Updated on 2026/06/02

写真a

 
SHIMANOUCHI Toshinori
 
Organization
Faculty of Environmental, Life, Natural Science and Technology Associate Professor
Position
Associate Professor
External link

Degree

  • (BLANK) ( Osaka University )

Research Interests

  • 化学工学

  • Surface Science

  • Separation Science

  • biosensor

  • liposome

  • vesicle

  • amyloid

  • Chemical process design

  • subcritical water

Research Areas

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Transport phenomena and unit operations  / 晶析、反応分離、亜臨界水

  • Life Science / Biophysics  / 脂質膜、タンパク質の動的機能

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Biofunction and bioprocess engineering  / バイオプロセスのためのソフトマター/ソフト界面設計

  • Manufacturing Technology (Mechanical Engineering, Electrical and Electronic Engineering, Chemical Engineering) / Chemical reaction and process system engineering  / 環境プロセス設計、ハイブリッド触媒設計に基づくプロセス強化

Education

  • Osaka University   大学院基礎工学研究科   物質創成専攻 化学工学領域 博士後期課程中退

    1998.4 - 2000.12

    　 More details

    Country： Japan

    researchmap

  • Osaka University   大学院基礎工学研究科   物質創成専攻 化学工学領域 博士前期課程

    1997.4 - 1998.3

    　 More details

  • Osaka University   基礎工学部   化学工学科

    1992.4 - 1997.3

    　 More details

    Country： Japan

    researchmap

Research History

  • Okayama University   学術研究院 環境生命科学学域   Associate Professor

    2021.4

    　 More details

    Country：Japan

    researchmap

  • Okayama University   The Graduate School of Environmental and Life Science   Associate Professor

    2012.10 - 2021.3

    　 More details

  • Nara National College of Technology

    2006.4 - 2007.3

    　 More details

  • Osaka University   Graduate School of Engineering Science

    2001.1 - 2012.9

    　 More details

Professional Memberships

Committee Memberships

  • 化学工学会中国四国支部   事務局  

    2023.4   

    　 More details

    Committee type：Academic society

    researchmap

  • 分離技術会   編集委員  

    2022.11   

    　 More details

    Committee type：Academic society

    researchmap

  • 分離技術会   総務委員  

    2022.7   

    　 More details

    Committee type：Academic society

    researchmap

  • 分離技術会関西支部   会計  

    2022.4   

    　 More details

    Committee type：Academic society

    researchmap

  • 膜学会   編集委員  

    2017.4   

    　 More details

    Committee type：Academic society

    researchmap

  • 表面真空学会   ソフトマター部会庶務  

    2017.4   

    　 More details

    Committee type：Academic society

    researchmap

  • 表面真空学会   編集委員  

    2016.4   

    　 More details

    Committee type：Academic society

    researchmap

  • 生物工学会   関西支部委員  

    2002.4 - 2012.9   

    　 More details

    Committee type：Academic society

    生物工学会

    researchmap

▼display all

 

Papers

▼display all

Books

  • 晶析操作の実務

    島内寿徳（ Role： Contributor ,  タンパク質の晶析操作の注意点と最近の進展）

    株式会社 情報機構  2023.11  （ ISBN:9784865022599 ）

    　More details

  • 分離プロセスの最適化とスケールアップの進め方

    島内 寿徳, 白髭 勇季, 木村 幸敬（ Role： Contributor ,  4章9節，p227—237 (モデル生体膜を用いるタンパク質の晶析操作)）

    技術情報協会  2019.11 

    　More details

  • 分離技術のシーズとライセンス技術の実用化

    島内 寿徳（ Role： Contributor ,  マイクロキャピラリー型水熱反応分離装置の応用技術）

    分離技術会編  2018.3 

    　More details

    Language：Japanese Book type：Scholarly book

    researchmap

  • Pharmaceutical Process Chemistry

    Hiroshi Umakoshi, Toshinori Shimanouchi, Ryoichi Kuboi（ Role： Contributor ,  Chapter 21, 421-441 (Development of LIPOzyme Based on Biomembrane Process Chemistry)）

    Wiley VCH  2010 

    　More details

  • 進化する有機半導体

    島内 寿徳, 久保井亮一（ Role： Contributor ,  7章2節，p422-430 (導電性高分子/人工細胞膜を用いたストレスセンサの開発)）

    NTS  2006 

    　More details

  • リポソーム応用の新展開 ~人工細胞の開発に向けて~

    久保井 亮一, 島内 寿徳（ Role： Contributor ,  2章2節2，p38-45 (セルサイズリポソームの調製), 9章1節，p472-482 (固定化リポソームクロマトグラフィー), 9章2節，p483-493 (固定化リポソームセンサーとタンパク質の構造異常診断)）

    NTS  2005 

    　More details

  • Study on stress mediated behaviour and preparation of giant vesicles

    Toshinori Shimanouchi, Hiroshi Umakoshi, Ryoichi Kuboi（ Role： Contributor ,  Chapter 26, p.369-377）

