z
Profile:
Young-Ho Cho, Ph.D
Professor
mems@kaist.ac.kr
https://mems.kaist.ac.kr
NanoSentuating Systems Laboratory
Department of Bio and Brain Engineering
https://kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
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2021.02.22 View 12926 -
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 10642 -
Professor Bumjoon Kim Named Scientist of the Month
Professor Bumjoon Kim from the Department of Chemical and Biomolecular Engineering won January’s Scientist of the Month Award presented by the Ministry of Science and ICT (MSIT) and the National Research Foundation of Korea (NRF) on January 6. Professor Kim also received 10 million won in prize money.
Professor Kim was recognized for his research in the field of fuel cells. Since the first paper on fuel cells was published in 1839 by the German chemist Friedrich Schonbein, there has been an increase in the number of fields in which fuel cells are used, including national defense, aerospace engineering, and autonomous vehicles.
Professor Kim developed carbonized block copolymer particles with high durability and a high-performance fuel cell. Block copolymers are two different polymers cross-linked into a chain structure. Various nanostructures can be made effectively by using the attractive and repulsive forces between the chains.
Professor Kim used the membrane emulsification technique, employing a high-performance separation membrane to develop a platform that makes the mass production of highly durable carbonized particles possible, which he then used to develop high-performance energy devices like fuel cells.
The carbonized particles designed by Professor Kim and his research team were used to create the world’s more durable fuel cells that boast outstanding performance while using only five percent of the costly platinum needed for existing commercialized products.
The team’s research results were published in the Journal of the American Chemical Society and Energy Environmental Science in May and July of last year.
“We have developed a fuel cell that ticks all the boxes including performance, durability, and cost,” said Professor Kim. “Related techniques will not be limited to fuel cells, but could also be applied to the development of various energy devices like solar cells and secondary cells,” he added.
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2021.01.22 View 11629 -
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 11914 -
A Biological Strategy Reveals How Efficient Brain Circuitry Develops Spontaneously
- A KAIST team’s mathematical modelling shows that the topographic tiling of cortical maps originates from bottom-up projections from the periphery. -
Researchers have explained how the regularly structured topographic maps in the visual cortex of the brain could arise spontaneously to efficiently process visual information. This research provides a new framework for understanding functional architectures in the visual cortex during early developmental stages.
A KAIST research team led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering has demonstrated that the orthogonal organization of retinal mosaics in the periphery is mirrored onto the primary visual cortex and initiates the clustered topography of higher visual areas in the brain.
This new finding provides advanced insights into the mechanisms underlying a biological strategy of brain circuitry for the efficient tiling of sensory modules. The study was published in Cell Reports on January 5.
In higher mammals, the primary visual cortex is organized into various functional maps for neural tuning such as ocular dominance, orientation selectivity, and spatial frequency selectivity. Correlations between the topographies of different maps have been observed, implying their systematic organizations for the efficient tiling of sensory modules across cortical areas.
These observations have suggested that a common principle for developing individual functional maps may exist. However, it has remained unclear how such topographical organizations could arise spontaneously in the primary visual cortex of various species.
The research team found that the orthogonal organization in the primary visual cortex of the brain originates from the spatial organization in bottom-up feedforward projections. The team showed that an orthogonal relationship among sensory modules already exists in the retinal mosaics, and that this is mirrored onto the primary visual cortex to initiate the clustered topography.
By analyzing the retinal ganglion cell mosaics data in cats and monkeys, the researchers found that the structure of ON-OFF feedforward afferents is organized into a topographic tiling, analogous to the orthogonal intersection of cortical tuning maps.
Furthermore, the team’s analysis of previously published data collected on cats also showed that the ocular dominance, orientation selectivity, and spatial frequency selectivity in the primary visual cortex are correlated with the spatial profiles of the retinal inputs, implying that efficient tiling of cortical domains can originate from the regularly structured retinal patterns.
