CES
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Mystery Solved with Math: Cytoplasmic Traffic Jam Disrupts Sleep-Wake Cycles
KAIST mathematicians and their collaborators at Florida State University have identified the principle of how aging and diseases like dementia and obesity cause sleep disorders. A combination of mathematical modelling and experiments demonstrated that the cytoplasmic congestion caused by aging, dementia, and/or obesity disrupts the circadian rhythms in the human body and leads to irregular sleep-wake cycles. This finding suggests new treatment strategies for addressing unstable sleep-wake cycles.
Human bodies adjust sleep schedules in accordance with the ‘circadian rhythms’, which are regulated by our time keeping system, the ‘circadian clock’. This clock tells our body when to rest by generating the 24-hour rhythms of a protein called PERIOD (PER) (See Figure 1).
The amount of the PER protein increases for half of the day and then decreases for the remaining half. The principle is that the PER protein accumulating in the cytoplasm for several hours enters the cell nucleus all at once, hindering the transcription of PER genes and thereby reducing the amount of PER.
However, it has remained a mystery how thousands of PER molecules can simultaneously enter into the nucleus in a complex cell environment where a variety of materials co-exist and can interfere with the motion of PER. This would be like finding a way for thousands of employees from all over New York City to enter an office building at the same time every day.
A group of researchers led by Professor Jae Kyoung Kim from the KAIST Department of Mathematical Sciences solved the mystery by developing a spatiotemporal and probabilistic model that describes the motion of PER molecules in a cell environment.
This study was conducted in collaboration with Professor Choogon Lee’s group from Florida State University, where the experiments were carried out, and the results were published in the Proceedings of the National Academy of Sciences (PNAS) last month.
The joint research team’s spatial stochastic model (See Figure 2) described the motion of PER molecules in cells and demonstrated that the PER molecule should be sufficiently condensed around the cell nucleus to be phosphorylated simultaneously and enter the nucleus together (See Figure 3 Left). Thanks to this phosphorylation synchronization switch, thousands of PER molecules can enter the nucleus at the same time every day and maintain stable circadian rhythms.
However, when aging and/or diseases including dementia and obesity cause the cytoplasm to become congested with increased cytoplasmic obstacles such as protein aggregates and fat vacuoles, it hinders the timely condensation of PER molecules around the cell nucleus (See Figure 3 Right). As a result, the phosphorylation synchronization switch does not work and PER proteins enter into the nucleus at irregular times, making the circadian rhythms and sleep-wake cycles unstable, the study revealed.
Professor Kim said, “As a mathematician, I am excited to help enable the advancement of new treatment strategies that can improve the lives of so many patients who suffer from irregular sleep-wake cycles. Taking these findings as an opportunity, I hope to see more active interchanges of ideas and collaboration between mathematical and biological sciences.”
This work was supported by the National Institutes of Health and the National Science Foundation in the US, and the International Human Frontiers Science Program Organization and the National Research Foundation of Korea.
Publication:
Beesley, S. and Kim, D. W, et al. (2020) Wake-sleep cycles are severely disrupted by diseases affecting cytoplasmic homeostasis. Proceedings of the National Academy of Sciences (PNAS), Vol. 117, No. 45, 28402-28411. Available online at https://doi.org/10.1073/pnas.2003524117
Profile:
Jae Kyoung Kim, Ph.D.
Associate Professor
jaekkim@kaist.ac.kr
http://mathsci.kaist.ac.kr/~jaekkim
@umichkim on Twitter
Department of Mathematical Sciences
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
Profile:
Choogon Lee, Ph.D.
Associate Professor
clee@neuro.fsu.edu
https://med.fsu.edu/biosci/lee-lab
Department of Biomedical Sciences
Florida State University
Florida, USA
(END)
2020.12.11 View 12661 -
A Comprehensive Review of Biosynthesis of Inorganic Nanomaterials Using Microorganisms and Bacteriophages
There are diverse methods for producing numerous inorganic nanomaterials involving many experimental variables. Among the numerous possible matches, finding the best pair for synthesizing in an environmentally friendly way has been a longstanding challenge for researchers and industries.
A KAIST bioprocess engineering research team led by Distinguished Professor Sang Yup Lee conducted a summary of 146 biosynthesized single and multi-element inorganic nanomaterials covering 55 elements in the periodic table synthesized using wild-type and genetically engineered microorganisms. Their research highlights the diverse applications of biogenic nanomaterials and gives strategies for improving the biosynthesis of nanomaterials in terms of their producibility, crystallinity, size, and shape.
The research team described a 10-step flow chart for developing the biosynthesis of inorganic nanomaterials using microorganisms and bacteriophages. The research was published at Nature Review Chemistry as a cover and hero paper on December 3.
“We suggest general strategies for microbial nanomaterial biosynthesis via a step-by-step flow chart and give our perspectives on the future of nanomaterial biosynthesis and applications. This flow chart will serve as a general guide for those wishing to prepare biosynthetic inorganic nanomaterials using microbial cells,” explained Dr.Yoojin Choi, a co-author of this research.