    John Wiley & Sons  2000 

    　More details

  • Utilization of Heat Stress Mediated Translocation across Phospholipid Membrane for Protein Separation

    ADVANCES IN BIOSEPARATION ENGINEERING 1996-1997  1998 

    　More details

▼display all

MISC

  • BXを目指した資源循環のための 環境低負荷なバイオマス変換法の開発 Invited

    島内寿徳, 木村幸敬

    分離技術   54 ( 4 )   220 - 226   2024.9

    　More details

    Authorship：Lead author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • Self-assemblies of amyloid beta peptides on glycolipid-embedded membranes Invited

    Toshinori Shimanouchi

    IVSST2023   2Gp01   2023.11

    　More details

    Authorship：Lead author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (international conference proceedings)  

    researchmap

  • Chemical Process of 5-Hydroxymethylfurfural by Using a Slug Flow of Water/Organic Biphasic Invited

    SHIMANOUCHI TOSHINORI, KIMURA YUKITAKA, FUJIOKA SATOKO, TERASAKA KOICHI

    87 ( 1 )   22 - 25   2023.1

    　More details

    Authorship：Lead author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • Production of a Monomer of a Biomass Plastic from Woody Biomass~Three Chemical Processes Using Water as Key Technology~

    木村幸敬, 島内寿徳

    水環境学会誌   44(A) ( 7 )   2021

    　More details

  • Cholesterolと非イオン界面活性剤からなる自己集合体の階層的疎水性の違いによる分子の局在性への影響

    太田ひかる, 林啓太, 杉村春奈, 島内寿徳, 岩崎智之, 中村秀美

    化学工学会秋季大会研究発表講演要旨集(CD-ROM)   52nd   2021

    　More details

  • Role of Dynamic Space in Lipid Membranes for the Reaction Field

    福間早紀, 島内寿徳, 木村幸敬

    膜   45 ( 3 )   2020

    　More details

  • 水素発生を目指したリポソーム/単層カーボンナノチューブ/フラロデンドロン光触媒複合材料の評価

    寺井公亮, 島内寿徳, 内藤雅晴, 袴塚響, 田嶋智之, 高口豊, 木村幸敬

    化学工学会年会研究発表講演要旨集(CD-ROM)   85th   2020

    　More details

  • Analysis of Microscopic Dynamics of Membrane Interfaces Based on Dielectric Measurement

    島内寿徳, 福間早紀, 木村幸敬

    表面と真空   62 ( 4 )   2019

    　More details

  • 凍結工程制御に基づく凍結乾燥とPAT技術 Invited

    川崎 英典, 島内 寿徳, 木村 幸敬

    分離技術   48 ( 6 )   37 - 46   2018.12

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • Molecular Recognition/Transformation Based on Membrane Dynamics

    41 ( 5 )   244 - 250   2016.9

    　More details

  • Evaluation of the interaction between amyloid beta and lipid membranes by means of ToF-SIMS

    Yokoyama Yuta, Shimanouchi Toshinori, Iwai Hideo, Aoyagi Satoka

    Abstract of annual meeting of the Surface Science of Japan   35th   12 - 24   2015.12

    　More details

    Language：Japanese   Publisher：The Surface Science Society of Japan  

    DOI： 10.14886/sssj2008.35.0_24

    CiNii Article

    J-GLOBAL

    researchmap

  • Discrimination of Target Proteins Using Array Sensor with Liposome Encapsulating Fluorescent Molecules

    32   1 - 4   2015.10

    　More details

    Language：English   Publisher：Institute of Electrical Engineers of Japan  

    CiNii Article

    researchmap

  • 木質バイオマスの亜臨界水抽出と撥水性界面形成への応用 Invited

    島内寿徳, 神庭朋也, Wei Yang, 木村幸敬

    ケミカルエンジニヤリング   59 ( 7 )   66 - 71   2014.9

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    researchmap

  • A “Membranome”―Based Approach toward “Bio‐Inspired Membrane”

    馬越大, 島内寿徳, 菅恵嗣

    膜   37 ( 6 )   264 - 269   2012.11

    　More details

    Language：Japanese   Publisher：THE MEMBRANE SOCIETY OF JAPAN  

    It is important to establish a methodology to design and develop a "Bio-Inspired Membrane", which can be defined as an "Artificial Membrane" inspired by structures and functions observed in "Biomembrane". Several approaches relating to this research area are reviewed based on a hierarchical view about the structures and characteristics of the above membranes. A "Membranome" research utilizing a gel membrane immobilizing liposome membrane at high concentration is herewith introduced as one of several approaches to create the "Bio-Inspired Membrane". Some possible data required for the "Bio-Inspired Membrane" are finally discussed, focusing on the physicochemical property of self-assembly included in a total system.

