research
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A Firefighter Drone That Flies and Crawls Up Walls
KAIST researchers developed a wall-climbing scout drone to fight fires in high-rises, finding the source of the fires and locating people trapped inside.
The 1974 American disaster film Towering Inferno depicted well the earnest struggles of firefighters engaged in ending a fire at a 138-story skyscraper. To this day, fires at high-rise buildings are considered one of the most dangerous disasters.
Skyscraper fires are particularly difficult to contain because of their ability to spread rapidly in high-occupant density spaces and the challenge of fighting fires in the buildings’ complex vertical structure. Accessibility to skyscrapers at the time of the fire is limited, and it is hard to assess the initial situation.
A research team at KAIST led by Professor Hyun Myung of the Civil and Environmental Engineering Department developed an unmanned aerial vehicle, named the Fireproof Aerial RObot System (FAROS), which detects fires in skyscrapers, searches the inside of the building, and transfers data in real time from fire scenes to the ground station.
As an extended version of Climbing Aerial RObot System (CAROS) that was created in 2014 by the research team, the FAROS can also fly and climb walls.
The FAROS, whose movements rely on a quadrotor system, can freely change its flight mode into a spider’s crawling on walls, and vice versa, facilitating unimpeded navigation in the labyrinth of narrow spaces filled with debris and rubble inside the blazing building.
The drone “estimates” its pose by utilizing a 2-D laser scanner, an altimeter, and an Inertia Measurement Unit sensor to navigate autonomously. With the localization result and using a thermal-imaging camera to recognize objects or people inside a building, the FAROS can also detect and find the fire-ignition point by employing dedicated image-processing technology.
The FAROS is fireproof and flame-retardant. The drone’s body is covered with aramid fibers to protect its electric and mechanical components from the direct effects of the flame. The aramid fiber skin also has a buffer of air underneath it, and a thermoelectric cooling system based on the Peltier effect to help maintain the air layer within a specific temperature range.
The research team demonstrated the feasibility of the localization system and wall-climbing mechanism in a smoky indoor environment. The fireproof test showed that the drone could endure the heat of over 1,000° Celsius from butane gas and ethanol aerosol flames for over one minute.
Professor Myung said, “As cities become more crowded with skyscrapers and super structures, fire incidents in these high-rise buildings are life-threatening massive disasters. The FAROS can be aptly deployed to the disaster site at an early stage of such incidents to minimize the damage and maximize the safety and efficiency of rescue mission.”
The research team has recently started to enhance the performance of the fireproof design for the exteroceptive sensors including a 2-D laser scanner and a thermal-imaging camera because those sensors could be more exposed to fire than other inside sensors and electric components.
This research was funded by the KAIST Initiative for Disaster Studies and the KAIST Institute.
YouTube link: https://youtu.be/gPNRZi0EPQw
Picture 1: Demonstration of Wall-climbing
The Fireproof Aerial RObot System (FAROS) is a wall-climbing scout drone developed to conduct explorations into the site of skyscraper fires. It has an ability to climb walls in smoky, narrow spaces inside buildings.
Figure 2: An Ability to Withstand Fires
The FAROS can endure the heat of over 1,000° Celsius from butane gas and ethanol aerosol flames for over one minute.
2016.01.20 View 14680 -
An App to Digitally Detox from Smartphone Addiction: Lock n' LOL
KAIST researchers have developed an application that helps people restrain themselves from using smartphones during meetings or social gatherings.
The app’s group limit mode enforces users to curtail their smartphone usage through peer-pressure while offering flexibility to use the phone in an emergency.
When a fake phone company released its line of products, NoPhones, a thin, rectangular-shaped plastic block that looked just like a smartphone but did not function, many doubted that the simulated smartphones would find any users. Surprisingly, close to 4,000 fake phones were sold to consumers who wanted to curb their phone usage.
As smartphones penetrate every facet of our daily lives, a growing number of people have expressed concern about distractions or even the addictions they suffer from overusing smartphones.
Professor Uichin Lee of the Department of Knowledge Service Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and his research team have recently introduced a solution to this problem by developing an application, Lock n’ LoL (Lock Your Smartphone and Laugh Out Loud), to help people lock their smartphones altogether and keep them from using the phone while engaged in social activities such as meetings, conferences, and discussions.
