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New Insights into How the Human Brain Solves Complex Decision-Making Problems
A new study on meta reinforcement learning algorithms helps us understand how the human brain learns to adapt to complexity and uncertainty when learning and making decisions. A research team, led by Professor Sang Wan Lee at KAIST jointly with John O’Doherty at Caltech, succeeded in discovering both a computational and neural mechanism for human meta reinforcement learning, opening up the possibility of porting key elements of human intelligence into artificial intelligence algorithms. This study provides a glimpse into how it might ultimately use computational models to reverse engineer human reinforcement learning.
This work was published on Dec 16, 2019 in the journal Nature Communications. The title of the paper is “Task complexity interacts with state-space uncertainty in the arbitration between model-based and model-free learning.”
Human reinforcement learning is an inherently complex and dynamic process, involving goal setting, strategy choice, action selection, strategy modification, cognitive resource allocation etc. This a very challenging problem for humans to solve owing to the rapidly changing and multifaced environment in which humans have to operate. To make matters worse, humans often need to often rapidly make important decisions even before getting the opportunity to collect a lot of information, unlike the case when using deep learning methods to model learning and decision-making in artificial intelligence applications.
In order to solve this problem, the research team used a technique called 'reinforcement learning theory-based experiment design' to optimize the three variables of the two-stage Markov decision task - goal, task complexity, and task uncertainty. This experimental design technique allowed the team not only to control confounding factors, but also to create a situation similar to that which occurs in actual human problem solving.
Secondly, the team used a technique called ‘model-based neuroimaging analysis.’ Based on the acquired behavior and fMRI data, more than 100 different types of meta reinforcement learning algorithms were pitted against each other to find a computational model that can explain both behavioral and neural data. Thirdly, for the sake of a more rigorous verification, the team applied an analytical method called ‘parameter recovery analysis,’ which involves high-precision behavioral profiling of both human subjects and computational models.
In this way, the team was able to accurately identify a computational model of meta reinforcement learning, ensuring not only that the model’s apparent behavior is similar to that of humans, but also that the model solves the problem in the same way as humans do.
The team found that people tended to increase planning-based reinforcement learning (called model-based control), in response to increasing task complexity. However, they resorted to a simpler, more resource efficient strategy called model-free control, when both uncertainty and task complexity were high. This suggests that both the task uncertainty and the task complexity interact during the meta control of reinforcement learning. Computational fMRI analyses revealed that task complexity interacts with neural representations of the reliability of the learning strategies in the inferior prefrontal cortex.
These findings significantly advance understanding of the nature of the computations being implemented in the inferior prefrontal cortex during meta reinforcement learning as well as providing insight into the more general question of how the brain resolves uncertainty and complexity in a dynamically changing environment. Identifying the key computational variables that drive prefrontal meta reinforcement learning, can also inform understanding of how this process might be vulnerable to break down in certain psychiatric disorders such as depression and OCD. Furthermore, gaining a computational understanding of how this process can sometimes lead to increased model-free control, can provide insights into how under some situations task performance might break down under conditions of high cognitive load.
Professor Lee said, “This study will be of enormous interest to researchers in both the artificial intelligence and human/computer interaction fields since this holds significant potential for applying core insights gleaned into how human intelligence works with AI algorithms.”
This work was funded by the National Institute on Drug Abuse, the National Research Foundation of Korea, the Ministry of Science and ICT, Samsung Research Funding Center of Samsung Electronics.
Figure 1 (modified from the figures of the original paper doi:10.1038/s41467-019-13632-1). Computations implemented in the inferior prefrontal cortex during meta reinforcement learning. (A) Computational model of human prefrontal meta reinforcement learning (left) and the brain areas whose neural activity patterns are explained by the latent variables of the model. (B) Examples of behavioral profiles. Shown on the left is choice bias for different goal types and on the right is choice optimality for task complexity and uncertainty. (C) Parameter recoverability analysis. Compared are the effect of task uncertainty (left) and task complexity (right) on choice optimality.