Most inorganic nanomaterials are produced using physical and chemical methods and biological synthesis has been gaining more and more attention. However, conventional synthesis processes have drawbacks in terms of high energy consumption and non-environmentally friendly processes. Meanwhile, microorganisms such as microalgae, yeasts, fungi, bacteria, and even viruses can be utilized as biofactories to produce single and multi-element inorganic nanomaterials under mild conditions.
After conducting a massive survey, the research team summed up that the development of genetically engineered microorganisms with increased inorganic-ion-binding affinity, inorganic-ion-reduction ability, and nanomaterial biosynthetic efficiency has enabled the synthesis of many inorganic nanomaterials.
Among the strategies, the team introduced their analysis of a Pourbaix diagram for controlling the size and morphology of a product. The research team said this Pourbaix diagram analysis can be widely employed for biosynthesizing new nanomaterials with industrial applications.Professor Sang Yup Lee added, “This research provides extensive information and perspectives on the biosynthesis of diverse inorganic nanomaterials using microorganisms and bacteriophages and their applications. We expect that biosynthetic inorganic nanomaterials will find more diverse and innovative applications across diverse fields of science and technology.”
Dr. Choi started this research in 2018 and her interview about completing this extensive research was featured in an article at Nature Career article on December 4.
-ProfileDistinguished Professor Sang Yup Lee leesy@kaist.ac.krMetabolic &Biomolecular Engineering National Research Laboratoryhttp://mbel.kaist.ac.krDepartment of Chemical and Biomolecular EngineeringKAIST
2020.12.07 View 13107 -
Drawing the Line to Answer Art’s Big Questions
- KAIST scientists show how statistical physics can reveal art trends across time and culture. -
Algorithms have shown that the compositional structure of Western landscape paintings changed “suspiciously” smoothly between 1500 and 2000 AD, potentially indicating a selection bias by art curators or in art historical literature, physicists from the Korea Advanced Institute of Science and Technology (KAIST) and colleagues report in the Proceedings of the National Academy of Sciences (PNAS).
KAIST statistical physicist Hawoong Jeong worked with statisticians, digital analysts and art historians in Korea, Estonia and the US to clarify whether computer algorithms could help resolve long-standing questions about design principles used in landscape paintings, such as the placement of the horizon and other primary features.
“A foundational question among art historians is whether artwork contains organizing principles that transcend culture and time and, if yes, how these principles evolved over time,” explains Jeong. “We developed an information-theoretic approach that can capture compositional proportion in landscape paintings and found that the preferred compositional proportion systematically evolved over time.”
Digital versions of almost 15,000 canonical landscape paintings from the Western renaissance in the 1500s to the more recent contemporary art period were run through a computer algorithm. The algorithm progressively divides artwork into horizontal and vertical lines depending on the amount of information in each subsequent partition. It allows scientists to evaluate how artists and various art styles compose landscape artwork, in terms of placement of a piece’s most important components, in addition to how high or low the landscape’s horizon is placed.
The scientists started by analysing the first two partitioning lines identified by the algorithm in the paintings and found they could be categorized into four groups: an initial horizontal line followed by a second horizontal line (H-H); an initial horizontal line followed by a second vertical line (H-V); a vertical followed by horizontal line (V-H); or a vertical followed by a vertical line (V-V) (see image 1 and 2). They then looked at the categorizations over time.
They found that before the mid-nineteenth century, H-V was the dominant composition type, followed by H-H, V-H, and V-V. The mid-nineteenth century then brought change, with the H-V composition style decreasing in popularity with a rise in the H-H composition style. The other two styles remained relatively stable.
The scientists also looked at how the horizon line, which separates sky from land, changed over time. In the 16th century, the dominant horizon line of the painting was above the middle of the canvas, but it gradually descended to the lower middle of the canvas by the 17th century, where it remained until the mid-nineteenth century. After that, the horizon line began gradually rising again.
Interestingly, the algorithm showed that these findings were similar across cultures and artistic periods, even through periods dominated by a diversity in art styles. This similarity may well be a function, then, of a bias in the dataset.
“In recent decades, art historians have prioritized the argument that there is great diversity in the evolution of artistic expression rather than offering a relatively smoother consensus story in Western art,” Jeong says. “This study serves as a reminder that the available large-scale datasets might be perpetuating severe biases.”
The scientists next aim to broaden their analyses to include more diverse artwork, as this particular dataset was ultimately Western and male biased. Future analyses should also consider diagonal compositions in paintings, they say.
This work was supported by the National Research Foundation (NRF) of Korea.
Publication:
Lee, B, et al. (2020) Dissecting landscape art history with information theory. Proceedings of the National Academy of Sciences (PNAS), Vol. 117, No. 43, 26580-26590. Available online at https://doi.org/10.1073/pnas.2011927117
Profile:
Hawoong Jeong, Ph.D.