Researchers note that the overuse of smartphones often results from users’ habitual checking of messages, emails, or other online contents such as status updates in social networking service (SNS). External stimuli, for example, notification alarms, add to smartphone distractions and interruptions in group interactions.
The Lock n’ LoL allows users to create a new room or join an existing room. The users then invite meeting participants or friends to the room and share its ID with them to enact the Group Limit (lock) mode. When phones are in the lock mode, all alarms and notifications are automatically muted, and users must ask permission to unlock their phones. However, in an emergency, users can access their phones for accumulative five minutes in a temporary unlimit mode.
In addition, the app’s Co-location Reminder detects and lists nearby users to encourage app users to limit their phone use. The Lock n’ LoL also displays important statistics to monitor users’ behavior such as the current week’s total limit time, the weekly average usage time, top friends ranked by time spent together, and top activities in which the users participated.
Professor Lee said,
“We conducted the Lock n’ LoL campaign throughout the campus for one month this year with 1,000 students participating. As a result, we discovered that students accumulated more than 10,000 free hours from using the app on their smartphones. The students said that they were able to focus more on their group activities. In an age of the Internet of Things, we expect that the adverse effects of mobile distractions and addictions will emerge as a social concern, and our Lock n’ LoL is a key effort to address this issue.”
He added, “This app will certainly help family members to interact more with each other during the holiday season.”
The Lock n’ LoL is available for free download on the App Store and Google Play: https://itunes.apple.com/lc/app/lock-n-lol/id1030287673?mt=8.
YouTube link: https://youtu.be/1wY2pI9qFYM
Figure 1: User Interfaces of Lock n’ LoL
This shows the final design of Lock n’ LoL, which consists of three tabs: My Info, Friends, and Group Limit Mode. Users can activate the limit mode by clicking the start button at the bottom of the screen.
Figure 2: Statistics of Field Deployment
This shows the deployment summary of Lock n’ LoL campaign in May 2015.
2015.12.17 View 9806 -
KAIST Develops New Technique for Chiral Activity in Molecules
Professor Hyunwoo Kim of the Chemistry Department and his research team have developed a technique that can easily analyze the optical activity of charged compounds by using nuclear magnetic resonance (NMR) spectroscopy. The research finding entitled “H NMR Chiral Analysis of Charged Molecules via Ion Pairing with Aluminum Complexes” was published online in the October 19th issue of The Journal of the American Chemical Society.
The technique relies on observation of the behavior of optical isomers. Molecules with the same composition that are mirror images of each other are optical isomers. For example, the building blocks of all living organisms, amino acids, are a single optical isomer. In our bodies, optical isomers bring different physiological changes due to their distinct optical activities. Therefore, controlling and analyzing the optical activities are critical when developing a new drug.
High-performance liquid chromatography (HPLC) is the de facto standard of analyzing the optical activity of a compound. However, HPLC is very expensive that many laboratories can’t afford to have. In addition, with the machine, one analysis may take 30 minutes to one hour to complete. It lacks in signal sensitivity and chemical decomposition, and the application is limited to nonpolar compounds.
Usually adopted in analyzing the structure of a chemical compound, NMR spectroscopy requires only one to five minutes per single analysis. Since it is essential for analyzing the molecular structure, many chemistry labs have NMR equipment. However, until this technique was invented, no other research team had reported an effective way of using the NMR spectroscopy to decompose the signal of chiral activity of a compound.
The research team uses negatively-charged metal compounds in NMR spectroscopy. The technique employs negatively-charged metal compounds which bond ionically to positively- and negatively-charged optical compounds. As a result, the NMR spectroscopy can distinguish the signal from chiral activity. Not only can it analyze various chemicals without structural constraints, but it can also be used for both nonpolar and polar solvents.
As many compounds for new drugs have functional groups, which can be charged, this analysis method can be directly employed in the development process of drugs. Professor Kim said, “A revolutionary analysis method has been developed using simple chemical principles. I hope that our method will be applied to the development of new medicine.”
This research was sponsored by the Center for Nanomaterials and Chemical Reactions at the Institute for Basic Science and the Supercomputing Research Center of KAIST.