-Profile
Professor Sang Wan Lee
sangwan@kaist.ac.kr
Department of Bio and Brain Engineering
Director, KAIST Center for Neuroscience-inspired AI
KAIST Institute for Artificial Intelligence (http://aibrain.kaist.ac.kr)
KAIST Institute for Health, Science, and Technology
KAIST (https://www.kaist.ac.kr)
2020.01.31 View 6070 -
KAIST Vaccine for Tick-Borne Disease ‘SFTS’ Protects Against Lethal Infection
A KAIST research team reported the development of a DNA vaccine for Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) which completely protects against lethal infection in ferrets. The team confirmed that ferrets immunized with DNA vaccines encoding all SFTSV proteins showed 100% survival rate without detectable viremia and did not develop any clinical symptoms. This study was published in Nature Communications on August 23.
Severe Fever with Thrombocytopenia Syndrome (SFTS) is a newly emerging tick-borne infectious disease. The disease causes fever, severe thrombocytopenia, leukocytopenia as well as vomiting and diarrhea. Severe cases end up with organ system failure often accompanied by hemorrhages, and its mortality rate stands at 10–20%.
The viral disease has been endemic to East Asia but the spread of the tick vector to North America increases the likelihood of potential outbreak beyond the Far East Asia. The World Health Organization (WHO) has also put SFTSV into the priority pathogen requiring urgent attention category. Currently, no vaccine has been available to prevent SFTS.
The research team led by Professor Su-Hyung Park noted that DNA vaccines induce broader immunity to multiple antigens than traditional ones. Moreover, DNA vaccines stimulate both T cell and antibody immunity, which make them suitable for vaccine development.
They constructed DNA vaccines that encode full-length Gn, Gc, N, NS, and RNA polymerase genes based on common sequences of 31 SFTSV strains isolated from patients. Their vaccine candidates induced both neutralizing antibody response and multifunctional SFTSV-specific T cell response in mice and ferrets.
To investigate the vaccine’s efficacy in vivo, the research team applied a recently developed ferret model that recapitulates fatal clinical symptoms in SFTSV infection in humans. Vaccinated ferrets were completely protected from lethal SFTSV challenge without SFTSV detection in their blood, whereas all control ferrets died within 10 days’ post-infection.
The KAIST team found that anti-envelope antibodies play an important role in protective immunity, suggesting that envelope glycoproteins of SFTSV may be the most effective antigens for inducing protective immunity. Moreover, the study revealed that T cell responses specific to non-envelope proteins of SFTSV also can contribute to protection against SFTSV infection.
Professor Park said, “This is the first study demonstrating complete protection against lethal SFTSV challenge using an immunocompetent, middle-sized animal model with clinical manifestations of SFTSV infection. We believe this study provides valuable insights into designing preventive vaccines for SFTSV.”
2020.01.31 View 5387 -
Transformative Electronics Systems to Broaden Wearable Applications
Imagine a handheld electronic gadget that can soften and deform when attached to our skin. This will be the future of electronics we all dreamed of. A research team at KAIST says their new platform called 'Transformative Electronics Systems' will open a new class of electronics, allowing reconfigurable electronic interfaces to be optimized for a variety of applications.
A team working under Professor Jae-Woong Jeong from the School of Electrical Engineering at KAIST has invented a multifunctional electronic platform that can mechanically transform its shape, flexibility, and stretchability. This platform, which was reported in Science Advances, allows users to seamlessly and precisely tune its stiffness and shape.
"This new class of electronics will not only offer robust, convenient interfaces for use in both tabletop or handheld setups, but also allow seamless integration with the skin when applied onto our bodies," said Professor Jeong.
The transformative electronics consist of a special gallium metal structure, hermetically encapsulated and sealed within a soft silicone material, combined with electronics that are designed to be flexible and stretchable. The mechanical transformation of the electronic systems is specifically triggered by temperature change events controlled by the user.
"Gallium is an interesting key material. It is biocompatible, has high rigidity in solid form, and melts at a temperature comparable to the skin's temperature," said lead author Sang-Hyuk Byun, a researcher at KAIST.
