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RESEARCH 
Research Highlights |
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 Professor Hyung Joon Cha
Practical recombinant mussel bioadhesive |
Professor Hyung Joon Cha and his team at the Department of Chemical Engineering have developed a novel type of practical recombinant hybrid bioadhesive material that is originated from marine mussel. And it is now in commercialization stage as cell and tissue bioadhesive (first item) under collaboration with Kollodis Biosciences.
Mussels produce and secrete specialized adhesives that work in water allowing them to attach themselves in rough marine environments. The mussel adhesive proteins (MAPs) adhere tightly to substrata using the byssus secreted from the foot, which is composed of a bundle of threads. At the end of each thread, there is an adhesion plaque containing a water-resistant adhesive that enables the plaque to anchor to wet, solid surface. This adhesion plaque is composed of five distinct types of protein ? foot proteins type 1 (fp-1) to type 5 (fp-5). These strong, water-insoluble, and environmentally friendly mussel adhesives can be used as cell, tissue, or medical adhesives.
Professor Cha and his team designed and produced the novel type of hybrid MAP fp-151, which is a fusion protein comprising six fp-1 decapeptide repeats added to the N- and C-termini of fp-5 in E. coli cells. Using micro- and bulk-scale characterization and mammalian/human cell-adhesionanalyses, they demonstrated that hybrid fp-151 has the potential to be a practical bioadhesive with strong adhesive ability (~10 kg subject can be attached on 1 cm2 area using 40 mg hybrid fp-151), a simple purification process (~1 g-purified protein per 1 liter-pilot-scale fed-batch bioreactor culture), proper manipulation properties (~300 g/l solubility), and high biocompatibility.
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Professor Kimoon Kim
A synthetic host-guest system achieves avidin-biotin affinity |
Prof. Kimoon Kim and colleagues at the Department of Chemistry have developed a synthetic host-guest system with an ultrahigh stability similar to that of the avidin-biotin complex. The molecular host cucurbit[7]uril (CB[7]) forms an extremely stable inclusion complex with the dicationic ferrocene derivative (K = 3 1015 M?1), which achieves its extreme affinity by overcoming the compensatory enthalpy-entropy relationship usually observed in supramolecular complexes. The new high-affinity host-guest pair could serve as an extremely strong but redox-active reversible fastener in self-assembling chemical and biological supramolecular systems.
The avidin-biotin system widely used in many applications such as immunological assays suffers some shortcomings including denaturation by organic solvents or elevated temperatures, large size and high cost. The synthetic host-guest pair with exceptional affinity, chemical robustness, simple preparation, andeasy handling may thus replace the biotin-avidin system not only in the immobilization of biomolecules on solid surfaces, but also in other applications such as affinity chromatography and immunoassay. For example, Prof. Kim recently reported a novel noncovalent method to immobilize a protein on a solid surface using the CB[7]?ferrocenemethylammonium pair.
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X-ray crystal structure of cucurbit[7]uril-ferrocene derivative complex.
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Professor Joon Won Park
NanoCone Technology |
A cone-shaped dendron called NanoCone has a well-defined three-dimensional structure and its size can be changed precisely. When this monodisperse molecule is coated on a surface, branches of the NanoCone form stable chemical bonds with the surface of a substrate, and a functional group at its apex is utilized for immobilization of a bioactive molecule. In addition, these molecules are located on the surface having the regular lateral spacing between them which was directly observed by using a high resolution scanning electron microscope (HRSEM). The average spacing was 3.2 ± 0.4 nm and density 0.05 - 0.06 ea/nm2. Also, in all of the cases, the spacing was larger than 2 nm. Topographical images obtained by atomic force microscopy (AFM) also showed that the resulting layer was smooth and homogeneous without any aggregates or holes in macroscopic scale.