    DOI： 10.5360/membrane.37.264

    CiNii Article

    CiNii Books

    J-GLOBAL

    researchmap

  • Poster Session

    YOSHIMUNE Miki, KUMAKIRI Izumi, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori

    37 ( 6 )   301 - 303   2012.11

    　More details

  • Leakage Current Microsensor Using Liposome Entrapping Electrolyte for Detection of Target Protein

    TAKADA Keisuke, OHARA Yuri, YAMASHITA Kaoru, NODA Minoru, SHIMANOUCHI Toshinori, UMAKOSHI Hiroshi

    2012 ( 8 )   15 - 19   2012.6

    　More details

  • 人工細胞膜上におけるアミロイド形成 Invited Reviewed

    島内 寿徳, 北浦 奈知, 馬越 大, 久保井 亮一

    表面科学   33   40 - 46   2012

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • 生体膜晶析工学の創成に関する基礎工学的研究 Invited

    島内 寿徳

    膜   36   233 - 239   2011

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • New Planar-Type Leakage Current and Impedance Microsensor for Detection of Interaction between Electrolyte-Entrapping Liposome and Protein

    P. Lorchirachoonkul, I. Goto, T. Shimanouchi, K. Yamashita, M. Noda

    EUROSENSORS XXV   25   1449 - 1452   2011

    　More details

  • Significant improvement in sensitivity of leakage current microsensor by using denaturant and electrolyte-entrapping DPPC liposomes

    P. Lorchirachoonkul, T. Shimanouchi, K. Yamashita, H. Umakoshi, R. Kuboi, M. Noda

    14th International Conference on Miniaturized Systems for Chemistry and Life Sciences 2010, MicroTAS 2010   3   1982 - 1984   2010.12

    　More details

  • As-Lipozyme: Characterization of Its Activity Like Antioxidative Enzymes

    L. Q. Tuan, T.T.T. Huong, H. Umakoshi, T. Shimanouchi, R. Kuboi, K. Shiomori, Y. Baba

    Proc. 2nd International Symposium on Health Hazards of Arsenic Contamination   138 - 142   2010.5

    　More details

    Language：English  

    researchmap

  • 生体膜界面を晶析場とするタンパク質のアミロイド形成/多形の制御 Invited

    島内 寿徳, 北浦 奈知, 大西 諒, 馬越 大, 久保井 亮一

    分離技術   40 ( 6 )   455 - 462   2010

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：分離技術会  

    CiNii Article

    CiNii Books

    researchmap

  • 脂質膜界面特性に基づくベシクル形成制御

    島内 寿徳, 馬越 大, 久保井 亮一, 石井 治之, 吉本 則子

    化学工学シンポジウムシリーズ   81   107 - 114   2010

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (other)  

    researchmap

  • 2P-1101 Cotrol of polymorphism of amyloid by liposome membranes

    SHIMANOUCHI Toshinori, OHNISHI Ryo, KITAURA Nashi, UMAKOSHI Hiroshi, KUBOI Ryoichi

    22   34 - 34   2010

    　More details

  • MN-P26 Development of membrane chip system for study on membrane-protein interaction(Section X Micro/Nano Technology for Analysis and Cell Manipulation)

    Shimanouchi Toshinori, Ishii Haruyuki, Oyama Ena, Shimauchi Naoya, Umakoshi Hiroshi, Kuboi Ryoichi

    Journal of bioscience and bioengineering   108 ( 1 )   S162 - S163   2009.11

    　More details

    Language：English   Publisher：The Society for Biotechnology, Japan  

    CiNii Article

    CiNii Books

    researchmap

  • BE-P3 Preparation of liposome immobilized membrane module and its application(Section V Biomolecular Engineering and Bioseparation)

    Umakoshi Hiroshi, Sugaya Hiroyuki, Tohtake Yuji, Shimanouchi Toshinori, Kuboi Ryoichi

    Journal of bioscience and bioengineering   108 ( 1 )   S65   2009.11

    　More details

    Language：English   Publisher：The Society for Biotechnology, Japan  

    CiNii Article

    CiNii Books

    researchmap

  • Leakage Current Microsensor for Detection of Interaction between Electrolyte-entrapping Liposome and Protein

    ARINOBE Yasushi, ASAI Takeshi, YAMASHITA Kaoru, NODA Minoru, SHIMANOUTI Toshinori, UMAKOSHI Horoshi, OKUYAMA Masanori, KUBOI Ryouichi

    電気学会研究会資料. BMS, バイオ・マイクロシステム研究会 = The papers of Technical Meeting on Bio Micro Systems, IEE Japan   2009 ( 8 )   57 - 60   2009.7

    　More details

    Language：Japanese  

    CiNii Article

    researchmap

  • メンブレン・ストレスバイオテクノロジーとアルツハイマー病の診断

    馬越大, 島内寿徳, 久保井亮一

    分離技術   39 ( 2 )   109 - 114   2009.3

    　More details

  • LIPOzyme: Basic and Its Possible Application

    2009

    　More details

  • Immobilization of Liposome on Solid Surface: A Quartz Microbalance Study

    J. Colloid Surface Interf.   in press (2009)   2009

    　More details

  • Negatively-Charged Liposome is Potent Inhibitor of Protein Folding in Post-Translational Process of in vitro Gene Expression