Once the transformative electronic platform comes in contact with a human body, the gallium metal encapsulated inside the silicone changes to a liquid state and softens the whole electronic structure, making it stretchable, flexible, and wearable. The gallium metal then solidifies again once the structure is peeled off the skin, making the electronic circuits stiff and stable. When flexible electronic circuits were integrated onto these transformative platforms, it empowered them with the ability to become either flexible and stretchable or rigid.
"This technology could not have been achieved without interdisciplinary efforts," said co-lead author Joo Yong Sim, who is a researcher with ETRI. "We worked together with electrical, mechanical, and biomedical engineers, as well as material scientists and neuroscientists to make this breakthrough."
This universal electronics platform allowed researchers to demonstrate applications that were highly adaptable and customizable, such as a multi-purpose personal electronics with variable stiffness and stretchability, a pressure sensor with tuneable bandwidth and sensitivity, and a neural probe that softens upon implantation into brain tissue.
Applicable for both traditional and emerging electronics technologies, this breakthrough can potentially reshape the consumer electronics industry, especially in the biomedical and robotic domains. The researchers believe that with further development, this novel electronics technology can significantly impact the way we use electronics in our daily life.
< Transformative electronics in soft mode,which becomes wearable for outdoor applications.>
Video Material:
https://youtu.be/im0J18TfShk
Publication: Sang-Hyuk Byun, Joo Yong Sim, Zhanan Zhou, Juhyun Lee, Raza Qazi, Marie C. Walicki, Kyle E. Parker, Matthew P. Haney, Su Hwan Choi, Ahnsei Shon, Graydon B. Gereau, John Bilbily, Shuo Li, Yuhao Liu, Woon-Hong Yeo, Jordan G. McCall, Jianliang Xiao, and Jae-Woong Jeong. 2019. Mechanically transformative electronics, sensors, and implantable devices. Science Advances. Volume 5. No. 11. 12 pages. https://doi.org/10.1126/sciadv.aay0418
Link to download the full-text paper: https://advances.sciencemag.org/content/advances/5/11/eaay0418.full.pdf
Profile: Prof. Jae-Woong Jeong, PhD jjeong1@kaist.ac.kr
https://www.jeongresearch.org/
Professor
Bio-Integrated Electronics and Systems Laboratory
School of Electrical Engineering
Korea Advanced Institute of Science and Technology (KAIST) https://www.kaist.ac.kr
Daejeon 34141, Korea
Profile: Sang-Hyuk Byun, PhD Candidate
shbun95@kaist.ac.kr
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2020.01.31 View 7406 -
Professor Youngseok Ju Awarded the 13th ASAN Award for Young Medical Scientists
Professor Youngseok Ju from the Graduate School of Medical Science and Engineering was selected for the 13th ASAN Award for Young Medical Scientists under the age of 40. Professor Ju will receive 50 million won in prize money.
The ASAN Foundation established this Award in 2007 to encourage young medical scientists who accomplished outstanding achievements in basic and clinical medicine.
The winners are chosen based on a comprehensive assessment of consistency and originality, domestic and international impact, and contributions to medical development and fostering future generations.
Professor Ju is known for having identified the generation principle of cancer genome mutations. In particular, he is recognized for his contributions to the development of cancer prevention, diagnosis, and treatment, by having proven that some cases of lung cancer can occur from destructive changes in chromosomes in lung cells regardless of smoking.
The award ceremony will be held on March 19 in Seoul. The other award will be given to Professor Yong-Ho Lee from the Yonsei University College of Medicine.
2020.01.31 View 4476 -
Scientists Discover the Mechanism of DNA High-Order Structure Formation
(Molecular structures of Abo1 in different energy states (left), Demonstration of an Abo1-assisted histone loading onto DNA by the DNA curtain assay. )
The genetic material of our cells—DNA—exists in a high-order structure called “chromatin”. Chromatin consists of DNA wrapped around histone proteins and efficiently packs DNA into a small volume. Moreover, using a spool and thread analogy, chromatin allows DNA to be locally wound or unwound, thus enabling genes to be enclosed or exposed. The misregulation of chromatin structures results in aberrant gene expression and can ultimately lead to developmental disorders or cancers. Despite the importance of DNA high-order structures, the complexity of the underlying machinery has circumvented molecular dissection.