Professor Paik said, “Our study suggests that the structure of the periphery with simple feedforward wiring can provide the basis for a mechanism by which the early visual circuitry is assembled.”
He continued, “This is the first report that spatially organized retinal inputs from the periphery provide a common blueprint for multi-modal sensory modules in the visual cortex during the early developmental stages. Our findings would make a significant impact on our understanding the developmental strategy of brain circuitry for efficient sensory information processing.”
This work was supported by the National Research Foundation of Korea (NRF).
Image credit: Professor Se-Bum Paik, KAIST
Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of news coverage of this paper only.
Publication:
Song, M, et al. (2021) Projection of orthogonal tiling from the retina to the visual cortex. Cell Reports 34, 108581. Available online at https://doi.org/10.1016/j.celrep.2020.108581
Profile:
Se-Bum Paik, Ph.D
Assistant Professor
sbpaik@kaist.ac.kr
http://vs.kaist.ac.kr/
VSNN Laboratory
Department of Bio and Brain Engineering
Program of Brain and Cognitive Engineering
http://kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST) Daejeon, Republic of Korea
Profile:
Min Song
Ph.D. Candidate
night@kaist.ac.kr
Program of Brain and Cognitive Engineering
Profile:
Jaeson Jang, Ph.D.
Researcher
jaesonjang@kaist.ac.kr
Department of Bio and Brain Engineering, KAIST
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2021.01.14 View 7873 -
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.”
(END)
2021.01.13 View 6718 -
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 11692 -
DeepTFactor Predicts Transcription Factors
A deep learning-based tool predicts transcription factors using protein sequences as inputs
A joint research team from KAIST and UCSD has developed a deep neural network named DeepTFactor that predicts transcription factors from protein sequences. DeepTFactor will serve as a useful tool for understanding the regulatory systems of organisms, accelerating the use of deep learning for solving biological problems.
A transcription factor is a protein that specifically binds to DNA sequences to control the transcription initiation. Analyzing transcriptional regulation enables the understanding of how organisms control gene expression in response to genetic or environmental changes. In this regard, finding the transcription factor of an organism is the first step in the analysis of the transcriptional regulatory system of an organism.
Previously, transcription factors have been predicted by analyzing sequence homology with already characterized transcription factors or by data-driven approaches such as machine learning. Conventional machine learning models require a rigorous feature selection process that relies on domain expertise such as calculating the physicochemical properties of molecules or analyzing the homology of biological sequences. Meanwhile, deep learning can inherently learn latent features for the specific task.
A joint research team comprised of Ph.D. candidate Gi Bae Kim and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST, and Ye Gao and Professor Bernhard O. Palsson of the Department of Biochemical Engineering at UCSD reported a deep learning-based tool for the prediction of transcription factors. Their research paper “DeepTFactor: A deep learning-based tool for the prediction of transcription factors” was published online in PNAS.
Their article reports the development of DeepTFactor, a deep learning-based tool that predicts whether a given protein sequence is a transcription factor using three parallel convolutional neural networks. The joint research team predicted 332 transcription factors of Escherichia coli K-12 MG1655 using DeepTFactor and the performance of DeepTFactor by experimentally confirming the genome-wide binding sites of three predicted transcription factors (YqhC, YiaU, and YahB).
The joint research team further used a saliency method to understand the reasoning process of DeepTFactor. The researchers confirmed that even though information on the DNA binding domains of the transcription factor was not explicitly given the training process, DeepTFactor implicitly learned and used them for prediction. Unlike previous transcription factor prediction tools that were developed only for protein sequences of specific organisms, DeepTFactor is expected to be used in the analysis of the transcription systems of all organisms at a high level of performance.
Distinguished Professor Sang Yup Lee said, “DeepTFactor can be used to discover unknown transcription factors from numerous protein sequences that have not yet been characterized. It is expected that DeepTFactor will serve as an important tool for analyzing the regulatory systems of organisms of interest.”
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.