    Biochem. Eng. J.   in press (2009)   2009

    　More details

  • 1Ep18 Characterization of surface property of amyloidgenic proteins : The use of membrane chip analysis (Part 1)

    Shimanouchi Toshinori, Huong Thi Vu, Shimauchi Naoya, Umakoshi Hiroshi, Kuboi Ryoichi

    21   56 - 56   2009

    　More details

  • 2Fp06 Analysis of Cell Surface Factor involved in Yeast Flocculation

    ASAYAMA Tomohiro, SHIMANOUCHI Toshinori, UMAKOSHI Hiroshi, KUBOI Ryoichi, TACHIBANA Taro, AZUMA Masayuki

    21   78 - 78   2009

    　More details

  • 1Ep20 Amyloid fibril formation on lipid membrane and its polymorphism (Part 3)

    Shimanouchi Toshinori, Shimauchi Naoya, Onishi Ryo, Umakoshi Hiroshi, Kuboi Ryoichi

    21   57 - 57   2009

    　More details

  • 1Ep19 Monitoring of amyloid fibril formation on lipid membranes with Membrane Chip (Part 2)

    Shimanouchi Toshinori, Huong Thi Vu, Umakoshi Hiroshi, Kuboi Ryoichi

    21   56 - 56   2009

    　More details

  • Bio-thermochemical sensor of microbolometer with a small amount of immobilized liposome on Pt surface

    ASAI Takeshi, YAMASHITA Kaoru, NODA Minoru, SHIMANOUCHI Toshinori, OKUYAMA Masanori, KUBOI Ryoichi

    2008 ( 1 )   31 - 34   2008.6

    　More details

  • Characterization of Surface Properties of Streptomyces griseus Cell after Heat Treatment with Liposome Using Aqueous Two-Phase Method

    2008

    　More details

  • Cutting Edge of Membrane Stress Biotechnology

    KUBOI Ryoichi, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori

    Membrane   33(6), 300-306 (2008) ( 6 )   300 - 306   2008

    　More details

    Language：Japanese   Publisher：THE MEMBRANE SOCIETY OF JAPAN  

    A "Biomembrane"is a key interface to integrate production and separation of target materials through the creationof "new order"on its surface. A model biomembrane, liposome, can recognize (separate)the (bio)moleculesthrough (i)electrostatic, (ii)hydrophobic interaction, and (iii)stabilization effect of hydrogen bonds in the hydropho-bic lipid environment. A novel biomembrane-based catalysis (LIPOzyme: liposome + enzyme)can be designed anddeveloped by integrating the above recognition sites and a simple catalytic center on the liposome surface. A processdesign utilizing LIPOzyme chemistry and the recognition (bioseparation)functions of model-biomembrane (lipo-some)is the basic strategy to achieve a "Biomembrane Process Chemistry"as an application of "Membranomics".

    DOI： 10.5360/membrane.33.300

    CiNii Article

    CiNii Books

    researchmap

    Other Link： https://jlc.jst.go.jp/DN/JALC/00322917093?from=CiNii

  • Cutting-Edge of Membrane Stress Biotechnology

    KUBOI Ryoichi, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori

    MEMBRANE   33(6), 300-306 (2008) ( 6 )   300 - 306   2008

    　More details

    Language：Japanese   Publisher：THE MEMBRANE SOCIETY OF JAPAN  

    A "Biomembrane"is a key interface to integrate production and separation of target materials through the creationof "new order"on its surface. A model biomembrane, liposome, can recognize (separate)the (bio)moleculesthrough (i)electrostatic, (ii)hydrophobic interaction, and (iii)stabilization effect of hydrogen bonds in the hydropho-bic lipid environment. A novel biomembrane-based catalysis (LIPOzyme: liposome + enzyme)can be designed anddeveloped by integrating the above recognition sites and a simple catalytic center on the liposome surface. A processdesign utilizing LIPOzyme chemistry and the recognition (bioseparation)functions of model-biomembrane (lipo-some)is the basic strategy to achieve a "Biomembrane Process Chemistry"as an application of "Membranomics".

    DOI： 10.5360/membrane.33.300

    CiNii Article

    CiNii Books

    researchmap

    Other Link： https://jlc.jst.go.jp/DN/JALC/00322917093?from=CiNii

  • Immobilized Liposome Chromatography/Bio-Membrane Module for Bioseparation and Bioreactor

    2008

    　More details

  • LIPOzyme Design Based on Molecular Recognition Function of Liposome -Biomembrane Process Chemistry and Separation Technology-

    2008

    　More details

  • Separation and Analysis for Aβ Peptides Based on Recognition Function of Abnormal Biomembrane ~Membrane Chip Analysis Can Brighten a Potential Aspect of Alzheimer’s Disease~

    2008

    　More details

  • Cationic Liposome DOTAP can Knock-out mRNA and Silence Its Translation in E.coli Cell Free Translation System

    2008

    　More details

  • Simple Ligand/Porphyrin Complex can Induce Both SOD and POD Activities Similar to Those of Metal-Ligand Complex

    2008

    　More details

  • Preparation and Properties of Antioxidative LIPOzyme

    2008

    　More details

  • Biomembrane Process Chemistry and Separation Technology~ Design and Development of Antioxidative LIPOzyme in One-Pot Based on Molecular Recognition Function of Liposome

    2008

    　More details

  • LIPOzyme design based on molecular recognition function of liposome

    2008

    　More details

  • Amyloid fibril formation on biomembrane: Analysis using membrane chip system

    2008

    　More details

  • IMMOBILIZED-LIPOSOME SENSOR SYSTEM FOR DETECTION OF DAMAGED PROTEINS

    Kuboi R., Morita S., V. T. Huong, Ishii H., Shimanouchi T., Umakoshi H.