Professor
hjeong@kaist.ac.kr
https://www.kaist.ac.kr
Department of Physics
Korea Advanced Institute of Science and Technology (KAIST)
Daejeon, Republic of Korea
(END)
2020.11.13 View 13383 -
Professor Won-Ki Cho Selected as the 2020 SUHF Young Investigator
Professor Won-Ki Cho from the Department of Biological Sciences was named one of three recipients of the 2020 Suh Kyung-Bae Science Foundation (SUHF) Young Investigator Award.
The SUHF is a non-profit organization established in 2016 and funded by a personal donation of 300 billion KRW in shares from Chairman and CEO Kyung-Bae Suh of the Amorepacific Group. The primary purpose of the foundation is to serve as a platform to nurture and provide comprehensive long-term support for creative and passionate young Korean scientists committed to pursuing research in the field of life sciences. The SUHF selects three to five scientists through an open recruiting process every year and grants each scientist a maximum of 2.5 billion KRW over a period of up to five years.
Since January this year, the foundation received 67 research proposals from scientists across the nation, especially from those who had less than five years of experience as professors, and selected the three recipients.
Professor Cho proposed research on how to observe the interactions between nuclear structures and constantly-changing chromatin monomers in four dimensions through ultra-high-resolution imaging of single living cells. This proposal was recognized as one that could help us better understand the process of transcription regulation, which remains a long-standing question in biology.
The other awards were given to Professor Soung-hun Roh of Seoul National University and Professor Joo-Hyeon Lee of the University of Cambridge.
With these three new awardees, a total of 17 scientists have been named SUHF Young Investigators to date, and the funding to support these scientists now totals 42.5 billion KRW.
Professor Inkyung Jung and Professor Ki-Jun Yoon from the Department of Biological Sciences, and Professor Young Seok Ju and Professor Jeong Ho Lee from the Graduate School of Medical Science and Engineering are the four previous winners from KAIST in the years 2017 through 2019.
(END)
2020.10.15 View 15927 -
Before Eyes Open, They Get Ready to See
- Spontaneous retinal waves can generate long-range horizontal connectivity in visual cortex. -
A KAIST research team’s computational simulations demonstrated that the waves of spontaneous neural activity in the retinas of still-closed eyes in mammals develop long-range horizontal connections in the visual cortex during early developmental stages.
This new finding featured in the August 19 edition of Journal of Neuroscience as a cover article has resolved a long-standing puzzle for understanding visual neuroscience regarding the early organization of functional architectures in the mammalian visual cortex before eye-opening, especially the long-range horizontal connectivity known as “feature-specific” circuitry.
To prepare the animal to see when its eyes open, neural circuits in the brain’s visual system must begin developing earlier. However, the proper development of many brain regions involved in vision generally requires sensory input through the eyes.
In the primary visual cortex of the higher mammalian taxa, cortical neurons of similar functional tuning to a visual feature are linked together by long-range horizontal circuits that play a crucial role in visual information processing.
Surprisingly, these long-range horizontal connections in the primary visual cortex of higher mammals emerge before the onset of sensory experience, and the mechanism underlying this phenomenon has remained elusive.
To investigate this mechanism, a group of researchers led by Professor Se-Bum Paik from the Department of Bio and Brain Engineering at KAIST implemented computational simulations of early visual pathways using data obtained from the retinal circuits in young animals before eye-opening, including cats, monkeys, and mice.
From these simulations, the researchers found that spontaneous waves propagating in ON and OFF retinal mosaics can initialize the wiring of long-range horizontal connections by selectively co-activating cortical neurons of similar functional tuning, whereas equivalent random activities cannot induce such organizations.
The simulations also showed that emerged long-range horizontal connections can induce the patterned cortical activities, matching the topography of underlying functional maps even in salt-and-pepper type organizations observed in rodents. This result implies that the model developed by Professor Paik and his group can provide a universal principle for the developmental mechanism of long-range horizontal connections in both higher mammals as well as rodents.
Professor Paik said, “Our model provides a deeper understanding of how the functional architectures in the visual cortex can originate from the spatial organization of the periphery, without sensory experience during early developmental periods.”
He continued, “We believe that our findings will be of great interest to scientists working in a wide range of fields such as neuroscience, vision science, and developmental biology.”
This work was supported by the National Research Foundation of Korea (NRF). Undergraduate student Jinwoo Kim participated in this research project and presented the findings as the lead author as part of the Undergraduate Research Participation (URP) Program at KAIST.
Figures and image credit: Professor Se-Bum Paik, KAIST
Image usage restrictions: News organizations may use or redistribute these figures and image, with proper attribution, as part of news coverage of this paper only.
Publication:
Jinwoo Kim, Min Song, and Se-Bum Paik. (2020). Spontaneous retinal waves generate long-range horizontal connectivity in visual cortex. Journal of Neuroscience, Available online athttps://www.jneurosci.org/content/early/2020/07/17/JNEUROSCI.0649-20.2020
Profile: Se-Bum Paik
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: Jinwoo Kim
Undergraduate Student
bugkjw@kaist.ac.kr
Department of Bio and Brain Engineering, KAIST
Profile: Min Song
Ph.D. Candidate
night@kaist.ac.kr
Program of Brain and Cognitive Engineering, KAIST
(END)
2020.08.25 View 15514 -
Tinkering with Roundworm Proteins Offers Hope for Anti-aging Drugs
- The somatic nuclear protein kinase VRK-1 increases the worm’s lifespan through AMPK activation, and this mechanism can be applied to promoting human longevity, the study reveals. -
KAIST researchers have been able to dial up and down creatures’ lifespans by altering the activity of proteins found in roundworm cells that tell them to convert sugar into energy when their cellular energy is running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings were published on July 1 in Science Advances.