Picture 1: Separations of NMR Signals of Chemicals due to Interaction with Metal Compounds
Picture 2: Separations of NMR Signals in Different Chemicals
2015.11.20 View 10867 -
A New Way to Look at MOFs
An international research team composed of researchers from KAIST (led by Professors Osamu Terasaki and Jeung Ku Kang at the Graduate School of Energy, Environment, Water and Sustainability) and other universities, including UC Berkeley, has recently published research results on the adsorption process of metal-organic frameworks (MOFs) in Nature (November 9, 2015).
MOFs are porous three-dimensional crystals with a high internal surface area, which have a wide range of applications involving adsorption such as hydrogen, methane, or carbon dioxide storage. In the paper entitled “Extra Adsorption and Adsorbate Superlattice Formation in Metal-organic Frameworks,” the research team described their observation of a very specific interpore interaction process in MOFs.
For additional information, please see:
A New Way to Look at MOFs
International study challenges prevailing view on how metal organic frameworks store gases
EurekAlert, November 9, 2015
http://www.eurekalert.org/pub_releases/2015-11/dbnl-anw110915.php
(Courtesy of the US Department of Energy and Lawrence Berkeley National Laboratory news release)
2015.11.13 View 7764 -
Using Light to Treat Alzheimer's Disease
Medical application of photoactive chemicals offers a promising therapeutic strategy for neurodegenerative diseases.
A research team jointly led by Professor Chan Beum Park of the Materials Science and Engineering Department at KAIST and Dr. Kwon Yu from the Bionano Center at the Korea Research Institute of Bioscience and Biotechnology (KRIBB) conducted research to suppress an abnormal assembly of beta-amyloids, a protein commonly found in the brain, by using photo-excited porphyrins.
Beta-amyloid plaques are known to cause Alzheimer's disease. This research finding suggests new ways to treat neurodegenerative illnesses including Alzheimer's disease. It was published online as the lead article in the September 21th issue of Angewandte Chemie. The title of the article is “Photo-excited Porphyrins as a Strong Suppressor of ß-Amyloid Aggregation and Synaptic Toxicity.”
Light-induced treatments using organic photosensitizers have advantages to managing the treatment in time and area. In the case of cancer treatments, doctors use photodynamic therapies where a patient is injected with an organic photosensitizer, and a light is shed on the patient’s lesion. However, such therapies had never been employed to treat neurodegenerative diseases.
Alzheimer's starts when a protein called beta-amyloid is created and deposited in a patient’s brain. The abnormally folded protein created this way harms the brain cells by inducing the degradation of brain functions, for example, dementia. If beta-amyloid creation can be suppressed at an early stage, the formation of amyloid deposits will stop. This could prevent Alzheimer’s disease or halt its progress.
The research team effectively prevented the buildup of beta-amyloids by using blue LED lights and a porphyrin inducer, which is a biocompatible organic compound. By absorbing light energy, a photosensitizer such as porphyrin reaches the excitation state. Active oxygen is created as the porphyrin returns to its ground state. The active oxygen oxidizes a beta-amyloid monomer, and by combining with it, disturbs its assembly.
The technique was tested on drosophilae or fruit flies, which were produced to model Alzheimer on invertebrates. The research showed that symptoms of Alzheimer's disease in the fruit flies such as damage on synapse and muscle, neuronal apoptosis, degradation in motility, and decreased longevity were alleviated. Treatments with light provide additional benefits: less medication is needed than other drug treatments, and there are fewer side effects. When developed, photodynamic therapy will be used widely for this reason.
Professor Park said, “This work has significance as it was the first case to use light and photosensitizers to stop deposits of beta-amyloids. We plan to carry the research further by testing compatibility with other organic and inorganic photosensitizers and by changing the subject of photodynamic therapy to vertebrate such as mice.”
Picture 1 – Deposits of Beta-Amyloid in Fruit Flies Stopped by Using Porphyrin and Blue LED Lights
Picture 2 – The Research Finding Published as the Lead Article in Angewandte Chemie (September 2015)
2015.11.11 View 10526 -
Membrane
Scientists at KAIST have developed a new way of making fuel cell membranes using nanoscale fasteners, paving the way for lower-cost, higher-efficiency and more easily manufactured fuel cells.