    Annual Report of FY 2007, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   120 - 124   2008

    　More details

    Language：English   Publisher：Core University Program Office, Ike Laboratory, Div. of Sustainable Energy and Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • Liposome-Assisted Refolding of Microbial Transglutaminase

    UMAKOSHI Hiroshi, YOSHIMOTO Noriko, YOSHIMOTO Makoto, SHIMANOUCHI Toshinori, KUBOI Ryoichi

    Membrane   32 ( 5 )   287 - 293   2007.9

    　More details

  • Immobilized Liposome Sensor and Its Application to Membrane-Related Diseases Invited

    KUBOI Ryoichi, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori

    MEMBRANE   32 ( 1 )   32 - 39   2007

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：THE MEMBRANE SOCIETY OF JAPAN  

    The diseases caused by the membrane disorder or damages are categorized as the Membrane-related diseases. Alzheimer's disease (AD), which is one of the membrane-related diseases, has been considered to be accompanied by the oxidative damage of the neuronal cell membrane. Amyloid β-peptide (Aβ), which is a pathological key peptide of AD, interacts with biomembrane and this interaction has been recently paid attention from the viewpoints of not only conformational abnormality but also the influence to biomembrane. And therefore, the modeling of biomembrane using liposome has been desired to develop the liposome-based sensor system. In this article, we surveyed the sensor system using liposome. Firstly, the immobilization techniques for preparation of the immobilized-liposome sensor are surveyed. Secondary, some kinds of sensor have been introduced: (i) (metal affinity) immobilized-liposome chromatography, (ii) immobilized-liposome quartz crystal microbalance method, (iii) immobilized-liposome sensor (Amperometric method), (iv) membrane chip system. These techniques have been developed in a framework of "Membrane Stress Biotechnology". The above methodologies could provide us the quantitative properties of stress responsive function of both the protein and the membrane.

    DOI： 10.5360/membrane.32.32

    CiNii Article

    CiNii Books

    researchmap

    Other Link： https://jlc.jst.go.jp/DN/JALC/00289812370?from=CiNii

  • Immobilized Liosome Sensor and Its Application to Membrane-Related Diseases

    KUBOI Ryoichi, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori

    MEMBRANE   32(1), 32-39 ( 1 )   32 - 39   2007

    　More details

    Language：Japanese   Publisher：THE MEMBRANE SOCIETY OF JAPAN  

    The diseases caused by the membrane disorder or damages are categorized as the Membrane-related diseases. Alzheimer's disease (AD), which is one of the membrane-related diseases, has been considered to be accompanied by the oxidative damage of the neuronal cell membrane. Amyloid β-peptide (Aβ), which is a pathological key peptide of AD, interacts with biomembrane and this interaction has been recently paid attention from the viewpoints of not only conformational abnormality but also the influence to biomembrane. And therefore, the modeling of biomembrane using liposome has been desired to develop the liposome-based sensor system. In this article, we surveyed the sensor system using liposome. Firstly, the immobilization techniques for preparation of the immobilized-liposome sensor are surveyed. Secondary, some kinds of sensor have been introduced: (i) (metal affinity) immobilized-liposome chromatography, (ii) immobilized-liposome quartz crystal microbalance method, (iii) immobilized-liposome sensor (Amperometric method), (iv) membrane chip system. These techniques have been developed in a framework of "Membrane Stress Biotechnology". The above methodologies could provide us the quantitative properties of stress responsive function of both the protein and the membrane.

    DOI： 10.5360/membrane.32.32

    CiNii Article

    CiNii Books

    researchmap

    Other Link： https://jlc.jst.go.jp/DN/JALC/00289812370?from=CiNii

  • DESIGN AND DEVELOPMENT OF MEMBRANE CHIP SYSTEM FOR STRESS SENSOR

    Umakoshi Hiroshi, Shimanouchi Toshinori, Kuboi Ryoichi

    Annual Report of FY 2006, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   21 - 24   2007

    　More details

    Language：English   Publisher：Core University Program Office, Ike Laboratory, Div. of Sustainable Energy and Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • 3C10-4 Effect of Hydrophobicity of Abeta Oligomer Cross-Linked by Transglutaminase on Amyloid Fibril Formation

