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Kobe University and the National Institute of Advanced Industrial Science and Technology (AIST) in Japan have developed a technology enabling the selection of proteins with a high affinity for drug target molecules (also proteins) on cell membranes. This discovery will advance research targeting membrane proteins linked to diseases such as cancer, and therefore has potential applications in the development of new biopharmaceuticals. The results of this research were published in the British science journal Scientific Reports on 19th November 2015 at 10am GMT. This discovery is a result of joint research carried out by Kobe University doctoral student in the Graduate School of Engineering Kaishima Misato, Associate Professor at the Organization of Advanced Science and Technology Ishii Jun, Professor at the Graduate School of Engineering Kondo Akihiko, and Senior Researcher at the AIST Biomedical Research Institute Molecular and Cellular Breeding Research Group Fukuda Nobuo. The defining feature of this research is that by using the yeast signal transduction machinery1 and the competitive protein binding principle, the group was able to identify mutant proteins2 that possessed an enhanced ability to bind with membrane proteins. Membrane proteins play a vital role in controlling the physiological functions of living organisms, and abnormalities in these physiological functions cause diseases such as cancer. This means that molecules which can bind with membrane proteins and regulate physiological functions are potential candidates for drug development. The research team focused on the signal transduction machinery of yeast cells, which share many traits with human cells. Using the knowledge that the localization of signaling molecules on membranes is essential for the growth of yeast cells, they developed a method to select the proteins which bind with "membrane proteins". Following this, by artificially creating an intracellular environment in which proteins competed to bind with each other, the research group enabled the selection of mutant proteins with an enhanced affinity for membrane proteins. They demonstrated that this procedure could be applied to human epidermal growth factor receptors3, a major target molecule for cancer treatment. By identifying proteins that have a high affinity for membrane proteins, this technology facilitates the creation of new biopharmaceuticals for various drug targets. It could also potentially increase speed and reduce costs in the drug development process. Explore further: 'MaMTH' advance: New technology sheds light on protein interactions More information: Misato Kaishima et al. Gγ recruitment systems specifically select PPI and affinity-enhanced candidate proteins that interact with membrane protein targets, Scientific Reports (2015). DOI: 10.1038/srep16723

Hasunuma T.,Organization of Advanced Science and Technology | Ismail K.S.K.,University Malaysia Perlis | Ismail K.S.K.,Kobe University | Nambu Y.,Kobe University | Kondo A.,Kobe University
Journal of Bioscience and Bioengineering | Year: 2014

Lignocellulosic biomass dedicated to bioethanol production usually contains pentoses and inhibitory compounds such as furfural that are not well tolerated by Saccharomyces cerevisiae. Thus, S.cerevisiae strains with the capability of utilizing both glucose and xylose in the presence of inhibitors such as furfural are very important in industrial ethanol production. Under the synergistic conditions of transaldolase (TAL) and alcohol dehydrogenase (ADH) overexpression, S. cerevisiae MT8-1X/TAL-ADH was able to produce 1.3-fold and 2.3-fold more ethanol in the presence of 70mM furfural than a TAL-expressing strain and a control strain, respectively. We also tested the strains' ability by mimicking industrial ethanol production from hemicellulosic hydrolysate containing fermentation inhibitors, and ethanol production was further improved by 16% when using MT8-1X/TAL-ADH compared to the control strain. Transcript analysis further revealed that besides the pentose phosphate pathway genes TKL1 and TAL1, ADH7 was also upregulated in response to furfural stress, which resulted in higher ethanol production compared to the TAL-expressing strain. The improved capability of our modified strain was based on its capacity to more quickly reduce furfural in situ resulting in higher ethanol production. The co-expression of TAL/ADH genes is one crucial strategy to fully utilize undetoxified lignocellulosic hydrolysate, leading to cost-competitive ethanol production. © 2013 The Society for Biotechnology, Japan. Source

