Chemical+and+Biomolecular+Engineering
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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 8875 -
Researchers Control Multiple Wavelengths of Light from a Single Source
KAIST researchers have synthesized a collection of nanoparticles, known as carbon dots, capable of emitting multiple wavelengths of light from a single particle. Additionally, the team discovered that the dispersion of the carbon dots, or the interparticle distance between each dot, influences the properties of the light the carbon dots emit. The discovery will allow researchers to understand how to control these carbon dots and create new, environmentally responsible displays, lighting, and sensing technology.
Research into nanoparticles capable of emitting light, such as quantum dots, has been an active area of interest for the last decade and a half. These particles, or phosphors, are nanoparticles made out of various materials that are capable of emitting light at specific wavelengths by leveraging quantum mechanical properties of the materials. This provides new ways to develop lighting and display solutions as well as more precise detection and sensing in instruments.
As technology becomes smaller and more sophisticated, the usage of fluorescent nanoparticles has seen a dramatic increase in many applications due to the purity of the colors emitting from the dots as well as their tunability to meet desired optical properties.
Carbon dots, a type of fluorescent nanoparticles, have seen an increase in interest from researchers as a candidate to replace non-carbon dots, the construction of which requires heavy metals that are toxic to the environment. Since they are made up of mostly carbon, the low toxicity is an extremely attractive quality when coupled with the tunability of their inherent optical properties.
Another striking feature of carbon dots is their capability to emit multiple wavelengths of light from a single nanoparticle. This multi-wavelength emission can be stimulated under a single excitation source, enabling the simple and robust generation of white light from a single particle by emitting multiple wavelengths simultaneously.
Carbon dots also exhibit a concentration-dependent photoluminescence. In other words, the distance between individual carbon dots affects the light that the carbon dots subsequently emit under an excitation source. These combined properties make carbon dots a unique source that will result in extremely accurate detection and sensing.
This concentration-dependency, however, had not been fully understood. In order to fully utilize the capabilities of carbon dots, the mechanisms that govern the seemingly variable optical properties must first be uncovered. It was previously theorized that the concentration-dependency of carbon dots was due to a hydrogen bonding effect.
Now, a KAIST research team, led by Professor Do Hyun Kim of the Department of Chemical and Biomolecular Engineering has posited and demonstrated that the dual-color-emissiveness is instead due to the interparticle distances between each carbon dot. This study was made available online in June 2020 ahead of final publication in the 36th Issue of Physical Chemistry Chemical Physics on September 28, 2020.
First author of the paper, PhD candidate Hyo Jeong Yoo, along with Professor Kim and researcher Byeong Eun Kwak, examined how the relative light intensity of the red and blue colors changed when varying the interparticle distances, or concentration, of the carbon dots. They found that as the concentration was adjusted, the light emitted from the carbon dots would transform. By varying the concentration, the team was able to control the relative intensity of the colors, as well as emit them simultaneously to generate a white light from a single source (See Figure).
“The concentration-dependence of the photoluminescence of carbon dots on the change of the emissive origins for different interparticle distances has been overlooked in previous research. With the analysis of the dual-color-emission phenomenon of carbon dots, we believe that this result may provide a new perspective to investigate their photoluminescence mechanism,” Yoo explained.
The newly analyzed ability to control the photoluminescence of carbon dots will likely be heavily utilized in the continued development of solid-state lighting applications and sensing.
Publication:
Yoo, H. J., Kwak, B. E., and Kim. D. H. (2020) Interparticle distance as a key factor for controlling the dual-emission properties of carbon dots. Physical Chemistry Chemical Physics, Issue 36, Pages 20227-20237. Available online at https://doi.org/10.1039/d0cp02120b
Profile:
Do Hyun Kim, Sc.D.
Professor
dokim@kaist.ac.kr
http://procal.kaist.ac.kr/
Process Analysis Laboratory
Department of Chemical and Biomolecular Engineering
https://www.kaist.ac.kr
Korea Advanced Institute of Science and Technology (KAIST)Daejeon, Republic of Korea
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2020.11.23 View 9232 -
Engineered C. glutamicum Strain Capable of Producing High-Level Glutaric Acid from Glucose
An engineered C. glutamicum strain that can produce the world’s highest titer of glutaric acid was developed by employing systems metabolic engineering strategies
A metabolic engineering research group at KAIST has developed an engineered Corynebacterium glutamicum strain capable of producing high-level glutaric acid without byproducts from glucose. This new strategy will be useful for developing engineered micro-organisms for the bio-based production of value-added chemicals.