The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long nematode commonly used in lab testing, enjoyed a boost in its lifespan when researchers tinkered with a couple of proteins involved in monitoring the energy use by its cells.
The proteins VRK-1 and AMPK work in tandem in roundworm cells, with the former telling the latter to get to work by sticking a phosphate molecule, composed of one phosphorus and four oxygen atoms, on it. In turn, AMPK’s role is to monitor energy levels in cells, when cellular energy is running low. In essence, VRK-1 regulates AMPK, and AMPK regulates the cellular energy status.
Using a range of different biological research tools, including introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at KAIST were able to dial up and down the activity of the gene that tells cells to produce the VRK-1 protein. This gene has remained pretty much unchanged throughout evolution. Most complex organisms have this same gene, including humans.
Lead author of the study Sangsoon Park and his colleagues confirmed that the overexpression, or increased production, of the VRK-1 protein boosted the lifespan of the C. elegans, which normally lives just two to three weeks, and the inhibition of VRK-1 production reduced its lifespan.
The research team found that the activity of the VRK-1-to-AMPK cellular-energy monitoring process is increased in low cellular energy status by reduced mitochondrial respiration, the set of metabolic chemical reactions that make use of the oxygen the worm breathes to convert macronutrients from food into the energy “currency” that cells spend to do everything they need to do.
It is already known that mitochondria, the energy-producing engine rooms in cells, play a crucial role in aging, and declines in the functioning of mitochondria are associated with age-related diseases. At the same time, the mild inhibition of mitochondrial respiration has been shown to promote longevity in a range of species, including flies and mammals.
When the research team performed similar tinkering with cultured human cells, they found they could also replicate this ramping up and down of the VRK-1-to-AMPK process that occurs in roundworms.
“This raises the intriguing possibility that VRK-1 also functions as a factor in governing human longevity, and so perhaps we can start developing longevity-promoting drugs that alter the activity of VRK-1,” explained Professor Lee.
At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of the mitochondria.
But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried out to better understand how VRK-1 works to activate AMPK, as well as figure out the precise mechanics of how AMPK controls cellular energy.
This work was supported by the National Research Foundation (NRF), and the Ministry of Science and ICT (MSIT) of Korea.
Image credit: Seung-Jae V. LEE, 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:
Park, S., et al. (2020) ‘VRK-1 extends life span by activation of AMPK via phosphorylation’. Science Advances, Volume 6. No. 27, eaaw7824. Available online at https://doi.org/10.1126/sciadv.aaw7824
Profile: Seung-Jae V. Lee, Ph.D.
Professor
seungjaevlee@kaist.ac.kr
https://sites.google.com/view/mgakaist
Molecular Genetics of Aging Laboratory
Department of Biological Sciences
Korea Advanced Institute of Science and Technology (KAIST)
https://www.kaist.ac.krDaejeon 34141, Korea
(END)
2020.07.31 View 13841 -
Hydrogel-Based Flexible Brain-Machine Interface
The interface is easy to insert into the body when dry, but behaves ‘stealthily’ inside the brain when wet
Professor Seongjun Park’s research team and collaborators revealed a newly developed hydrogel-based flexible brain-machine interface. To study the structure of the brain or to identify and treat neurological diseases, it is crucial to develop an interface that can stimulate the brain and detect its signals in real time. However, existing neural interfaces are mechanically and chemically different from real brain tissue. This causes foreign body response and forms an insulating layer (glial scar) around the interface, which shortens its lifespan.
To solve this problem, the research team developed a ‘brain-mimicking interface’ by inserting a custom-made multifunctional fiber bundle into the hydrogel body. The device is composed not only of an optical fiber that controls specific nerve cells with light in order to perform optogenetic procedures, but it also has an electrode bundle to read brain signals and a microfluidic channel to deliver drugs to the brain.
The interface is easy to insert into the body when dry, as hydrogels become solid. But once in the body, the hydrogel will quickly absorb body fluids and resemble the properties of its surrounding tissues, thereby minimizing foreign body response.
The research team applied the device on animal models, and showed that it was possible to detect neural signals for up to six months, which is far beyond what had been previously recorded. It was also possible to conduct long-term optogenetic and behavioral experiments on freely moving mice with a significant reduction in foreign body responses such as glial and immunological activation compared to existing devices.
“This research is significant in that it was the first to utilize a hydrogel as part of a multifunctional neural interface probe, which increased its lifespan dramatically,” said Professor Park. “With our discovery, we look forward to advancements in research on neurological disorders like Alzheimer’s or Parkinson’s disease that require long-term observation.”