For the first time, molecular biologists have uncovered how one particular mechanism uses energy to ensure proper histone placement onto DNA to form chromatin. They published their results on Dec. 17 in Nature Communications.
The study focused on proteins called histone chaperones. Histone chaperones are responsible for adding and removing specific histones at specific times during the DNA packaging process. The wrong histone at the wrong time and place could result in the misregulation of gene expression or aberrant DNA replication. Thus, histone chaperones are key players in the assembly and disassembly of chromatin.
“In order to carefully control the assembly and disassembly of chromatin units, histone chaperones act as molecular escorts that prevent histone aggregation and undesired interactions,” said Professor Ji-Joon Song in the Department of Biological Sciences at KAIST. “We set out to understand how a unique histone chaperone uses chemical energy to assemble or disassemble chromatin.”
Song and his team looked to Abo1, the only known histone chaperone that utilizes cellular energy (ATP). While Abo1 is found in yeast, it has an analogous partner in other organisms, including humans, called ATAD2. Both use ATP, which is produced through a cellular process where enzymes break down a molecule’s phosphate bond. ATP energy is typically used to power other cellular processes, but it is a rare partner for histone chaperones.
“This was an interesting problem in the field because all other histone chaperones studied to date do not use ATP,” Song said.
By imaging Abo1 with a single-molecule fluorescence imaging technique known as the DNA curtain assay, the researchers could examine the protein interactions at the single-molecule level. The technique allows scientists to arrange the DNA molecules and proteins on a single layer of a microfluidic chamber and examine the layer with fluorescence microscopy.
The researchers found through real-time observation that Abo1 is ring-shaped and changes its structure to accommodate a specific histone and deposit it on DNA. Moreover, they found that the accommodating structural changes are powered by ADP.
“We discovered a mechanism by which Abo1 accommodates histone substrates, ultimately allowing it to function as a unique energy-dependent histone chaperone,” Song said. “We also found that despite looking like a protein disassembly machine, Abo1 actually loads histone substrates onto DNA to facilitate chromatin assembly.”
The researchers plan to continue exploring how energy-dependent histone chaperones bind and release histones, with the ultimate goal of developing therapeutics that can target cancer-causing misbehavior by Abo1’s analogous human counterpart, ATAD2.
-Profile
Professor Ji-Joon Song
Department of Biological Sciences KI for the BioCentury (https://kis.kaist.ac.kr/index.php?mid=KIB_O) KAIST
2020.01.07 View 10492 -
Professor Shin-Hyun Kim Receives the Young Scientist Award
Professor Shin-Hyun Kim from the Department of Chemical and Biomolecular Engineering received the Young Scientist Award from the Korean Academy of Science and Technology.
The Young Scientist Award is presented to a promising young Korean scientist under the age of 40 who shows significant potential, passion, and remarkable achievement.
Professor Kim was lauded for his research of intelligent soft materials. By applying his research, he developed a capsule sensor material that can not only be used for sensors, but also for displays, color aesthetics, anti-counterfeit technology, residual drug detection, and more.
The award ceremony took place on December 14 at the Gwacheon National Science Museum.
The Korean minister of Science and ICT delivered words of encouragement, reminding everyone that “the driving force behind creative performance of scientists is the provision of continuous support.” He added, “Researchers of Korea deserve greater public attention and support.”
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2019.12.21 View 8070 -
New IEEE Fellow, Professor Jong Chul Ye
Professor Jong Chul Ye from the Department of Bio and Brain Engineering was named a new fellow of the Institute of Electrical and Electronics Engineers (IEEE). IEEE announced this on December 1 in recognition of Professor Ye’s contributions to the development of signal processing and artificial intelligence (AI) technology in the field of biomedical imaging.
As the world’s largest society in the electrical and electronics field, IEEE names the top 0.1% of their members as fellows based on their research achievements.Professor Ye has published more than 100 research papers in world-leading journals in the biomedical imaging field, including those affiliated with IEEE.
He also gave a keynote talk at the yearly conference of the International Society for Magnetic Resonance Imaging (ISMRM) on medical AI technology. In addition, Professor Ye has been appointed to serve as the next chair of the Computational Imaging Technical Committee of the IEEE Signal Processing Society, and the chair of the IEEE Symposium on Biomedical Imaging (ISBI) 2020 to be held in April in Iowa, USA.