The internal workings of fuel cells vary, but basically all types mix hydrogen and oxygen to produce a chemical reaction that delivers usable electricity and exhausts ordinary water as a by-product. One of the most efficient types is the proton exchange membrane (PEM) fuel cell, which operates at low enough temperatures to be used in homes and vehicles.
To generate electricity, PEM fuel cells rely on two chemical compartments separated by a permeable catalyst membrane. This membrane acts as an electrolyte; a negative electrode is bonded to one side of the membrane and a positive electrode is bonded to the other. The electrolyte membrane is often based on a polymer of perfluorosulfonic acid. Due to its high cost, however, a less expensive hydrocarbon-based electrolyte membrane has attracted interest in this technology sector.
Until now, the challenge in adopting such a hydrocarbon membrane has been that the interface between the electrode and hydrocarbon membrane is weak. This causes the membrane to delaminate relatively easily, falling apart and losing efficiency with use.
Professor Hee-Tak Kim of the Department of Chemical and Biomolecular Engineering at the Korea Advanced Institute of Science and Technology (KAIST) and his research team have developed a new fastening system that bonds the two materials mechanically rather than chemically. This opens the way to the development of fuel cell membranes that are less expensive, easier to manufacture, stronger and more efficient.
The researchers achieved this by moulding a pattern of tiny cylindrical pillars on the face of the hydrocarbon membrane. The pillars protrude into a softened skin of the electrode with heat. The mechanical bond sets and strengthens as the material cools and absorbs water. The pillar-patterned hydrocarbon membrane is cast using silicone moulds.
Professor Kim said, “This physically fastened bond is almost five times stronger and harder to separate than current bonds between the same layers.”
The new interlocking method also appears to offer a way to bond many types of hydrocarbon membranes that, until now, have been rejected because they couldn’t be fastened robustly. This would make hydrocarbon membranes practical for a number of applications beyond fuel cells such as rechargeable “redox flow” batteries.
The research team is now developing a stronger and more scalable interlocking interface for their nanoscale fasteners.
Picture: Schematic Diagram of the Fabrication of the Pillar P-SPAES Membrane and Its Working Principle of Interlocking Effects
2015.11.06 View 9700 -
Mapping the Folding Process of a Single Membrane Protein
KAIST and UCLA scientists were able to observe an individual membrane protein fold and unfold by pulling and releasing magnetically trapped protein molecules.
Proteins are huge molecules containing hundreds to thousands of atoms that adopt a unique three dimensional structure, placing chemical groups in just the right place to catalyze reactions or build cellular structures. How all those atoms manage to find the right location - the so-called folding problem - has fascinated molecular biologists since the first structures were seen in the 1950s. Moreover, folding has important medical implications because most genetic defects cause protein misfolding.
About a third of all proteins float around in the cell membrane where they ensure the right chemicals get in the cell in the right amounts. Membrane proteins also provide key information links between the cell and its environment. Indeed, most drugs target membrane proteins. Nevertheless, the folding of membrane proteins has been particularly difficult to study and has rarely been studied in natural environments, leaving the folding process for a large fraction of the protein universe still largely cloaked in mystery.
In a recent issue of Nature Chemical Biology, published on October 19, 2015, a research team led by Tae-Young Yoon of the Department of Physics at the Korea Advanced Institute of Science and Technology (KAIST) and James U. Bowie of the Department of Chemistry and Biochemistry at the University of California, Los Angeles (UCLA), report a new method for manipulating the folding of membrane proteins in a membrane environment using a tool called a magnetic tweezer.
Researchers first attach long DNA handles to the ends of the protein. One handle is attached to a glass surface and the other to a magnetic bead. Using a magnet, they can essentially grab the protein and pull on it, inducing it to unfold. By playing with the bead attached to the protein, they can force the protein to unfold or allow it to refold, and watch all this happening by 3D-tracking of the magnetic bead. With this novel strategy, they were able to quantitatively map the folding energy landscape, the folding kinetic rate, and folding intermediates of a membrane protein in a membrane environment for the first time.
“I have been dreaming about this experiment for a decade. To see it work so well is really gratifying,” said Dr. Bowie.