The research was published in Nature Communications on June 8, 2021. (Title: Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity) The study was conducted jointly with an MIT research team composed of Professor Polina Anikeeva, Professor Xuanhe Zhao, and Dr. Hyunwoo Yook.
This research was supported by the National Research Foundation (NRF) grant for emerging research, Korea Medical Device Development Fund, KK-JRC Smart Project, KAIST Global Initiative Program, and Post-AI Project.
-Publication
Park, S., Yuk, H., Zhao, R. et al. Adaptive and multifunctional hydrogel hybrid probes for long-term sensing and modulation of neural activity. Nat Commun 12, 3435 (2021). https://doi.org/10.1038/s41467-021-23802-9
-Profile
Professor Seongjun Park
Bio and Neural Interfaces Laboratory
Department of Bio and Brain Engineering
KAIST
2020.07.13 View 9490 -
X-ray Scattering Shines Light on Protein Folding
- Multiple forms of a non-functional, unfolded protein follow different pathways and timelines to reach its folded, functional state, a study reveals. -
KAIST researchers have used an X-ray method to track how proteins fold, which could improve computer simulations of this process, with implications for understanding diseases and improving drug discovery. Their findings were reported in the Proceedings of the National Academy of Sciences of the United States of America (PNAS) on June 30.
When proteins are translated from their DNA codes, they quickly transform from a non-functional, unfolded state into their folded, functional state. Problems in folding can lead to diseases like Alzheimer’s and Parkinson’s.
“Protein folding is one of the most important biological processes, as it forms the functioning 3D protein structure,” explained the physical chemist Hyotcherl Ihee of the Department of Chemistry at KAIST. Dr. Tae Wu Kim, the lead author of this research from Ihee’s group, added, “Understanding the mechanisms of protein folding is important, and could pave the way for disease study and drug development.”
Ihee’s team developed an approach using an X-ray scattering technique to uncover how the protein cytochrome c folds from its initial unfolded state. This protein is composed of a chain of 104 amino acids with an iron-containing heme molecule. It is often used for protein folding studies.
The researchers placed the protein in a solution and shined ultraviolet light on it. This process provides electrons to cytochrome c, reducing the iron within it from the ferric to the ferrous form, which initiates folding. As this was happening, the researchers beamed X-rays at very short intervals onto the sample. The X-rays scattered off all the atomic pairs in the sample and a detector continuously recorded the X-ray scattering patterns. The X-ray scattering patterns provided direct information regarding the 3D protein structure and the changes made in these patterns over time showed real-time motion of the protein during the folding process.
The team found cytochrome c proteins initially exist in a wide variety of unfolded states. Once the folding process is triggered, they stop by a group of intermediates within 31.6 microseconds, and then those intermediates follow different pathways with different folding times to reach an energetically stable folded state.
“We don’t know if this diversity in folding paths can be generalized to other proteins,” Ihee confessed. He continued, “However, we believe that our approach can be used to study other protein folding systems.”
Ihee hopes this approach can improve the accuracy of models that simulate protein interactions by including information on their unstructured states. These simulations are important as they can help identify barriers to proper folding and predict a protein’s folded state given its amino acid sequence. Ultimately, the models could help clarify how some diseases develop and how drugs interact with various protein structures.
Ihee’s group collaborated with Professor Young Min Rhee at the KAIST Department of Chemistry, and this work was supported by the National Research Foundation of Korea (NRF) and the Institute for Basic Science (IBS).
Figure. The scientists found that non-functional unfolded forms of the protein cytochrome c follow different pathways and timelines to reach a stable functional folded state.
Publications:
Kim, T. W., et al. (2020) ‘Protein folding from heterogeneous unfolded state revealed by time-resolved X-ray solution scattering’. PNAS. Volume 117. Issue 26. Page 14996-15005. Available online at https://doi.org/10.1073/pnas.1913442117
Profile: Hyotcherl Ihee, Ph.D.
Professor
hyotcherl.ihee@kaist.ac.kr
http://time.kaist.ac.kr/
Ihee Laboratory
Department of Chemistry
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Young Min Rhee, Ph.D.
Professor
ymrhee@kaist.ac.kr
http://singlet.kaist.ac.kr
Rhee Research Group
Department of Chemistry
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
(END)
2020.07.09 View 17720 -
Simple Molecular Reagents to Treat Alzheimer’s Disease
- Researchers report minimalistic principles for designing small molecules with multiple reactivities against dementia. -
Sometimes the most complex problems actually have very simple solutions. A group of South Korean researchers reported an efficient and effective redox-based strategy for incorporating multiple functions into simple molecular reagents against neurodegenerative disorders. The team developed redox-active aromatic molecular reagents with a simple structural composition that can simultaneously target and modulate various pathogenic factors in complex neurodegenerative disorders such as Alzheimer’s disease.
Alzheimer’s disease is one of the most prevalent neurodegenerative disorders, affecting one in ten people over the age of 65. Early-onset dementia also increasingly affects younger people.