Therefore, the particular topological structure of the employed NanoCone surface allows the optimal spacing between biomolecules on the surface for diagnosis or bioassay. By choosing appropriate size and degree of branching of the NSB, the spacing can be precisely controlled from 3 up to more than10 nanometers. Also, a stringent choice of chemical structure of its backbone and organic sublayer effectively suppresses undesirable nonspecific binding of various biomolecules.
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SEM image of NSB surface and different sizes of NanoCones
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Professor Kyong Tai Kim
To Sleep, Perchance to Dream: New Insight into Melatonin Production |
Melatonin is a hormone produced by the pineal gland in the brain, which helps to regulate our bodies' circadian rhythm. The rhythmicity of pineal melatonin requires the nocturnal increment of AANAT protein which is a key enzyme in the melatonin biosynthesis pathway. To date, only limited information is available in the critical issue of how AANAT protein expression is up-regulated exclusively at night. We show that the circadian timing of AANAT protein expression is regulated by rhythmic translation of AANAT mRNA. This rhythmic control is mediated by both a highly conserved IRES element within the AANAT 5' UTR and its partner hnRNP Q with a peak in the middle of the night. Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of hnRNP Q level elicited a dramatic decrease of peak amplitude in AANAT protein profile parallel to reduced melatonin production in pinealocytes. This translational mechanism is a novel aspect for framing the circadian rhythmicity of vertebrate melatonin, and provides possible cues to develop the therapeutic drugs for sleep disorder-related diseases. (Genes and Development ,2007 )
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Professor Young-Chul Sung
A therapeutic DNA vaccine against chronic hepatitis B |
A therapeutic DNA vaccine against chronic hepatitis B A defective hepatitis B virus (HBV)-specific T-cell response was observed in chronic hepatitis B carriers and considered to be a major determinant of viral persistence. Therefore, an effective immunotherapeutic approach should be capable of generating strong and long-lasting HBV-specific T cell responses. In this study, 12 Caucasian HBV carriers were intramuscularly injected 12 times with HBV DNA vaccine (HB-100) at 4-week intervals in combination with 100 mg of LAM (Epivir-HBV, GlaxoSmithKline) daily for 52 ± 4 weeks and then followed up for another 52 weeks. HBV DNA vaccine contains multiple genes encoding HBV antigens and a genetically engineered human IL-12 mutant as a genetic adjuvant to induce broad and strong immune responses. To evaluate the HBV antigen-specific T cell responses, we performed an ex vivo and cultured IFN-g ELISPOT assay. We observed the restoration of anti-HBV T cel responses by treatment with LAM + HB-100. The observed T cell responses, particularly memory T cell responses could be maintained for at least 40 weeks after the combined therapy and correlated with virological responses, but not with alanine aminotransferase (ALT) elevation. Moreover, DNA vaccination under lamivudine (LAM) treatment appeared to be well-tolerated and showed 50% of virological response rate in CHB carriers. Taken together, combination therapy of the DNA vaccine with chemotherapy may be one of new immunotherapeutic methods for the cure of CHB. (Gene Therapy ,2007)
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Professor Pann-Ghill Suh
A "biologicla switch" that controls the cell growth
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Professor Pann-Ghill Suh and Dr. Jang Hyun Choi have recently discovered a "biological switch" that controls the growth and development of the cells, and their work was introduced on the internet of Nature Cell Biology on November 27, 2006. According to their study, the phospolypaseC-g1 (PLC-g1), an intracellular enzyme, acts to suppress the signal transduction of growth factor hormone secreted in the brain when it is in combination with 'PTP-1B'. According to the experiment, the PLC-g1 intermediating the cell growth did not properly induce signal transduction when in combination with 'PTP-1B.' Although there have been numerous studies on the effects of growth factor hormones on cell growth and differentiation, the specific signal pathways involved in this process have been unknown. Therefore, the result of their study will help to treat metabolic diseases including diabetics and cancers caused by over secretion of hormones. Professor Suh and his group has been conducting research regarding phospholipase C-mediated signal transduction and physiological function of PLC using PLC Knock-Out and Knock-In mice. (Nature Cell Biology Internet,2006) ▲TOP |