One of the major surprises in the study was that essentially all the atoms of the protein jump into the correct structure together. The researchers expected that the protein structure would come together in a more piecemeal fashion, with different parts of the structure forming separately, but that was not the case. It is possible that nature evolved such a smooth, highly cooperative folding process to prevent partially folded forms that could get into trouble in the crowded cell membrane. On the other hand, the cooperative folding seen here might not apply to other membrane proteins.
“We need to look at more proteins. The technique developed here may allow us to do just that,” said Dr. Yoon.
The single molecule mechanical manipulation technique could enable detailed folding studies of many other membrane proteins. A major barrier to the study of membrane proteins previously is that the proteins tend to stick together and get tangled up, as computer cords lying at your feet tend to do. With the tweezer technique used in this work, the protein cords are held apart from other cords so they can’t get knotted up. It is hoped that the new approach will open up an important part of the protein universe to scrutiny, including many proteins that become misfolded in disease states.
The title of the research paper is “Mapping the energy landscape for second-stage folding of a single membrane protein” (DOI: 10.1038/nchembio.1939).
Picture: Single-molecule magnetic tweezers that induce mechanical unfolding and refolding of a single membrane protein. Since the force applied is parallel to the biological lipid membrane, the unfolding and refolding processes occur within the membrane.
2015.10.20 View 9235 -
Establishment of System Metabolic Engineering Strategies
Although conventional petrochemical processes have generated chemicals and materials which have been useful to mankind, they have also triggered a variety of environmental problems including climate change and relied too much on nonrenewable natural resources. To ameliorate this, researchers have actively pursued the development of industrial microbial strains around the globe in order to overproduce industrially useful chemicals and materials from microbes using renewable biomass. This discipline is called metabolic engineering.
Thanks to advances in genetic engineering and our knowledge of cellular metabolism, conventional metabolic engineering efforts have succeeded to a certain extent in developing microbial strains that overproduce bioproducts at an industrial level. However, many metabolic engineering projects launched in academic labs do not reach commercial markets due to a failure to fully integrate industrial bioprocesses.
In response to this, Distinguished Professor Sang Yup Lee and Dr. Hyun Uk Kim, both from the Department of Chemical and Biomolecular Engineering at KAIST, have recently suggested ten general strategies of systems metabolic engineering to successfully develop industrial microbial strains. Systems metabolic engineering differs from conventional metabolic engineering by incorporating traditional metabolic engineering approaches along with tools of other fields, such as systems biology, synthetic biology, and molecular evolution.
The ten strategies of systems metabolic engineering have been featured in Nature Biotechnology released online in October 2015, which is entitled "Systems strategies for developing industrial microbial strains."
The strategies cover economic, state-of-the-art biological techniques and traditional bioprocess aspects. Specifically, they consist of: 1) project design including economic evaluation of a target bioproduct; 2) selection of host strains to be used for overproduction of a bioproduct; 3) metabolic pathway reconstruction for bioproducts that are not naturally produced in the selected host strains; 4) increasing tolerance of a host strain against the bioproduct; 5) removing negative regulatory circuits in the microbial host limiting overproduction of a bioproduct; 6) rerouting intracellular fluxes to optimize cofactor and precursor availability necessary for the bioproduct formation; 7) diagnosing and optimizing metabolic fluxes towards product formation; 8) diagnosis and optimization of microbial culture conditions including carbon sources; 9) system-wide gene manipulation to further increase the host strain's production performance using high-throughput genome-scale engineering and computational tools; and 10) scale-up fermentation of the developed strain and diagnosis for the reproducibility of the strain's production performance.
These ten strategies were articulated with successful examples of the production of L-arginine using Corynebacterium glutamicum, 1,4-butanediol using Escherichia coli, and L-lysine and bio-nylon using C. glutamicum.
Professor Sang Yup Lee said, "At the moment, the chance of commercializing microbial strains developed in academic labs is very low. The strategies of systems metabolic engineering outlined in this analysis can serve as guidelines when developing industrial microbial strains. We hope that these strategies contribute to improving opportunities to commercialize microbial strains developed in academic labs with drastically reduced costs and efforts, and that a large fraction of petroleum-based processes will be replaced with sustainable bioprocesses."
Lee S. Y. & Kim, H. U. Systems Strategies for Developing Industrial Microbial Strains. Nature Biotechnology (2015).