Glutaric acid, also known as pentanedioic acid, is a carboxylic acid that is widely used for various applications including the production of polyesters, polyamides, polyurethanes, glutaric anhydride, 1,5-pentanediol, and 5-hydroxyvaleric acid. Glutaric acid has been produced using various petroleum-based chemical methods, relying on non-renewable and toxic starting materials. Thus, various approaches have been taken to biologically produce glutaric acid from renewable resources. Previously, the development of the first glutaric acid producing Escherichia coli by introducing Pseudomonas putida genes was reported by a research group from KAIST, but the titer was low. Glutaric acid production by metabolically engineered Corynebacterium glutamicum has also been reported in several studies, but further improvements in glutaric acid production seemed possible since C. glutamicum has the capability of producing more than 130 g/L of L-lysine.
A research group comprised of Taehee Han, Gi Bae Kim, and Distinguished Professor Sang Yup Lee of the Department of Chemical and Biomolecular Engineering addressed this issue. Their research paper “Glutaric acid production by systems metabolic engineering of an L-lysine-overproducing Corynebacterium glutamicum” was published online in PNAS on November 16, 2020.
This research reports the development of a metabolically engineered C. glutamicum strain capable of efficiently producing glutaric acid, starting from an L-lysine overproducer. The following novel strategies and approaches to achieve high-level glutaric acid production were employed. First, metabolic pathways in C. glutamicum were reconstituted for glutaric acid production by introducing P. putida genes. Then, multi-omics analyses including genome, transcriptome, and fluxome were conducted to understand the phenotype of the L-lysine overproducer strain. In addition to systematic understanding of the host strain, gene manipulation targets were predicted by omics analyses and applied for engineering C. glutamicum, which resulted in the development of an engineered strain capable of efficiently producing glutaric acid. Furthermore, the new glutaric acid exporter was discovered for the first time, which was used to further increase glutaric acid production through enhancing product excretion. Last but not least, culture conditions were optimized for high-level glutaric acid production. As a result, the final engineered strain was able to produce 105.3 g/L glutaric acid, the highest titer ever reported, in 69 hours by fed-batch fermentation.
Professor Sang Yup Lee said, “It is meaningful that we were able to develop a highly efficient glutaric acid producer capable of producing glutaric acid at the world’s highest titer without any byproducts from renewable carbon sources. This will further accelerate the bio-based production of valuable chemicals in pharmaceutical/medical/chemical industries.” This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation and funded by the Ministry of Science and ICT.
-Profile
Distinguished Professor Sang Yup Lee
leesy@kaist.ac.kr
http://mbel.kaist.ac.kr
Department of Chemical and Biomolecular Engineering
KAIST
2020.11.17 View 6195 -
E. coli Engineered to Grow on CO₂ and Formic Acid as Sole Carbon Sources
- An E. coli strain that can grow to a relatively high cell density solely on CO₂ and formic acid was developed by employing metabolic engineering. -
Most biorefinery processes have relied on the use of biomass as a raw material for the production of chemicals and materials. Even though the use of CO₂ as a carbon source in biorefineries is desirable, it has not been possible to make common microbial strains such as E. coli grow on CO₂.
Now, a metabolic engineering research group at KAIST has developed a strategy to grow an E. coli strain to higher cell density solely on CO₂ and formic acid. Formic acid is a one carbon carboxylic acid, and can be easily produced from CO₂ using a variety of methods. Since it is easier to store and transport than CO₂, formic acid can be considered a good liquid-form alternative of CO₂.
With support from the C1 Gas Refinery R&D Center and the Ministry of Science and ICT, a research team led by Distinguished Professor Sang Yup Lee stepped up their work to develop an engineered E. coli strain capable of growing up to 11-fold higher cell density than those previously reported, using CO₂ and formic acid as sole carbon sources. This work was published in Nature Microbiology on September 28.
Despite the recent reports by several research groups on the development of E. coli strains capable of growing on CO₂ and formic acid, the maximum cell growth remained too low (optical density of around 1) and thus the production of chemicals from CO₂ and formic acid has been far from realized.
The team previously reported the reconstruction of the tetrahydrofolate cycle and reverse glycine cleavage pathway to construct an engineered E. coli strain that can sustain growth on CO₂ and formic acid. To further enhance the growth, the research team introduced the previously designed synthetic CO₂ and formic acid assimilation pathway, and two formate dehydrogenases.