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Professor Sung Ho Ryu
Mechanism of intercellular or intracellular communication in multicellular organisms
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Cancer and diabetes, which are one of the most typical diseases in adults, are associated with inter or intra-cellular miscommunication, which are related to abnormal stimulation of membrane receptors. In cancer, cells proliferate infinitely by inadequate stimulation of Epidermal Growth Factor (EGF) itself or its receptor. In Type-II diabetes, blood glucose level cannot be controlled because adipose or muscle cells cannot properly respond to insulin even though insulin itself is present.Professor Sung Ho Ryu’s team has revealed that phospholipase D (PLD) acts as "a timer" which regulates the length of the time of EGF or insulin’s action on their receptors. Therefore, Ryu’s team illustrated how the newly discovered timer protein (PLD)regulates dynamin, an endocytosis machinery, at molecular level, and identified the role of PLD as a timer to determine when to use this molecular scissor (Nature Cell Biology, 2006, 5, 477-484). The research, which discovered timer for regulating the time of receptor’s stimulation, could be applied in developing target for next-paradigm therapeutics by investigating abnormality of this timer in diseased state.This success led to a new breakthrough in understanding molecular mechanism of regulation of hormonal (signal) stimulus time, which is a core issue in cell-to-cell communication.(Nature Cell Biology,2006,477-484,). ▲TOP |
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Professor Byung-Ha Oh
The architecture of the multisubunit TRAPP I complex suggests a novel model for vesicle tethering |
Transport protein particle (TRAPP) I is a multisubunit vesicle tethering factor composed of seven subunits involved in endoplasmic reticulum-to-Golgi trafficking. The functional mechanism of the complex and how the subunits interact to form a functional unit are unknown. Using a multidisciplinary approach that included X-ray crystallography, electron microscopy, biochemistry and yeast genetics the architecture of TRAPP I was elucidated. This study revealed that mammalian TRAPP I is composed of the bet3-trs33-bet5-trs23 heterotetramer and the bet3-trs31-sedlin heterotrimer as the two stable subcomplexes, while the yeast orthologs of these proteins form a functional and stable six-subunit complex. The crystal structures of the two mammalian subcomplexes were solved and the electron microscopic image reconstruction reavealed that the yeast complex is organized through lateral juxtaposition of the six subunits into a flat and elongated particle. Also localized was the site of guanine nucleotide exchange activity to a highly conserved surface encompassing several subunits. Based on the complete architecture of TRAPP I, we proposed that the complex attaches to Golgi membrane with its large flat surface containing many highly conserved residues and forms a platform for protein-protein interactions that will include Rab1-GTP and possibly long coiled-coil tethers. This study provides the most comprehensive view of a multisubunit vesicle tethering complex to date. (Cell ,2006) ▲TOP |
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Professor Inhwan Hwang
Activation of Glucosidase via Stress-Induced Polymerization Rapidly Increases Active Polls of Abscisic Acid |
Professor Inhwan Hwang and Dr. Kwang Hee Lee of his research team have elucidated a new mechanism involved in the activation of Abscisic Acid (ABA), a phytohormone critical for plant growth, development, and adaptation to various stress conditions such as draught. Their work was published in Cell on September 22, 2006, the most prestigious journal of biology ("Activation of Glucosidase via Stress-Induced Polymerization Rapidly Increases Active Pools of Abscisic Acid" (Cell. 126:1109-1120)). This work is expected to be applied to the cultivation of plants that can grow even in desserts. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. A recent study by Professor Inhwan Hwang and Dr. Kwang Hee Lee of his research team at POSTECH reports that AtBG1, a β-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and display enhanced tolerance to abiotic stress. Dehydration rapidly induces polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity. Furthermore, diurnal increases in ABA levels are attributable to polymerization-mediated AtBG1 activation. They propose that the activation of inactive ABA pools by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and respond to changing environmental cues. (Cell ,2006) ▲TOP |
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Professor Hong Gil Nam
Biochemical iris diaphragm for the control of light information flux in plant |