This work was supported by the Technology Development Program to Solve Climate Change on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556) and by the Intelligent Synthetic Biology Center through the Global Frontier Project (2011-0031963) from the Ministry of Science, ICT and Future Planning (MSIP), Korea, and through the National Research Foundation (NRF) of Korea. This work was also supported by the Novo Nordisk Foundation.
Picture: Concept of the Systems Metabolic Engineering Framework
(a) Three major bioprocess stages (b) Considerations in systems metabolic engineering to optimize the whole bioprocess. List of considerations for the strain development and fermentation contribute to improving microbial strain's production performance (red), whereas those for the separation and purification help in reducing overall operation costs by facilitating the downstream process (blue). Some of the considerations can be repeated in the course of systems metabolic engineering.
2015.10.19 View 9769 -
Discovery of Redox-Switch of KEenzyme Involved in N-Butanol Biosynthesis
Research teams at KAIST and Kyungpook National University (KNU) have succeeded in uncovering the redox-switch of thiolase, a key enzyme for n-butanol production in Clostridium acetobutylicum, one of the best known butanol-producing bacteria.
Biological n-butanol production was first reported by Louis Pasteur in 1861, and the bioprocess was industrialized usingClostridium acetobutylicum. The fermentation process by Clostridium strains has been known to be the most efficient one for n-butanol production. Due to growing world-wide issues such as energy security and climate change, the biological production of n-butanol has been receiving much renewed interest. This is because n-butanol possesses much better fuel characteristics compared to ethanol, such as higher energy content (29.2 MJ/L vs 19.6 MJ/L), less corrosiveness, less hygroscopy, and the ease with which it can be blended with gasoline and diesel.
In the paper published in Nature Communications, a broad-scope, online-only, and open access journal issued by the Nature Publishing Group (NPG), on September 22, 2015, Professor Kyung-Jin Kim at the School of Life Sciences, KNU, and Distinguished Professor Sang Yup Lee at the Department of Chemical and Biomolecular Engineering, KAIST, have proved that the redox-switch of thiolase plays a role in a regulation of metabolic flux in C. acetobutylicum by using in silico modeling and simulation tools.
The research team has redesigned thiolase with enhanced activity on the basis of the 3D structure of the wild-type enzyme. To reinforce a metabolic flux toward butanol production, the metabolic network of C. acetobutylicum strain was engineered with the redesigned enzyme. The combination of the discovery of 3D enzyme structure and systems metabolic engineering approaches resulted in increased n-butanol production in C. acetobutylicum, which allows the production of this important industrial chemical to be cost competitive.
Professors Kim and Lee said, "We have reported the 3D structure of C. acetobutylicum thiolase-a key enzyme involved in n-butanol biosynthesis, for the first time. Further study will be done to produce butanol more economically on the basis of the 3D structure of C. acetobutylicum thiolase."
This work was published online in Nature Communications on September 22, 2015.
Reference: Kim et al. "Redox-switch regulatory mechanism of thiolase from Clostridium acetobutylicum," Nature Communications
This research was supported by the Technology Development Program to Solve Climate Changes from the Ministry of Education, Science and Technology (MEST), Korea, the National Research Foundation of Korea, and the Advanced Biomass Center through the Global Frontier Research Program of the MEST, Korea.
For further information, contact Dr. Sang Yup Lee, Distinguished Professor, KAIST, Daejeon, Korea (leesy@kaist.ac.kr, +82-42-350-3930); and Dr. Kyung-Jin Kim, Professor, KNU, Daegu, Korea (kkim@knu.ac.kr, +82-53-950-6088).
Figure 1: A redox-switch of thiolase involves in butanol biosynthesis in Clostridium acetobutylicum. Thiolase condenses two acetyl-CoA molecules for initiating four carbon flux towards butanol.
Figure 2: Thiolase catalyzes the condensation reaction of acetyl-CoA to acetoacetyl-CoA. Two catalytic cysteine residues at 88th and 378th are oxidized and formed an intermolecular disulfide bond in an oxidized status, which results in inactivation of the enzyme for n-butanol biosynthesis. The intermolecular disulfide bond is broken enabling the n-butanol biosynthesis, when the environment status is reduced.