-Publication
Gi Bae Kim, Ye Gao, Bernhard O. Palsson, and Sang Yup Lee. DeepTFactor: A deep learning-based tool for the prediction of transcription factors. (https://doi.org/10.1073/pnas202117118)
-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
2021.01.05 View 9432 -
Extremely Stable Perovskite Nanoparticles Films for Next-Generation Displays
Researchers have reported an extremely stable cross-linked perovskite nanoparticle that maintains a high photoluminescence quantum yield (PLQY) for 1.5 years in air and harsh liquid environments. This stable material’s design strategies, which addressed one of the most critical problems limiting their practical application, provide a breakthrough for the commercialization of perovskite nanoparticles in next-generation displays and bio-related applications.
According to the research team led by Professor Byeong-Soo Bae, their development can survive in severe environments such as water, various polar solvents, and high temperature with high humidity without additional encapsulation. This development is expected to enable perovskite nanoparticles to be applied to high color purity display applications as a practical color converting material. This result was published as the inside front cover article in Advanced Materials.
Perovskites, which consist of organics, metals, and halogen elements, have emerged as key elements in various optoelectronic applications. The power conversion efficiency of photovoltaic cells based on perovskites light absorbers has been rapidly increased. Perovskites are also great promise as a light emitter in display applications because of their low material cost, facile wavelength tunability, high (PLQY), very narrow emission band width, and wider color gamut than inorganic semiconducting nanocrystals and organic emitters. Thanks to these advantages, perovskites have been identified as a key color-converting material for next-generation high color-purity displays. In particular, perovskites are the only luminescence material that meets Rec. 2020 which is a new color standard in display industry.
However, perovskites are very unstable against heat, moisture, and light, which makes them almost impossible to use in practical applications. To solve these problems, many researchers have attempted to physically prevent perovskites from coming into contact with water molecules by passivating the perovskite grain and nanoparticle surfaces with organic ligands or inorganic shell materials, or by fabricating perovskite-polymer nanocomposites. These methods require complex processes and have limited stability in ambient air and water. Furthermore, stable perovskite nanoparticles in the various chemical environments and high temperatures with high humidity have not been reported yet.
The research team in collaboration with Seoul National University develops siloxane-encapsulated perovskite nanoparticle composite films. Here, perovskite nanoparticles are chemically crosslinked with thermally stable siloxane molecules, thereby significantly improving the stability of the perovskite nanoparticles without the need for any additional protecting layer.
Siloxane-encapsulated perovskite nanoparticle composite films exhibited a high PLQY (> 70%) value, which can be maintained over 600 days in water, various chemicals (alcohol, strong acidic and basic solutions), and high temperatures with high humidity (85℃/85%). The research team investigated the mechanisms impacting the chemical crosslinking and water molecule-induced stabilization of perovskite nanoparticles through various photo-physical analysis and density-functional theory calculation.
The research team confirmed that displays based on their siloxane-perovskite nanoparticle composite films exhibited higher PLQY and a wider color gamut than those of Cd-based quantum dots and demonstrated perfect color converting properties on commercial mobile phone screens. Unlike what was commonly believed in the halide perovskite field, the composite films showed excellent bio-compatibility because the siloxane matrix prevents the toxicity of Pb in perovskite nanoparticle.
By using this technology, the instability of perovskite materials, which is the biggest challenge for practical applications, is greatly improved through simple encapsulation method.
“Perovskite nanoparticle is the only photoluminescent material that can meet the next generation display color standard. Nevertheless, there has been reluctant to commercialize it due to its moisture vulnerability. The newly developed siloxane encapsulation technology will trigger more research on perovskite nanoparticles as color conversion materials and will accelerate early commercialization,” Professor Bae said.
This work was supported by the Wearable Platform Materials Technology Center (WMC) of the Engineering Research Center (ERC) Project, and the Leadership Research Program funded by the National Research Foundation of Korea.