Metabolic fluxes were also fine-tuned, the gluconeogenic flux enhanced, and the levels of cytochrome bo3 and bd-I ubiquinol oxidase for ATP generation were optimized. This engineered E. coli strain was able to grow to a relatively high OD600 of 7~11, showing promise as a platform strain growing solely on CO₂ and formic acid.
Professor Lee said, “We engineered E. coli that can grow to a higher cell density only using CO₂ and formic acid. We think that this is an important step forward, but this is not the end. The engineered strain we developed still needs further engineering so that it can grow faster to a much higher density.”
Professor Lee’s team is continuing to develop such a strain. “In the future, we would be delighted to see the production of chemicals from an engineered E. coli strain using CO₂ and formic acid as sole carbon sources,” he added.
-Profile:Distinguished Professor Sang Yup Leehttp://mbel.kaist.ac.krDepartment of Chemical and Biomolecular EngineeringKAIST
2020.09.29 View 9502 -
Sulfur-Containing Polymer Generates High Refractive Index and Transparency
Transparent polymer thin film with refractive index exceeding 1.9 to serve as new platform materials for high-end optical device applications
Researchers reported a novel technology enhancing the high transparency of refractive polymer film via a one-step vapor deposition process. The sulfur-containing polymer (SCP) film produced by Professor Sung Gap Im’s research team at KAIST’s Department of Chemical and Biomolecular Engineering has exhibited excellent environmental stability and chemical resistance, which is highly desirable for its application in long-term optical device applications. The high refractive index exceeding 1.9 while being fully transparent in the entire visible range will help expand the applications of optoelectronic devices.
The refractive index is a ratio of the speed of light in a vacuum to the phase velocity of light in a material, used as a measure of how much the path of light is bent when passing through a material. With the miniaturization of various optical parts used in mobile devices and imaging, demand has been rapidly growing for high refractive index transparent materials that induce more light refraction with a thin film.
As polymers have outstanding physical properties and can be easily processed in various forms, they are widely used in a variety of applications such as plastic eyeglass lenses. However, there have been very few polymers developed so far with a refractive index exceeding 1.75, and existing high refractive index polymers require costly materials and complicated manufacturing processes.
Above all, core technologies for producing such materials have been dominated by Japanese companies, causing long-standing challenges for Korean manufacturers. Securing a stable supply of high-performance, high refractive index materials is crucial for the production of optical devices that are lighter, more affordable, and can be freely manipulated.
The research team successfully manufactured a whole new polymer thin film material with a refractive index exceeding 1.9 and excellent transparency, using just a one-step chemical reaction. The SCP film showed outstanding optical transparency across the entire visible light region, presumably due to the uniformly dispersed, short-segment polysulfide chains, which is a distinct feature unachievable in polymerizations with molten sulfur.
The team focused on the fact that elemental sulfur is easily sublimated to produce a high refractive index polymer by polymerizing the vaporized sulfur with a variety of substances. This method suppresses the formation of overly long S-S chains while achieving outstanding thermal stability in high sulfur concentrations and generating transparent non-crystalline polymers across the entire visible spectrum.
Due to the characteristics of the vapor phase process, the high refractive index thin film can be coated not just on silicon wafers or glass substrates, but on a wide range of textured surfaces as well. We believe this thin film polymer is the first to have achieved an ultrahigh refractive index exceeding 1.9.
Professor Im said, “This high-performance polymer film can be created in a simple one-step manner, which is highly advantageous in the synthesis of SCPs with a high refractive index. This will serve as a platform material for future high-end optical device applications.”
This study, in collaboration with research teams from Seoul National University and Kyung Hee University, was reported in Science Advances. (Title: One-Step Vapor-Phase Synthesis of Transparent High-Refractive Index Sulfur-Containing Polymers）
This research was supported by the Ministry of Science and ICT’s Global Frontier Project (Center for Advanced Soft-Electronics), Leading Research Center Support Program (Wearable Platform Materials Technology Center), and Basic Science Research Program (Advanced Research Project).
2020.08.04 View 8086 -
A New Strategy for Early Evaluations of CO2 Utilization Technologies
- A three-step evaluation procedure based on technology readiness levels helps find the most efficient technology before allocating R&D manpower and investments in CO2 utilization technologies. -
Researchers presented a unified framework for early-stage evaluations of a variety of emerging CO2 utilization (CU) technologies. The three-step procedure allows a large number of potential CU technologies to be screened in order to identify the most promising ones, including those at low level of technical maturity, before allocating R&D manpower and investments.