A number of pathogenic elements such as reactive oxygen species, amyloid-beta, and metal ions have been suggested as potential causes of Alzheimer’s disease. Each element itself can lead to Alzheimer’s disease, but interactions between them may also aggravate the patient’s condition or interfere with the appropriate clinical care.
For example, when interacting with amyloid-beta, metal ions foster the aggregation and accumulation of amyloid-beta peptides that can induce oxidative stress and toxicity in the brain and lead to neurodegeneration.
Because these pathogenic factors of Alzheimer’s disease are intertwined, developing therapeutic agents that are capable of simultaneously regulating metal ion dyshomeostasis, amyloid-beta agglutination, and oxidative stress responses remains a key to halting the progression of the disease.
A research team led by Professor Mi Hee Lim from the Department of Chemistry at KAIST demonstrated the feasibility of structure-mechanism-based molecular design for controlling a molecule’s chemical reactivity toward the various pathological factors of Alzheimer’s disease by tuning the redox properties of the molecule.
This study, featured as the ‘ACS Editors’ Choice’ in the May 6th issue of the Journal of the American Chemical Society (JACS), was conducted in conjunction with KAIST Professor Mu-Hyun Baik’s group and Professor Joo-Young Lee’s group at the Asan Medical Center.
Professor Lim and her collaborators rationally designed and generated 10 compact aromatic molecules presenting a range of redox potentials by adjusting the electronic distribution of the phenyl, phenylene, or pyridyl moiety to impart redox-dependent reactivities against the multiple pathogenic factors in Alzheimer’s disease.
During the team’s biochemical and biophysical studies, these designed molecular reagents displayed redox-dependent reactivities against numerous desirable targets that are associated with Alzheimer’s disease such as free radicals, metal-free amyloid-beta, and metal-bound amyloid-beta.
Further mechanistic results revealed that the redox properties of these designed molecular reagents were essential for their function. The team demonstrated that these reagents engaged in oxidative reactions with metal-free and metal-bound amyloid-beta and led to chemical modifications. The products of such oxidative transformations were observed to form covalent adducts with amyloid-beta and alter its aggregation.
Moreover, the administration of the most promising candidate molecule significantly attenuated the amyloid pathology in the brains of Alzheimer’s disease transgenic mice and improved their cognitive defects.
Professor Lim said, “This strategy is straightforward, time-saving, and cost-effective, and its effect is significant. We are excited to help enable the advancement of new therapeutic agents for neurodegenerative disorders, which can improve the lives of so many patients.”
This work was supported by the National Research Foundation (NRF) of Korea, the Institute for Basic Science (IBS), and the Asan Institute for Life Sciences.
Image credit: Professor Mi Hee Lim, KAIST
Image usage restrictions: News organizations may use or redistribute this image, with proper attribution, as part of the news coverage of this paper only.
Publication:
Kim, M. et al. (2020) ‘Minimalistic Principles for Designing Small Molecules with Multiple Reactivities against Pathological Factors in Dementia.’ Journal of the American Chemical Society (JACS), Volume 142, Issue 18, pp.8183-8193. Available online at https://doi.org/10.1021/jacs.9b13100
Profile:
Mi Hee Lim
Professor
miheelim@kaist.ac.kr
http://sites.google.com/site/miheelimlab
Lim Laboratory
Department of Chemistry
KAIST
Profile:
Mu-Hyun Baik
Professor
mbaik2805@kaist.ac.kr
https://baik-laboratory.com/
Baik Laboratory
Department of Chemistry
KAIST
Profile:
Joo-Yong Lee
Professor
jlee@amc.seoul.kr
Asan Institute for Life Sciences
Asan Medical Center
(END)
2020.05.11 View 18562 -
A Study Finds Neuropeptide Somatostatin Enhances Visual Processing
Researchers have confirmed that neuropeptide somatostatin can improve cognitive function in the brain. A research group of Professor Seung-Hee Lee from the Department of Biological Sciences at KAIST found that the application of neuropeptide somatostatin improves visual processing and cognitive behaviors by reducing excitatory inputs to parvalbumin-positive interneurons in the cortex.
This study, reported at Science Advances on April 22nd (EST), sheds a new light on the therapeutics of neurodegenerative diseases. According to a recent study in Korea, one in ten seniors over 65 is experiencing dementia-related symptoms in their daily lives such like memory loss, cognitive decline, and motion function disorders. Professor Lee believes that somatostatin treatment can be directly applied to the recovery of cognitive functions in Alzheimer’s disease patients.
Professor Lee started this study noting the fact that the level of somatostatin expression was dramatically decreased in the cerebral cortex and cerebrospinal fluid of Alzheimer’s disease patients
Somatostatin-expressing neurons in the cortex are known to exert the dendritic inhibition of pyramidal neurons via GABAergic transmission. Previous studies focused on their inhibitory effects on cortical circuits, but somatostatin-expressing neurons can co-release somatostatin upon activation. Despite the abundant expression of somatostatin and its receptors in the cerebral cortex, it was not known if somatostatin could modulate cognitive processing in the cortex.