-Publication:
Junho Jang, Young-Hoon Kim, Sunjoon Park, Dongsuk Yoo, Hyunjin Cho, Jinhyeong Jang, Han Beom Jeong, Hyunhwan Lee, Jong Min Yuk, Chan Beum Park, Duk Young Jeon, Yong-Hyun Kim, Byeong-Soo Bae, and Tae-Woo Lee. “Extremely Stable Luminescent Crosslinked Perovskite Nanoparticles under Harsh Environments over 1.5 Years” Advanced Materials, 2020, 2005255. https://doi.org/10.1002/adma.202005255.
Link to download the full-text paper:
https://onlinelibrary.wiley.com/doi/10.1002/adma.202005255
-Profile: Prof. Byeong-Soo Bae (Corresponding author)
bsbae@kaist.ac.kr
Lab. of Optical Materials & Coating
Department of Materials Science and Engineering
Korea Advanced Institute of Science and Technology (KAIST)
2020.12.29 View 13057 -
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 11567 -
Electrosprayed Micro Droplets Help Kill Bacteria and Viruses
With COVID-19 raging around the globe, researchers are doubling down on methods for developing diverse antimicrobial technologies that could be effective in killing a virus, but harmless to humans and the environment.
A recent study by a KAIST research team will be one of the responses to such efforts. Professor Seung Seob Lee and Dr. Ji-hun Jeong from the Department of Mechanical Engineering developed a harmless air sterilization prototype featuring electrosprayed water from a polymer micro-nozzle array. This study is one of the projects being supported by the KAIST New Deal R&D Initiative in response to COVID-19. Their study was reported in Polymer.
The electrosprayed microdroplets encapsulate reactive oxygen species such as hydroxyl radicals, superoxides that are known to have an antimicrobial function. The encapsulation prolongs the life of reactive oxygen species, which enable the droplets to perform their antimicrobial function effectively. Prior research has already proven the antimicrobial and encapsulation effects of electrosprayed droplets.
Despite its potential for antimicrobial applications, electrosprayed water generally operates under an electrical discharge condition, which can generate ozone. The inhalation of ozone is known to cause damage to the respiratory system of humans. Another technical barrier for electrospraying is the low flow rate problem. Since electrospraying exhibits the dependence of droplet size on the flow rate, there is a limit for the amount of water microdroplets a single nozzle can produce.
With this in mind, the research team developed a dielectric polymer micro-nozzle array to perform the multiplexed electrospraying of water without electrical discharge. The polymer micro-nozzle array was fabricated using the MEMS (Micro Electro-Mechanical System) process. According to the research team, the nozzle can carry five to 19 micro-nozzles depending on the required application.
The high aspect ratio of the micro-nozzle and an in-plane extractor were proposed to concentrate the electric field at the tip of the micro-nozzle, which prevents the electrical discharge caused by the high surface tension of water. A micro-pillar array with a hydrophobic coating around the micro-nozzle was also proposed to prevent the wetting of the micro-nozzle array.
The polymer micro-nozzle array performed in steady cone jet mode without electrical discharge as confirmed by high-speed imaging and nanosecond pulsed imaging. The water microdroplets were measured to be in the range of six to 10 μm and displayed an antimicrobial effect on Escherichia coli and Staphylococcus aureus.
Professor Lee said, “We believe that this research can be applied to air conditioning products in areas that require antimicrobial and humidifying functions.”
Publication:
Jeong, J. H., et al. (2020) Polymer micro-atomizer for water electrospray in the cone jet mode. Polymer. Vol. No. 194, 122405. Available online at https://doi.org/10.1016/j.polymer.2020.122405
Profile: Seung Seob Lee, Ph.D.
sslee97@kaist.ac.kr
http://mmst.kaist.ac.kr/
Professor
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Ji-hun Jeong, Ph.D.
jiuni6022@kaist.ac.kr
Postdoctoral researcher
Department of Mechanical Engineering (ME)
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.kr
Daejeon 34141, Korea
(END)
2020.12.21 View 12967