    UMAKOSHI Hiroshi, HAMADA Satoshi, SHIMANOUCHI Toshinori, KUBOI Ryoichi

    19   90 - 90   2007

    　More details

  • 3C10-5 Roles of Liposomes and Heat Stress for Enhanced Release of Chitosanase from Streptomyces griseus :

    NGO Kien Xuan, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori, KUBOI Ryoichi

    19   91 - 91   2007

    　More details

  • 1B11-1 Analysis of amyloid fibril formation based on the surface property of protofibrils

    SHIMANOUCHI Toshinori, HIROIWA Azusa, NISHIYAMA Keiichi, UMAKOSHI Hiroshi, KUBOI Ryoichi

    19   59 - 59   2007

    　More details

  • DEVELOPMENT OF ELECTROACTIVE POLYMETHYLTHIOPHENE BASED DOPAMINE SENSOR

    Vu Thi Huong, Kuboi Ryoichi, Pham Hung Viet, Shimanouchi Toshinori, Nguyen Minh Tue, Do Phuc Quan

    Annual Report of FY 2006, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   41 - 46   2007

    　More details

    Language：English   Publisher：Core University Program Office, Ike Laboratory, Div. of Sustainable Energy and Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • DESIGN AND DEVELOPMENT OF OXIDATIVE STRESS RESPONSIVE LIPOSOME MEMBRANE WITH ENZYMATIC ACTIVITY (LIPOZYME) AND ITS APPLICATION TO CHEMICAL/BIOSENSOR

    Kuboi Ryoichi, Shimanouchi Toshinori, Umakoshi Hiroshi, Le Quoc Tuan

    Annual Report of FY 2006, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   63 - 66   2007

    　More details

    Language：English   Publisher：Core University Program Office, Ike Laboratory, Div. of Sustainable Energy and Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • Design of Stress Sensor Using Conducting Polymers/Artificial Cell Membranes

    7章2節   2006

    　More details

  • LIPOzyme: design and development of artificial chaperone/enzyme liposome

    2006

    　More details

  • Design of stress-mediated bioprocess using liposome - recovery of chitosanase from Streptomyces griseus cells

    2006

    　More details

  • Study on Interaction of Amyloid b-Peptide with Liposome

    2006

    　More details

  • Stress-mediated preparation of liposomes incorporating membrane protein

    2006

    　More details

  • Membrane Chip: Dynamic Analysis of Stressed Membrane-Membrane Interaction

    2006

    　More details

  • Membrane Stress Biotechnology

    2006

    　More details

  • Use LIPOzyme for Stress-Mediated Bioreactor and Bioseparation

    2006

    　More details

  • 1F12-1 SOD Activity with Support of Phospholipid Membrane under Oxidative Stress :

    TUAN Le quoc, NAGAMI Hideto, UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori, KUBOI Ryoichi

    18   94 - 94   2006

    　More details

  • 2F11-4 Metaloenzymatic function of Amyloid beta-metal complex on liposome membrane : cholesterol oxidation

    TASAKI Makoto, YOSHIMOTO Noriko, SHIMANOUCHI Toshinori, UMAKOSHI Hiroshi, KUBOI Ryoichi

    18   102 - 102   2006

    　More details

  • 2F09-4 Study on solubilizaiton of amyloid fibril by oxidative derivatives of dopamine

    SHIMANOUCHI Toshinori, ISHIKAWA Daisuke, NOZAWA Atsushi, UMAKOSHI Hiroshi, KUBOI Ryoichi

    18   99 - 99   2006

    　More details

  • 2G09-4 Evaluation of SOD-like activity of artificial enzymatice liposome modified with multi-nuclear metal

    OHAMA Yuji, TUAN Le Quoc, SHIMANOUCHI Toshinori, UMAKOSHI Hiroshi, KUBOI Ryoichi

    18   120 - 120   2006

    　More details

  • Development of Chemical-and Bio-sensor for Environmental Monitoring

    Shimanouchi Toshinori, Kuboi Ryoichi

    Annual Report of FY 2005, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   41 - 46   2006

    　More details

    Language：English   Publisher：Core University Program Office, Ike Laboratory, Div. of Sustainable Energy and Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • Preparation Method of Cell-Sized Liposomes

    38-45   2005

    　More details

  • Immobilized Liposome Chromatography

    472-482   2005

    　More details

  • Metal-affinity immobilized liposome chromatography to detect conformational change of peptide

    2005

    　More details

  • Heat enhanced recovery of chitosanase from Streptomyces griceus using aqueous two-phase system

    2005

    　More details

  • Detection of Conformational Change of Protein Based on Protein-Liposome Interaction

    2005

    　More details

  • Metal affinity-immobilized liposome chromatography for detection of conformational change of peptide

    2005

    　More details

  • タンパク質の構造異常疾患におけるアミロイド線維の制御 〜メンブレン・ストレスバイオテクノロジーの視点から〜 Invited

    島内 寿徳, 馬越 大, 久保井 亮一

    分離技術   35 ( 6 )   391 - 396   2005

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • DESIGN AND DEVELOPMENT OF NANO-ARTIFICIAL-CELL MEMBRANE BASED NOVEL BIOSENSOR : APPLICATION FOR MONITORING OF AQUEOUS STRESSES