The research team demonstrated that the somatostatin treatment into the cerebral cortex could enhance visual processing and cognitive behaviors in mice. The research team combined behaviors, in vivo and in vitro electrophysiology, and electron microscopy techniques to reveal how the activation of somatostatin receptors in vivo enhanced the ability of visual recognition in animals. Interestingly, somatostatin release can reduce excitatory synaptic transmission to another subtype of GABAergic interneurons, parvalbumin (PV)-expressing neurons.
As somatostatin is a stable and safe neuropeptide expressed naturally in the mammalian brain, it was safe to be injected into the cortex and cerebrospinal fluid, showing a potential application to drug development for curing cognitive disorders in humans.
Professor Lee said, “Our research confirmed the key role of the neuropeptide SST in modulating cortical function and enhancing cognitive ability in the mammalian brain. I hope new drugs can be developed based on the function of somatostatin to treat cognitive disabilities in many patients suffering from neurological disorders.”
This study was supported by the National Research Foundation of Korea.
Publication:
Song, Y. H et al. (2020) ‘Somatostatin enhances visual processing and perception by suppressing excitatory inputs to parvalbumin-positive interneurons in V1’, Science Advances, 6(17). Available online at https://doi.org/10.1126/sciadv.aaz0517
Profile:
Seung-Hee Lee
Associate Professor
shlee1@kaist.ac.kr
https://sites.google.com/site/leelab2013/
Sensory Processing Lab (SPL)
Department of Biological Sciences (BIO)
Korea Advanced Institute of Science and Technology (KAIST)
Profile:
You-Hyang Song
Researcher (Ph.D.)
dbgidtm17@kaist.ac.kr
SPL, KAIST BIO
Profile:
Yang-Sun Hwang
Researcher (M.S.)
hys940129@kaist.ac.kr
SPL, KAIST BIO
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2020.04.23 View 15221 -
14-Day Drawing Challenge Helps Maintain a Sense of Connection Amid Prolonged Social Distancing
- “You need space, but you also need connections.” -
Schools and workplaces have closed and people are staying at home around the globe. Governments across the world have urged their people to keep a distance from others as a measure to slow the spread of the pandemic.
With the Korean government’s decision to extend the intensive social distancing campaign until at least April 19, people in Korea are advised to avoid nonessential trips, public facilities, and social gatherings for another two weeks or so.
This unprecedented prolonged social distancing drive leads people to feel fatigue and frustration. Such emotional stress is worse for those who live alone in a foreign country.
The International Scholar and Student Services (ISSS) Team at KAIST has been working around the clock to build a dedicated COVID-19 Mental Health Support Service to support the university’s international community on campus and abroad and help get them connected online.
As the COVID-19 situation lingers, there has been a growing demand for mental health support from many KAIST international members including 299 students who have been staying in Korea on their own and away from their families, as well as from those who could not return to campus from their overseas homes.
In response to this, the KAIST ISSS Team has been offering some special online events and programs that can help the KAIST international community stay feeling connected whereever they are, while still keeping a safe distance from each other.
For instance, the team is running an art-therapy program called ‘The 14-day Drawing Challenge’ March 30 through April 12. This program is online and individual-based, so it does not require any physical contact between participants.
Each participant is asked to draw a picture at home using the daily topics previously set by the ISSS Team over 14 days. The topics include (Day 1) self-portrait, (Day 2) spring flowers, (Day 3) if you could become anything…, (Day 4) funniest memory you have, (Day 5) animals at KAIST, (Day 6) something you love, (Day 7) country or city you want to visit, (Day 8) what’s for dinner? (Day 9) person you miss, (Day 10) your favorite place at KAIST, (Day 11) your feeling today, (Day 12) things in your favorite color, (Day 13) song lyrics, and (Day 14) your future self in 10 years.
Once all 14 pieces have been completed, submissions can be made online by sending an e-mail to the ISSS Team after scanning or taking a photo of each drawing. Selected submissions will be awarded small prizes for participation and shared through the university’s official website and SNS channels.
“All the participants need is paper, coloring tools, and their creativity and imagination. They don’t have to be a great artist to join this challenge. There is no right or wrong or good or bad. They just need to have fun drawing every day for two weeks, ease their coronavirus anxiety, and remain emotionally stable just like they did back in the normal days,” said Su-yeon Ahn, the manager of the KAIST ISSS Team. She added, “In times like these, you need space, but you also need connections. Our team wants our international students, professors, and researchers to build strong connections with each other, even online.”
Katherine Michelle Pena Santana, an M.S. candidate from the Department of Industrial and Systems Engineering who is taking part in ‘The 14-day Drawing Challenge,’ looked back and said, “Lately with the new coronavirus spreading around Korea and the entire world, I was feeling very anxious. I didn't get out of my room and lived by just looking at the same walls and creating some kind of a psychological burden on myself.”
Santana added that these kinds of activities could give many foreign members of KAIST an opportunity to not only relieve fear and stress, but also share each other’s experiences dealing with this pandemic. She explained that this is why she decided to participate in this challenge.