When evaluating new technology, various aspects of the new technology should be considered. Its feasibility, efficiency, economic competitiveness, and environmental friendliness are crucial, and its level of technical maturity is also an important component for further consideration. However, most technology evaluation procedures are data-driven, and the amount of reliable data in the early stages of technology development has been often limited.
A research team led by Professor Jay Hyung Lee from the Department of Chemical and Biomolecular Engineering at KAIST proposed a new procedure for evaluating the early development stages of emerging CU technologies which are applicable at various technology readiness levels (TRLs).
The procedure obtains performance indicators via primary data preparation, secondary data calculation, and performance indicator calculation, and the lead author of the study Dr. Kosan Roh and his colleagues presented a number of databases, methods, and computer-aided tools that can effectively facilitate the procedure.
The research team demonstrated the procedure through four case studies involving novel CU technologies of different types and at various TRLs. They confirmed the electrochemical CO2 reduction for the production of ten chemicals, the co-electrolysis of CO2 and water for ethylene production, the direct oxidation of CO2 -based methanol for oxymethylene dimethyl production, and the microalgal biomass co-firing for power generation.
The expected range of the performance indicators for low TRL technologies is broader than that for high TRL technologies, however, it is not the case for high TRL technologies as they are already at an optimized state. The research team believes that low TRL technologies will be significantly improved through future R&D until they are commercialized. “We plan to develop a systematic approach for such a comparison to help avoid misguided decision-making,” Professor Lee explained.
Professor Lee added, “This procedure allows us to conduct a comprehensive and systematic evaluation of new technology. On top of that, it helps make efficient and reliable assessment possible.”
The research team collaborated with Professor Alexander Mitsos, Professor André Bardow, and Professor Matthias Wessling at RWTH Aachen University in Germany. Their findings were reported in Green Chemistry on May 21. This work was supported by the Korea Carbon Capture and Sequestration R&D Center (KCRC).
Publications:
Roh, K., et al. (2020) ‘Early-stage evaluation of emerging CO2 utilization technologies at low technology readiness levels’ Green Chemistry. Available online at https://doi.org/10.1039/c9gc04440j
Profile: Jay Hyung Lee, Ph.D.
Professor
jayhlee@kaist.ac.kr
http://lense.kaist.ac.kr/
Laboratory for Energy System Engineering (LENSE)
Department of Chemical and Biomolecular Engineering
KAIST
https://www.kaist.ac.kr
Daejeon 34141, Korea
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2020.06.22 View 8893 -
Universal Virus Detection Platform to Expedite Viral Diagnosis
Reactive polymer-based tester pre-screens dsRNAs of a wide range of viruses without their genome sequences
The prompt, precise, and massive detection of a virus is the key to combat infectious diseases such as Covid-19. A new viral diagnostic strategy using reactive polymer-grafted, double-stranded RNAs will serve as a pre-screening tester for a wide range of viruses with enhanced sensitivity.
Currently, the most widely using viral detection methodology is polymerase chain reaction (PCR) diagnosis, which amplifies and detects a piece of the viral genome. Prior knowledge of the relevant primer nucleic acids of the virus is quintessential for this test.
The detection platform developed by KAIST researchers identifies viral activities without amplifying specific nucleic acid targets. The research team, co-led by Professor Sheng Li and Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering, constructed a universal virus detection platform by utilizing the distinct features of the PPFPA-grafted surface and double-stranded RNAs.
The key principle of this platform is utilizing the distinct feature of reactive polymer-grafted surfaces, which serve as a versatile platform for the immobilization of functional molecules. These activated surfaces can be used in a wide range of applications including separation, delivery, and detection. As long double-stranded RNAs are common byproducts of viral transcription and replication, these PPFPA-grafted surfaces can detect the presence of different kinds of viruses without prior knowledge of their genomic sequences.
“We employed the PPFPA-grafted silicon surface to develop a universal virus detection platform by immobilizing antibodies that recognize double-stranded RNAs,” said Professor Kim.
To increase detection sensitivity, the research team devised two-step detection process analogues to sandwich enzyme-linked immunosorbent assay where the bound double-stranded RNAs are then visualized using fluorophore-tagged antibodies that also recognize the RNAs’ double-stranded secondary structure.
By utilizing the developed platform, long double-stranded RNAs can be detected and visualized from an RNA mixture as well as from total cell lysates, which contain a mixture of various abundant contaminants such as DNAs and proteins.