Chen C.,Kobe University | Shiotani S.,Organization of Advanced Science and Technology | Sasa K.,Kobe University
Ocean Engineering | Year: 2013

Sea states, such as waves, tidal currents, and wind are important factors for safe and economic ship navigation. In previous papers of Xia et al. (2006a, 2006b) single factor generated by low pressure was studied independently. The objective of this paper is to study how ship navigation is affected by the combined effects of these factors. For clarification, simulations of two representative typhoons were conducted, and the results were compared. Numerical simulations of tidal currents, waves, and wind were applied to provide high-resolution information, which was then used to simulate ship navigation. Estimation of ship position was found effectively by comparing the results from these two cases and using the proposed numerical navigation simulation method. © 2013 Elsevier Ltd. Source

Ismail K.S.K.,Kobe University | Ismail K.S.K.,University Malaysia Perlis | Sakamoto T.,Kobe University | Hasunuma T.,Organization of Advanced Science and Technology | And 2 more authors.
Biotechnology Journal | Year: 2014

Lignocellulosic biomass is a potential substrate for ethanol production. However, pretreatment of lignocellulosic materials produces inhibitory compounds such as acetic acid, which negatively affect ethanol production by Saccharomyces cerevisiae. Supplementation of the medium with three metal ions (Zn2+, Mg2+, and Ca2+) increased the tolerance of S. cerevisiae toward acetic acid compared to the absence of the ions. Ethanol production from xylose was most improved (by 34%) when the medium was supplemented with 2 mM Ca2+, followed by supplementation with 3.5 mM Mg2+ (29% improvement), and 180 μM Zn2+ (26% improvement). Higher ethanol production was linked to high cell viability in the presence of metal ions. Comparative transcriptomics between the supplemented cultures and the control suggested that improved cell viability resulted from the induction of genes controlling the cell wall and membrane. Only one gene, FIT2, was found to be up-regulated in common between the three metal ions. Also up-regulation of HXT1 and TKL1 might enhance xylose consumption in the presence of acetic acid. Thus, the addition of ionic nutrients is a simple and cost-effective method to improve the acetic acid tolerance of S. cerevisiae. Acetic acid from the pretreatment of lignocellulosic materials is inhibitory to Saccharomyces cerevisiae during ethanol production. Addition of metal ions such as Zn, Mg and Ca into the fermentation media increases the yeast's tolerance to acetic acid, resulting in improved ethanol production. This metal supplementation can be a simple and cost-effective method to improve acetic acid tolerance of S. cerevisiae for ethanol production under acidic conditions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Ismail K.S.K.,Kobe University | Ismail K.S.K.,University Malaysia Perlis | Sakamoto T.,Kobe University | Hatanaka H.,Suntory Research Center | And 2 more authors.
Journal of Biotechnology | Year: 2013

Production of ethanol from xylose at high temperature would be an economical approach since it reduces risk of contamination and allows both the saccharification and fermentation steps in SSF to be running at elevated temperature. Eight recombinant xylose-utilizing Saccharomyces cerevisiae strains developed from industrial strains were constructed and subjected to high-temperature fermentation at 38 °C. The best performing strain was sun049T, which produced up to 15.2. g/L ethanol (63% of the theoretical production), followed by sun048T and sun588T, both with 14.1. g/L ethanol produced. Via transcriptomic analysis, expression profiling of the top three best ethanol producing strains compared to a negative control strain, sun473T, led to the discovery of genes in common that were regulated in the same direction. Identification of the 20 most highly up-regulated and the 20 most highly down-regulated genes indicated that the cells regulate their central metabolism and maintain the integrity of the cell walls in response to high temperature. We also speculate that cross-protection in the cells occurs, allowing them to maintain ethanol production at higher concentration under heat stress than the negative controls. This report provides further transcriptomics information in the interest of producing a robust microorganism for high-temperature ethanol production utilizing xylose. © 2012 Elsevier B.V. Source

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