Biochemical iris diaphragm for the control of light information flux in plantPlants see the light through photoreceptor such as phytochromes, adjusting their growth in various ways from germination to flowering. Light signal information perceived by phytochromes should go through proper biological pathways but, at the same time, the amount of light information flow through the pathways should be controlled for proper biological responses. Prof. Nam’s group revealed how plants regulate the amount of light information flow. They propose a model in which the counter-action of the pair of phytochrome autophosphorylation/phytochrome-associated kinase(s) activity and Pfr form-specific phosphatase activity of PAPP5 provides a tuning mechanism that finely controls the flux of light information to downstream photoresponses. This control is mediated through regulation of phytochrome stability and affinity for downstream signal transducers; the more stable binding, the more signal flow! It is like taking a good photograph. When we take a photograph, we direct the camera lens towards an object but we also need to adjust the shutter speed or the sensitivity of iris diaphragm for a better photograph according to the light environment. (Cell ,2005)
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Profess Yunje Cho
Structural basis for inhibition of the replication licensing factor Cdt1by geminin |
To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2-7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Professor Yunje Cho's team described the crystal structure of the mouse geminin-Cdt1 complex using tGeminin (residues 79-157, truncated geminin) and tCdt1 (residues 172-368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186, AND Leu 189. The crystal structure, in conjunction with the biochemical data that they have, indicates that the N-terminal region of tGeminin ight be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 steric hindrance. (Nature ,2004) ▲TOP |
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Professor Youngsook Lee
Engineering tolerance and accumulation of lead and cadmium in transgenic plants |
Professor Youngsook Lee and her group developed several groups of plants that are improved in tolerance to heavy metals. One group of the plants transformed to express vacuolar sequestering protein are also improved in absorption of lead and cadmium from the environment, which makes them ideal for cleaning up heavy metal contaminated soil or water resources. The other group of plants transformed to express heavy metal exclusion pump show reduced lead and cadmium content, which makes them heavy metal-safe plants. When her work was recently published in Nature Biotechnology (2003), it was received with surprise both at home and abroad. Particularly, in Switzerland, Dr. Lee’s work was broadcast in two national TV networks. They notices that the genetically modified plants developed by Dr. Lee would successfully eliminate toxic heavy metals from the environment. However, application of this technology is not limited to cleaning up the environment. The most critical path in which humans are exposed to heavy metals is through dietary intakes, and this problem can be ameliorated when Dr. Lee’s technology is applied to crop plants. When applied to tobacco plants, this technology will reduce health risks or tobacco smokers by reducing cadmium content of cigarettes. (Nature Biotech, 2003)
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Professor Gynheung An
Rice as a model crop |
Rice is one of the three major crops in the world together with corn and wheat. Although their genomic composition is similar, wheat and corn genomes are at least ten times as large as rice genomes and are polyploidy. Thus, rice was chosen as the model crop to complete sequencing genomic structure. To effectively elucidate the functional roles of rice genomes counting over 60,000, Professor Gynheung An’s research team established two groups of mutants in rice. The first group consists of simple mutants, whose genomic function is inactivated, whereas the second group consists of mutants whose function is activated. To increase the utility of mutant lines they7 are tagged with T-DNA for ready identification. Professor An’s team, using Dongjin Rice, have successfully established rice mutant lines counting over 100,000. They also generated databases for the T-DNA insertion sites of over 20,000 lines. This is the sole and the largest project of rice functional genomics in the world. His laboratory has been conducting cooperative researches with over 50 laboratories from ten countries worldwide with an ultimate goal to produce rice with high nutrition and functional variety. ( Nature News Feature ,2003)
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Hyung Joon Cha 