The research team successfully detected elevated levels of hepatitis C and A viruses with this tool.
“This new technology allows us to take on virus detection from a new perspective. By targeting a common biomarker, viral double-stranded RNAs, we can develop a pre-screening platform that can quickly differentiate infected populations from non-infected ones,” said Professor Li.
“This detection platform provides new perspectives for diagnosing infectious diseases. This will provide fast and accurate diagnoses for an infected population and prevent the influx of massive outbreaks,” said Professor Kim.
This work is featured in Biomacromolecules. This work was supported by the Agency for Defense Development (Grant UD170039ID), the Ministry of Science and ICT (NRF-2017R1D1A1B03034660, NRF-2019R1C1C1006672), and the KAIST Future Systems Healthcare Project from the Ministry of Science and ICT (KAISTHEALTHCARE42).
Profile:-Professor Yoosik KimDepartment of Chemical and Biomolecular Engineeringhttps://qcbio.kaist.ac.kr
KAIST-Professor Sheng LiDepartment of Chemical and Biomolecular Engineeringhttps://bcpolymer.kaist.ac.kr
KAIST
Publication:Ku et al., 2020. Reactive Polymer Targeting dsRNA as Universal Virus Detection Platform with Enhanced Sensitivity. Biomacromolecules (https://doi.org/10.1021/acs.biomac.0c00379).
2020.06.01 View 17084 -
The 10th KINC Fusion Research Awardees
The KAIST Institute for NanoCentury (KINC) recognized three distinguished researchers whose convergence studies made significant impacts. The KINC presented the 10th KINC Fusion Research Awards during a ceremony that took place at KAIST’s main campus in Daejeon on May 19.
This year’s ‘best’ convergence research award went to a joint research group led by Professor Hee Tak Kim from the Department of Chemical and Biomolecular Engineering and Professor Sang Ouk Kim from the Department of Materials Science and Engineering. Their research, featured in the December 27 issue of Advanced Materials as a front cover article last year, introduced the world’s first high-energy efficiency, membraneless, flowless, zinc-bromine battery. This study, in which research professor Gyoung Hwa Jeong, postdoctoral researcher Yearin Byun, and PhD candidate Ju-Hyuck Lee took part as co-lead authors, is deemed as an example of a best practice in convergence research in which two groups’ respective expertise in the fields of carbon materials and electrochemical analysis created a synergistic effect.
Professor Bumjoon Kim from the Department of Chemical and Biomolecular Engineering was also recognized for having published the most interdisciplinary research papers on polymer electronics and nanomaterials at home and abroad.
Professor Hee-Tae Jung, the Director of KINC and the host of the KINC Fusion Research Awards, said, “The KINC is happy to announce the 10th awardees in nano-fusion research this year. Since convergence is crucial for making revolutionary changes, the importance of convergence studies should be recognized. Our institute will spare no effort to create a research environment suitable for convergence studies, which will be crucial for making a significant difference.”
The KINC was established in June 2006 under the KAIST Institute with the mission of facilitating convergence studies by tearing down boarders among departments and carrying out interdisciplinary joint research. Currently, the institute is comprised of approximately 90 professors from 13 departments. It aims to become a hub of university institutes for nano-fusion research.
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2020.05.19 View 11740 -
What Fuels a “Domino Effect” in Cancer Drug Resistance?
KAIST researchers have identified mechanisms that relay prior acquired resistance to the first-line chemotherapy to the second-line targeted therapy, fueling a “domino effect” in cancer drug resistance. Their study featured in the February 7 edition of Science Advances suggests a new strategy for improving the second-line setting of cancer treatment for patients who showed resistance to anti-cancer drugs.
Resistance to cancer drugs is often managed in the clinic by chemotherapy and targeted therapy. Unlike chemotherapy that works by repressing fast-proliferating cells, targeted therapy blocks a single oncogenic pathway to halt tumor growth. In many cases, targeted therapy is engaged as a maintenance therapy or employed in the second-line after front-line chemotherapy.
A team of researchers led by Professor Yoosik Kim from the Department of Chemical and Biomolecular Engineering and the KAIST Institute for Health Science and Technology (KIHST) has discovered an unexpected resistance signature that occurs between chemotherapy and targeted therapy. The team further identified a set of integrated mechanisms that promotes this kind of sequential therapy resistance.