Professor Ye said, “The importance of AI technology is developing in the biomedical imaging field. I feel proud that my contributions have been internationally recognized and allowed me to be named an IEEE fellow.”
2019.12.18 View 9893 -
Professor Il-Doo Kim Named Scientist of the Year by the Journalists
Professor Il-Doo Kim from the Department of Materials Science and Engineering was named the 2019 Scientist of the Year by Korean science journalists. The award was conferred at the 2019 Science Press Night ceremony of the Korea Science Journalists Association (KSJA) on November 29.
Professor Kim focuses on developing nanofiber gas sensors for diagnosing diseases in advance by analyzing exhaled biomarkers with electrospinning technology. His outstanding research was praised and selected as one of the top 10 nanotechnology of 2019 by the Korea Nano Technology Research Society (KoNTRS), the Ministry of Science and ICT (MSIT), and the Ministry of Trade, Industry and Energy (MOTIE).
Professor Kim was honored with the QIAN Baojun Fiber Award, which is awarded every two years by Donghua University in Shanghai, China to recognize outstanding contributions in fiber science and technology. Professor Kim was also elected as an academician of the Asia Pacific Academy of Materials (APAM) on November 21 in Guangzhou, China.
In May, Professor Kim was appointed as an associate editor of ACS Nano, a leading international research journal in the field of nanoscience. In his editorial published in the May issue of ACS Nano, Professor Kim introduced and shared the history of KAIST and its vision for the future with other members of the journal. He hopes this will help with promoting a closer relationship between the members of the journal and KAIST moving forward.
“Above all,” he said in his acceptance speech, “the greatest news for me as an educator is that the first PhD graduate from our lab, Dr. Seonjin Choi, was appointed as the youngest professor in the Division of Materials Science and Engineering at Hanyang University on September 1.”
2019.12.17 View 11287 -
KAIST Awarded the IPBC R&D Institution Team of the Year
KAIST was awarded the R&D Institution Team of the Year during the annual IPBC (Intellectual Property Business Congress) Asia 2019 held in Tokyo October 28-30. IPBC is a conference dedicated to IP value creation strategies hosted by IAM Media, a world’s leading IP business media platform.
IPBC Asia 2019 recognized the institutions and businesses that employed innovative IP strategies and management to produce the greatest IP value in 11 categories covering automotive, electronics, healthcare and biotechnology, internet and software, R&D institutions, semiconductors, industrials, mobile and telecommunications, Asia IP deals, Asia teams, and Asia individuals. This year, KAIST was recognized as one of the most active patentees in the Asia-Pacific region by significantly increasing its IP value through licensing and tech transfers.
Associate Vice President Kyung Cheol Choi of the Office of University-Industry Cooperation remarked, “We are so delighted to prove the strong research capacity of KAIST. This will help us accomplish our vision of being a leading university that creates global impact.”
2019.12.04 View 8010 -
Tungsten Suboxide Improves the Efficiency of Platinum in Hydrogen Production
< PhD Candidate Jinkyu Park and Professor Jinwoo Lee >
Researchers presented a new strategy for enhancing catalytic activity using tungsten suboxide as a single-atom catalyst (SAC). This strategy, which significantly improves hydrogen evolution reaction (HER) in metal platinum (pt) by 16.3 times, sheds light on the development of new electrochemical catalyst technologies.
Hydrogen has been touted as a promising alternative to fossil fuels. However, most of the conventional industrial hydrogen production methods come with environmental issues, releasing significant amounts of carbon dioxide and greenhouse gases.
Electrochemical water splitting is considered a potential approach for clean hydrogen production. Pt is one of the most commonly used catalysts to improve HER performance in electrochemical water splitting, but the high cost and scarcity of Pt remain key obstacles to mass commercial applications.
SACs, where all metal species are individually dispersed on a desired support material, have been identified as one way to reduce the amount of Pt usage, as they offer the maximum number of surface exposed Pt atoms.