    Kuboi Ryoichi, Morita Seiichi, Yoshimoto Makoto, Ho-Sup Jung, Shimanouchi Toshinori, Umakoshi Hiroshi

    Annual Report of FY 2004, The Core University Program between Japan Society for the Promotion of Science (JSPS) and Vietnamese Academy of Science and Technology (VAST)   13 - 16   2005

    　More details

    Language：English   Publisher：Core University Program Office, Fujita Laboratory, Dept. of Environmental Engineering, Osaka University  

    CiNii Article

    researchmap

  • メンブレン・ストレス応答ダイナミクスのモニタリング技術の開発 Invited

    島内 寿徳, 森田 誠一, 久保井 亮一

    生物工学会誌   82 ( 5 )   208 - 211   2004

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：日本生物工学会  

    CiNii Article

    CiNii Books

    researchmap

    Other Link： http://dl.ndl.go.jp/info:ndljp/pid/10514808

  • Detection of Protein Conformation under Stress Condition Using Liposome as Sensor Materials

    2004

    　More details

  • メンブレン・ストレスバイオテクノロジー 〜薬物送達システムの設計と開発への応用〜

    49 ( 4 )   255 - 260   2004

    　More details

  • メンブレン・ストレスバイオテクノロジー ～薬物送達システムの設計と開発への応用～

    49 ( 4 )   255 - 260   2004

    　More details

  • Metal Affinity-Immobilized Liposome Chromatography for Stress Mediated Separation of Biomolecules

    Nagami Hideto, Umakoshi Hiroshi, Kitaura Takeaki, Thompson III Gary Lee, Shimanouchi Toshinori, Kuboi Ryoichi

    Asian Pacific Confederation of Chemical Engineering congress program and abstracts   2004   991 - 991   2004

    　More details

    Language：English   Publisher：The Society of Chemical Engineers, Japan  

    Investigation and utilization of peptides and proteins depend upon their separation and purification, which may be accomplished with chromatographic methods. Among the possible methods, immobilized metal affinity chromatography (IMAC), first reported by Porath, is known as a useful and powerful tool of the separation and analysis of the peptides and proteins and currently becomes the most popular chromatographic technique. A metal-affinity immobilized liposome chromatography (MA-ILC) was newly developed as a new chromatographic technique to separate and analyze the protein. The MA-ILC was prepared from the immobilized liposome modified with the functional ligands. A N-hexadodecyl -imonodiacetic acid (HIDA) was then used as the functional ligand. The metal ion Cu(II) was first adsorbed by the coordination with the functional ligand-modified liposome, immobilized on a gel matrix before the analysis of the elution behaviors. Synthetic peptides ranging in size from 5 to 40 residues were used to evaluate the retention properties of MA-ILC. The retention properties using usual imidazole elution for MA-ILC at 303 K was compared with those for IMAC, which is a most popular separation method for proteins, and an immobilized liposome chromatography (ILC), which can separate and analyze the protein mainly by the hydrophobic interaction between the liposome and protein. The retention ability of peptide on MA-ILC has both the properties of IMAC and ILC; the capacity factor depends on both the number of His residue in peptide and the hydrophobicity of peptide. It is considered that the retention properties of IMAC could be related not only to the hydrophobic interaction between the peptide and liposome but also to the cluster formation of the ligands on the liposome surface.

    DOI： 10.11491/apcche.2004.0.991.0

    CiNii Article

    researchmap

  • Different Roles of Metal Ions Both in the Formation of Amyloid b-Fibri and Superoxide

    Nagami Hideto, Kishida Manabu, Umakoshi Hiroshi, Shimanouchi Toshinori, Kuboi Ryoichi

    Asian Pacific Confederation of Chemical Engineering congress program and abstracts   2004   498 - 498   2004

    　More details

    Language：English   Publisher：The Society of Chemical Engineers, Japan  

    The roles of metal ions both on the formation of fibril aggregation of amyloid-β-peptide (Aβ) and on the generation of superoxide by a metal-Aβ complex have been studied to clarify the relationship of both phenomena with the cause of Alzheimer's Disease (AD). Among the several metal ions, the addition of Zn(II) or of Cu(II) was found to increase the formation of Aβ fibril. Although Zn(II) promoted the Aβ fibril formation both at neutral and acidic pH levels, Cu(II) could induce the aggregation of Aβ only at acidic pH. In addition, hydrogen peroxide was generated at neutral pH in the absence of Aβ and Cu(II) beyond a stoichiometric amount of Cu(II) ion, suggesting the formation of a catalytic site that can react between Cu(II) and Cu(I). These results indicate that Zn(II) and Cu(II) at different pHs may each contribute to AD in different modes; the promotion of fibril aggregation (Zn(II) at every pH and Cu(II) at acidic pH) and the formation of superoxide (Cu(II) at neutral pH). The most characteristic aspect is the effect of pH on the promotion of aggregation and the formation of superoxide for the Cu(II)-Aβ system. The coordination structure of the Cu(II)-Aβ complex at neutral and acidic pHs was analyzed by using NMR spectroscopy, circular dichroism (CD), and ESR. The formation of a complex of histidine (His) residues and Cu(II) was found, and the coordination number of the His was suggested to be two at neutral pH and three at acidic pH. These results imply that the intramolecular coordination structure of the Aβ -Cu(II) complex at neutral pH could be converted to the intermolecular one by acidification. The pH variation thus led to a change in the complex structure of Cu(II)-Aβ. This finding suggests the important roles of pH to regulate two phenomena, i.e. the aggregation of Aβ (inhibition of superoxide formation) and the formation of superoxide from Cu(II)-Aβ complex.