2015.09.23 View 9804 -
KAIST's Mathematician Reveals the Mechanism for Sustaining Biological Rhythms
Our bodies have a variety of biological clocks that follow rhythms or oscillations with periods ranging from seconds to days. For example, our hearts beat every second, and cells divide periodically. The circadian clock located in the hypothalamus generates twenty-four hour rhythms, timing our sleep and hormone release. How do these biological clocks or circuits generate and sustain the stable rhythms that are essential to life?
Jae Kyoung Kim, who is an assistant professor in the Department of Mathematical Sciences at KAIST, has predicted how these biological circuits generate rhythms and control their robustness, utilizing mathematical modeling based on differential equations and stochastic parameter sampling. Based on his prediction, using synthetic biology, a research team headed by Matthew Bennett of Rice University constructed a novel biological circuit that spans two genetically engineered strains of bacteria, one serves as an activator and the other as a repressor to regulate gene expression across multiple cell types, and found that the circuit generates surprisingly robust rhythms under various conditions.
The results of the research conducted in collaboration with KAIST (Korea Institute of Science and Technology), Rice University, and the University of Houston were published in Science (August 28, 2015 issue). The title of the paper is "Emergent Genetic Oscillations in a Synthetic Microbial Consortium" .
The top-down research approach, which focuses on identifying the components of biological circuits, limits our understanding of the mechanisms in which the circuits generate rhythms. Synthetic biology, a rapidly growing field at the interface of biosciences and engineering, however, uses a bottom-up approach.
Synthetic biologists can create complex circuits out of simpler components, and some of these new genetic circuits are capable of fluctuation to regulate gene production. In the same way that electrical engineers understand how an electrical circuit works as they construct batteries, resistors, and wires, synthetic biologists can understand better about biological circuits if they put them together using genes and proteins. However, due to the complexity of biological systems, both experiments and mathematical modeling need to be applied hand in hand to design these biological circuits and understand their function.
In this research, an interdisciplinary approach proved that a synthetic intercellular singling circuit generates robust rhythms to create a cooperative microbial system. Specifically, Kim's mathematical analysis suggested, and experiments confirmed, that the presence of negative feedback loops in addition to a core transcriptional negative feedback loop can explain the robustness of rhythms in this system. This result provides important clues about the fundamental mechanism of robust rhythm generation in biological systems.
Furthermore, rather than constructing the entire circuit inside a single bacterial strain, the circuit was split among two strains of Escherichia coli bacterium. When the strains were grown together, the bacteria exchanged information, completing the circuit. Thus, this research also shows how, by regulating individual cells within the system, complex biological systems can be controlled, which in turn influences each other (e.g., the gut microbiome in humans).
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Ye Chen, a graduate student in Bennett's laboratory at Rice University, and Jae Kyoung Kim, an assistant professor at KAIST and a former postdoctoral fellow at Ohio State University, are the lead authors of the paper. The co-authors are Rice graduate student Andrew Hirning and Krešimir Josic?, a professor of mathematics at the University of Houston. Bennett is the Assistant Professor of the Biochemistry and Cell Biology Department at Rice University.
About the researcher: While Jae Kyoung Kim is a mathematician, he has also solved various biological puzzles in collaboration with various experimental laboratories of Matthew Bennett at Rice University, David Virshup at Duke and the National University of Singapore, Carla Finkielstein at Virginia Polytechnic Institute and State University, Choo-Gon Lee at the Florida State University, Seung-Hee Yoo at the Medical School of the University of Texas, Toru Takumi at RIKEN Brain Science Institute, and Travis Wager at Pfizer Inc. He has used non-linear dynamics and stochastic analysis to understand the function of biochemical networks in biological systems. In particular, he is interested in mechanisms generating and regulating biological rhythms.
Picture 1: This schematic image is the design of a biological circuit between two strains of bacteria and the part of differential equations used to understand the function of the biological circuit.
Picture 2: The core transcriptional negative feedback loop and additional negative feedback loop in the biological circuit (picture 1) generate robust rhythms. The snapshots correspond the red dots in the time series graph.
2015.08.31 View 8194 -
'Engineered Bacterium Produces 1,3-Diaminopropane'
A research team led by Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering at KAIST reported, for the first time, the production of 1,3-diaminopropane via fermentation of an engineered bacterium.