Inspired by earlier studies, which mainly focused on SACs supported by carbon-based materials, a KAIST research team led by Professor Jinwoo Lee from the Department of Chemical and Biomolecular Engineering investigated the influence of support materials on the performance of SACs.
Professor Lee and his researchers suggested mesoporous tungsten suboxide as a new support material for atomically dispersed Pt, as this was expected to provide high electronic conductivity and have a synergetic effect with Pt.
They compared the performance of single-atom Pt supported by carbon and tungsten suboxide respectively. The results revealed that the support effect occurred with tungsten suboxide, in which the mass activity of a single-atom Pt supported by tungsten suboxide was 2.1 times greater than that of single-atom Pt supported by carbon, and 16.3 times higher than that of Pt nanoparticles supported by carbon.
The team indicated a change in the electronic structure of Pt via charge transfer from tungsten suboxide to Pt. This phenomenon was reported as a result of strong metal-support interaction between Pt and tungsten suboxide.
HER performance can be improved not only by changing the electronic structure of the supported metal, but also by inducing another support effect, the spillover effect, the research group reported. Hydrogen spillover is a phenomenon where adsorbed hydrogen migrates from one surface to another, and it occurs more easily as the Pt size becomes smaller.
The researchers compared the performance of single-atom Pt and Pt nanoparticles supported by tungsten suboxide. The single-atom Pt supported by tungsten suboxide exhibited a higher degree of hydrogen spillover phenomenon, which enhanced the Pt mass activity for hydrogen evolution up to 10.7 times compared to Pt nanoparticles supported by tungsten suboxide.
Professor Lee said, “Choosing the right support material is important for improving electrocatalysis in hydrogen production. The tungsten suboxide catalyst we used to support Pt in our study implies that interactions between the well-matched metal and support can drastically enhance the efficiency of the process.”
This research was supported by the Ministry of Science and ICT and introduced in the International Edition of the German journal Angewandte Chemie.
Figure. Schematic representation of hydrogen evolution reaction (HER) of pseudo single-atom Pt supported by tungsten suboxide
-Publication
Jinkyu Park, Dr. Seonggyu Lee, Hee-Eun Kim, Ara Cho, Seongbeen Kim, Dr. Youngjin Ye, Prof. Jeong Woo Han, Prof. Hyunjoo Lee, Dr. Jong Hyun Jang, and Prof. Jinwoo Lee. 2019. Investigation of the Support Effect in Atomically Dispersed Pt on WO3−x for Utilization of Pt in the Hydrogen Evolution Reaction. International Edition of Angewandte Chemie. Volume No. 58. Issue No. 45. 6 pages. https://doi.org/10.1002/anie.201908122
-ProfileProfessor Jinwoo LeeConvergence of Energy and Nano Science Laboratoryhttp://cens.kaist.ac.kr
Department of Chemical and Biomolecular EngineeringKAIST
2019.10.28 View 21096 -
A Single, Master Switch for Sugar Levels?
When a fly eats sugar, a single brain cell sends simultaneous messages to stimulate one hormone and inhibit another to control glucose levels in the body. Further research into this control system with remarkable precision could shed light on the neural mechanisms of diabetes and obesity in humans .
A single neuron appears to monitor and control sugar levels in the fly body, according to research published this week in Nature. This new insight into the mechanisms in the fly brain that maintain a balance of two key hormones controlling glucose levels, insulin and glucagon, can provide a framework for understanding diabetes and obesity in humans.
Neurons that sense and respond to glucose were identified more than 50 years ago, but what they do in our body has remained unclear. Researchers at the Korea Advanced Institute of Science and Technology (KAIST) and New York University School of Medicine have now found a single “glucose-sensing neuron” that appears to be the master controller in Drosophila, the vinegar fly, for maintaining an ideal glucose balance, called homeostasis.
Professor Greg Seong-Bae Suh, Dr. Yangkyun Oh and colleagues identified a key neuron that is excited by glucose, which they called CN neuron. This CN neuron has a unique shape – it has an axon (which is used to transmit information to downstream cells) that is bifurcated. One branch projects to insulin-producing cells, and sends a signal triggering the secretion of the insulin equivalent in flies. The other branch projects to glucagon-producing cells and sends a signal inhibiting the secretion of the glucagon equivalent.