An undergraduate student from the Department of Physics, Ada Carpenter, appreciated the KAIST ISSS Team’s efforts to provide a variety of special online mental health support services to help the university’s international community socialize, while strictly following the government’s guidelines for social distancing. She expressed excitement about participating and said, “I’m so looking forward to the challenge of things that I wouldn’t normally draw.”
< Short Self-interview Video Clip Filmed by Ada Carpenter >
The COVID-19 Mental Health Support Service by the KAIST ISSS Team will be continually updated with new information and enhanced with other tools and support over the coming weeks and months. Some of the upcoming events and programs include ‘The Online Guitar Lessons’, ‘The Growing Houseplants Challenge’, and ‘The Any Song Challenge*’.
* The song titled “Any Song” by Korean rapper Zico has been gaining attention on social media thanks to many celebrities taking on the ‘Any Song Challenge’, performing a short dance to the chorus of the song and sharing it on social media.
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2020.04.08 View 12259 -
Wearable Strain Sensor Using Light Transmittance Helps Measure Physical Signals Better
KAIST researchers have developed a novel wearable strain sensor based on the modulation of optical transmittance of a carbon nanotube (CNT)-embedded elastomer. The sensor is capable of sensitive, stable, and continuous measurement of physical signals. This technology, featured in the March 4th issue of ACS Applied Materials & Interfaces as a front cover article, shows great potential for the detection of subtle human motions and the real-time monitoring of body postures for healthcare applications.
A wearable strain sensor must have high sensitivity, flexibility, and stretchability, as well as low cost. Those used especially for health monitoring should also be tied to long-term solid performance, and be environmentally stable. Various stretchable strain sensors based on piezo-resistive and capacitive principles have been developed to meet all these requirements.
Conventional piezo-resistive strain sensors using functional nanomaterials, including CNTs as the most common example, have shown high sensitivity and great sensing performance. However, they suffer from poor long-term stability and linearity, as well as considerable signal hysteresis. As an alternative, piezo-capacitive strain sensors with better stability, lower hysteresis, and higher stretchability have been suggested. But due to the fact that piezo-capacitive strain sensors exhibit limited sensitivity and strong electromagnetic interference caused by the conductive objects in the surrounding environment, these conventional stretchable strain sensors are still facing limitations that are yet to be resolved.
A KAIST research team led by Professor Inkyu Park from the Department of Mechanical Engineering suggested that an optical-type stretchable strain sensor can be a good alternative to resolve the limitations of conventional piezo-resistive and piezo-capacitive strain sensors, because they have high stability and are less affected by environmental disturbances. The team then introduced an optical wearable strain sensor based on the light transmittance changes of a CNT-embedded elastomer, which further addresses the low sensitivity problem of conventional optical stretchable strain sensors.
In order to achieve a large dynamic range for the sensor, Professor Park and his researchers chose Ecoflex as an elastomeric substrate with good mechanical durability, flexibility, and attachability on human skin, and the new optical wearable strain sensor developed by the research group actually shows a wide dynamic range of 0 to 400%.
In addition, the researchers propagated the microcracks under tensile strain within the film of multi-walled CNTs embedded in the Ecoflex substrate, changing the optical transmittance of the film. By doing so, it was possible for them to develop a wearable strain sensor having a sensitivity 10 times higher than conventional optical stretchable strain sensors.
The proposed sensor has also passed the durability test with excellent results. The sensor’s response after 13,000 sets of cyclic loading was stable without any noticeable drift. This suggests that the sensor response can be used without degradation, even if the sensor is repeatedly used for a long time and in various environmental conditions.
Using the developed sensor, the research team could measure the finger bending motion and used it for robot control. They also developed a three-axes sensor array for body posture monitoring. The sensor was able to monitor human motions with small strains such as a pulse near the carotid artery and muscle movement around the mouth during pronunciation.
Professor Park said, “In this study, our group developed a new wearable strain sensor platform that overcomes many limitations of previously developed resistive, capacitive, and optical-type stretchable strain sensors. Our sensor could be widely used in a variety of fields including soft robotics, wearable electronics, electronic skin, healthcare, and even entertainment.”
This work was supported by the National Research Foundation (NRF) of Korea.
Publication:
Jimin Gu, Donguk Kwon, Junseong Ahn, and Inkyu Park. (2020) “Wearable Strain sensors Using Light Transmittance Change of Carbon Nanotube-Embedded Elastomers with Microcracks” ACS Applied Materials & Interfaces. Volume 12. Issue 9. Available online at https://doi.org/10.1021/acsami.9b18069
Profile:
Inkyu Park
Professor
inkyu@kaist.ac.kr
http://mintlab1.kaist.ac.kr
Micro/Nano Transducers Laboratory (MINT Lab)
Department of Mechanical Engineering (ME)Korea Advanced Institute of Science and Technology (KAIST)
Profile:
Jimin Gu
Ph.D. Candidate
mint9411@kaist.ac.kr
http://mintlab1.kaist.ac.kr
MINT Lab
KAIST ME
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2020.03.20 View 22775