1,3-Diaminopropane is a three carbon diamine, which has a wide range of industrial applications including epoxy resin and cross-linking agents, as well as precursors for pharmaceuticals, agrochemicals, and organic chemicals. It can also be polymerized with dicarboxylic acids to make polyamides (nylons) for use as engineering plastics, medical materials, and adhesives.
Traditionally, 1,3-diaminopropane is derived from petroleum-based processes. In effort to address critical problems such as the depletion of petroleum and environmental issues inherent to the petroleum-based processes, the research team has developed an Escherichia coli (E. coli) strain capable of producing 1,3-diaminopropane. Using this technology, 1,3-diaminopropane can now be produced from renewable biomass instead of petroleum.
E. coli as found in nature is unable to produce 1,3-diaminopropane. Metabolic engineering, a technology to transform microorganisms into highly efficient microbial cell factories capable of producing chemical compounds of interest, was utilized to engineer the E. coli strain. First, naturally existing metabolic pathways for the biosynthesis of 1,3-diaminopropane were introduced into a virtual cell in silico to determine the most efficient metabolic pathway for the 1,3-diaminopropane production. The metabolic pathway selected was then introduced into an E. coli strain and successfully produced 1,3-diaminopropane for the first time in the world.
The research team applied metabolic engineering additionally, and the production titer of 1,3-diaminopropane increased about 21 fold. The Fed-batch fermentation of the engineered E. coli strain produced 13 grams per liter of 1,3-diaminoproapne. With this technology, 1,3-diaminopropane can be produced using renewable biomass, and it will be the starting point for replacing the current petroleum-based processes with bio-based processes.
Professor Lee said, “Our study suggested a possibility to produce 1,3-diaminopropane based on biorefinery. Further study will be done to increase the titer and productivity of 1,3-diaminopropane.”
This work was published online in Scientific Reports on August 11, 2015.
Reference: Chae, T.U. et al. "Metabolic engineering of Escherichia coli for the production of 1,3-diaminopropane, a three carbon diamine," Scientific Reports:
http://www.nature.com/articles/srep13040
This research was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea.
Figure 1: Metabolic engineering strategies for 1,3-diaminopropane production using C4 pathway
Figure 2: Fed-batch fermentation profiles of two final engineered E. coli strains
2015.08.12 View 10104 -
KAIST Develops Fiber-Like Light-Emitting Diodes for Wearable Displays
Professor Kyung-Cheol Choi and his research team from the School of Electrical Engineering at KAIST have developed fiber-like light-emitting diodes (LEDs), which can be applied in wearable displays. The research findings were published online in the July 14th issue of Advanced Electronic Materials.
Traditional wearable displays were manufactured on a hard substrate, which was later attached to the surface of clothes. This technique had limited applications for wearable displays because they were inflexible and ignored the characteristics of fabric.
To solve this problem, the research team discarded the notion of creating light-emitting diode displays on a plane. Instead, they focused on fibers, a component of fabrics, and developed a fiber-like LED that shared the characteristics of both fabrics and displays.
The essence of this technology, the dip-coating process, is to immerse and extract a three dimensional (3-D) rod (a polyethylene terephthalate fiber) from a solution, which functions like thread. Then, the regular levels of organic materials are formed as layers on the thread.
The dip-coating process allows the layers of organic materials to be easily created on the fibers with a 3-D cylindrical structure, which had been difficult in existing processes such as heat-coating process. By controlling of the withdrawal rate of the fiber, the coating's thickness can also be adjusted to the hundreds of thousandths of a nanometer.
The researchers said that this technology would accelerate the commercialization of fiber-based wearable displays because it offers low-cost mass production using roll-to-roll processing, a technology applied to create electronic devices on a roll of flexible plastics or metal foils.
Professor Choi said, “Our research will become a core technology in developing light emitting diodes on fibers, which are fundamental elements of fabrics. We hope we can lower the barrier of wearable displays entering the market.”
The lead author of the published paper, Seon-Il Kwon, added, “This technology will eventually allow the production of wearable displays to be as easy as making clothes.”
Picture 1: The Next Generation Wearable Display Using Fiber-Based Light-Emitting Diodes
Picture 2: Dip-Coating Process to Create Fiber-Based Light-Emitting Diodes
Picture 3: Fiber-Based Light-Emitting Diodes
2015.08.11 View 12559