When flies consume food, the levels of glucose in their body increase; this excites the CN neuron, which fires the simultaneous signals to stimulate insulin and inhibit glucagon secretion, thereby maintaining the appropriate balance between the hormones and sugar in the blood. The researchers were able to see this happening in the brain in real time by using a combination of cutting-edge fluorescent calcium imaging technology, as well as measuring hormone and sugar levels and applying highly sophisticated molecular genetic techniques.
When flies were not fed, however, the researchers observed a reduction in the activity of CN neuron, a reduction in insulin secretion and an increase in glucagon secretion. These findings indicate that these key hormones are under the direct control of the glucose-sensing neuron. Furthermore, when they silenced the CN neuron rendering dysfunctional CN neuron in flies, these animals experienced an imbalance, resulting in hyperglycemia – high levels of sugars in the blood, similar to what is observed in diabetes in humans. This further suggests that the CN neuron is critical to maintaining glucose homeostasis in animals.
While further research is required to investigate this process in humans, Suh notes this is a significant step forward in the fields of both neurobiology and endocrinology.
“This work lays the foundation for translational research to better understand how this delicate regulatory process is affected by diabetes, obesity, excessive nutrition and diets high in sugar,” Suh said.
Profile: Greg Seong-Bae Suh
seongbaesuh@kaist.ac.kr
Professor Department of Biological Sciences
KAIST
(Figure: A single glucose-excited CN neuron extends bifurcated axonal branches,
one of which innervates insulin producing cells and stimulates their activity an the other axonal branch projects to glucagon producing cells and inhibits their activity.)
2019.10.24 View 17632 -
A Mathematical Model Reveals Long-Distance Cell Communication Mechanism
How can tens of thousands of people in a large football stadium all clap together with the same beat even though they can only hear the people near them clapping?
A combination of a partial differential equation and a synthetic circuit in microbes answers this question. An interdisciplinary collaborative team of Professor Jae Kyoung Kim at KAIST, Professor Krešimir Josić at the University of Houston, and Professor Matt Bennett at Rice University has identified how a large community can communicate with each other almost simultaneously even with very short distance signaling. The research was reported at Nature Chemical Biology.
Cells often communicate using signaling molecules, which can travel only a short distance. Nevertheless, the cells can also communicate over large distances to spur collective action. The team revealed a cell communication mechanism that quickly forms a network of local interactions to spur collective action, even in large communities.
The research team used an engineered transcriptional circuit of combined positive and negative feedback loops in E. coli, which can periodically release two types of signaling molecules: activator and repressor. As the signaling molecules travel over a short distance, cells can only talk to their nearest neighbors. However, cell communities synchronize oscillatory gene expression in spatially extended systems as long as the transcriptional circuit contains a positive feedback loop for the activator.
Professor Kim said that analyzing and understanding such high-dimensional dynamics was extremely difficult. He explained, “That’s why we used high-dimensional partial differential equation to describe the system based on the interactions among various types of molecules.” Surprisingly, the mathematical model accurately simulates the synthesis of the signaling molecules in the cell and their spatial diffusion throughout the chamber and their effect on neighboring cells.
The team simplified the high-dimensional system into a one-dimensional orbit, noting that the system repeats periodically. This allowed them to discover that cells can make one voice when they lowered their own voice and listened to the others. “It turns out the positive feedback loop reduces the distance between moving points and finally makes them move all together. That’s why you clap louder when you hear applause from nearby neighbors and everyone eventually claps together at almost the same time,” said Professor Kim.
Professor Kim added, “Math is a powerful as it simplifies complex thing so that we can find an essential underlying property. This finding would not have been possible without the simplification of complex systems using mathematics."
The National Institutes of Health, the National Science Foundation, the Robert A. Welch Foundation, the Hamill Foundation, the National Research Foundation of Korea, and the T.J. Park Science Fellowship of POSCO supported the research.
(Figure: Complex molecular interactions among microbial consortia is simplified as interactions among points on a limit cycle (right).)
2019.10.15 View 27089