“There have been multiple clinical accounts reflecting that targeted therapies tend to be least successful in patients who have exhausted all standard treatments,” said the first author of the paper Mark Borris D. Aldonza. He continued, “These accounts ignited our hypothesis that failed responses to some chemotherapies might speed up the evolution of resistance to other drugs, particularly those with specific targets.”
Aldonza and his colleagues extracted large amounts of drug-resistance information from the open-source database the Genomics of Drug Sensitivity in Cancer (GDSC), which contains thousands of drug response data entries from various human cancer cell lines. Their big data analysis revealed that cancer cell lines resistant to chemotherapies classified as anti-mitotic drugs (AMDs), toxins that inhibit overacting cell division, are also resistant to a class of targeted therapies called epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).
In all of the cancer types analyzed, more than 84 percent of those resistant to AMDs, representatively ‘paclitaxel’, were also resistant to at least nine EGFR-TKIs. In lung, pancreatic, and breast cancers where paclitaxel is often used as a first-line, standard-of-care regimen, greater than 92 percent showed resistance to EGFR-TKIs. Professor Kim said, “It is surprising to see that such collateral resistance can occur specifically between two chemically different classes of drugs.”
To figure out how failed responses to paclitaxel leads to resistance to EGFR-TKIs, the team validated co-resistance signatures that they found in the database by generating and analyzing a subset of slow-doubling, paclitaxel-resistant cancer models called ‘persisters’.
The results demonstrated that paclitaxel-resistant cancers remodel their stress response by first becoming more stem cell-like, evolving the ability to self-renew to adapt to more stressful conditions like drug exposures. More surprisingly, when the researchers characterized the metabolic state of the cells, EGFR-TKI persisters derived from paclitaxel-resistant cancer cells showed high dependencies to energy-producing processes such as glycolysis and glutaminolysis.
“We found that, without an energy stimulus like glucose, these cells transform to becoming more senescent, a characteristic of cells that have arrested cell division. However, this senescence is controlled by stem cell factors, which the paclitaxel-resistant cancers use to escape from this arrested state given a favorable condition to re-grow,” said Aldonza.
Professor Kim explained, “Before this research, there was no reason to expect that acquiring the cancer stem cell phenotype that dramatically leads to a cascade of changes in cellular states affecting metabolism and cell death is linked with drug-specific sequential resistance between two classes of therapies.”
He added, “The expansion of our work to other working models of drug resistance in a much more clinically-relevant setting, perhaps in clinical trials, will take on increasing importance, as sequential treatment strategies will continue to be adapted to various forms of anti-cancer therapy regimens.”
This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2016R1C1B2009886), and the KAIST Future Systems Healthcare Project (KAISTHEALTHCARE42) funded by the Korean Ministry of Science and ICT (MSIT). Undergraduate student Aldonza participated in this research project and presented the findings as the lead author as part of the Undergraduate Research Participation (URP) Program at KAIST.
< Figure 1. Schematic overview of the study. >
< Figure 2. Big data analysis revealing co-resistance signatures between classes of anti-cancer drugs. >
Publication:
Aldonza et al. (2020) Prior acquired resistance to paclitaxel relays diverse EGFR-targeted therapy persistence mechanisms. Science Advances, Vol. 6, No. 6, eaav7416. Available online at http://dx.doi.org/10.1126/sciadv.aav7416
Profile: Prof. Yoosik Kim, MA, PhD
ysyoosik@kaist.ac.kr
https://qcbio.kaist.ac.kr/
Assistant Professor
Bio Network Analysis Laboratory
Department of Chemical and Biomolecular Engineering
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
Profile: Mark Borris D. Aldonza
borris@kaist.ac.kr
Undergraduate Student
Department of Biological Sciences
Korea Advanced Institute of Science and Technology (KAIST)
http://kaist.ac.kr
Daejeon, Republic of Korea
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2020.02.10 View 11599 -
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.”
(END)
2019.12.21 View 6511 -
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 18754 -
Professor Hyun Gyu Park Appointed as Associate Editor for Biosensors and Bioelectronics
Professor Hyun Gyu Park from the Department of Chemical and Biomolecular Engineering was appointed as an associate editor for Biosensors and Bioelectronics, an international journal published by Elsevier.
Biosensors and Bioelectronics is one of the top SCI journals in the fields of chemistry and analytical science (IF 9.518 as of 2018). Professor Park was recognized and appointed as the associate editor for this journal due to his outstanding research achievements in the fields of nucleic acid engineering, biosensors, and nanobiotechnology.
Professor Park will serve as the associate editor from this October until December 2021.
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2019.10.01 View 5765