    DOI： 10.11491/apcche.2004.0.498.0

    CiNii Article

    researchmap

  • Characterization of Stress-Response Behavior of SOD/CAT on Liposome under Heat/Oxidative Stresses

    Yoshimoto Noriko, Nagami Hideto, Umakoshi Hiroshi, Shimanouchi Toshinori, Kuboi Ryoichi

    Asian Pacific Confederation of Chemical Engineering congress program and abstracts   2004   481 - 481   2004

    　More details

    Language：English   Publisher：The Society of Chemical Engineers, Japan  

    A biological membrane is the frontier of the cells against the environmental reactive oxygen species (ROS) and is expected to play an important role in the antioxidant system corporately with antioxidant enzymes. The response behaviors of the antioxidant enzymes (superoxide dimutase (SOD) and catalase (CAT)) were investigated in the presence of artificial membrane, liposome, under the oxidative stress condition in order to obtain the fundamental information for the ROS scavenger system. The intracellular antioxidant enzymes, SOD and CAT, are known to make protective system against ROS. Although the SOD is known to catalyze the dismutation of ·O2- to H2O2. The activity of SOD was lost thoroughly in the presence of H2O2 at high concentration (>5mM). The SDS-PAGE analysis showed that the SOD was fragmented into several small peptides. SOD has two -helix loops, which introduce the substrate ·O2- to the activity center of SOD (Cu(II)). From the circular dichroism analysis of SOD in the presence of H2O2, the contents of α-helix in the SOD were found to decrease in corresponding with the inactivation of the SOD, suggesting that the conformation of the α-helix loops might be varied. However, the SOD was not inactivated in the presence of POPC liposomes while the contents of α-helix were decreased similarly in the case of that without liposome. Based on these results, the possibility to develop the ROS scavenger system using the SOD and CAT together with liposome was finally discussed.

    DOI： 10.11491/apcche.2004.0.481.0

    CiNii Article

    researchmap

  • 3I10-2 Coexistence effect of fatty acid-modified liposome on amyloid under stress condition

    LEE Bong-Kuk, NISHIMURA Daisuke, UMAKOSHI Hiroshi, SHIMANOCUHI Toshinori, KUBOI Ryoichi

    16   229 - 229   2004

    　More details

  • 3I10-1 Design and development of liposomal membrane : Application for monitoring of aqueous stressors

    SASAKI Masashi, LEE Bon-Kuk, SHIMANOUCHI Toshinori, MORITA Seiichi, KUBOI Ryoichi

    16   229 - 229   2004

    　More details

  • 固定化リポリームクロストグラフィーによる生理活性物質の分離・分析 Invited Reviewed

    ぶんせき   11   636 - 642   2003

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    researchmap

  • Characterization of the surface properties of chitosanase under heat stress condition using aqueous two-phase systems and an immobilized-liposome sensor system

    HS Jung, H Umakoshi, SY Son, T Shimanouchi, R Kuboi

    SOLVENT EXTRACTION RESEARCH AND DEVELOPMENT-JAPAN   10 ( 10 )   123 - 132   2003

    　More details

    Language：English  

    Web of Science

    researchmap

  • Development of Liposomal Artificial SOD controlled by Oxidative Stress

    Nagami Hideto, Kitaura Takenori, Shimanouchi Toshinori, Umakoshi Hiroshi, Kuboi Ryoichi

    15   215 - 215   2003

    　More details

  • 医薬品製造における晶析技術 タンパク質の構造異常化によるストレス誘導型アミロイドーシス

    島内寿徳, 馬越大, 久保井亮一

    分離技術   32 ( 6 )   347 - 351   2002.11

    　More details

  • タンパク質の構造異常・アミロイドーシスとそのセンシング Invited

    島内 寿徳, 佐々木 勝司, 久保井 亮一

    ケミカルエンジニヤリング   47   748 - 751   2002

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    researchmap

  • ストレス応答型バイオプロセスのためのストレスセンサの開発 Invited

    鄭 浩燮, 島内 寿徳, 馬越 大, 久保井 亮一, 金 廣, 櫻井 芳昭, 夏川 一輝

    ケミカルエンジニヤリング   47   752 - 755   2002

    　More details

    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)  

    researchmap

  • Eraluation of Interaction between Liposome Membranes Induced by Stimuli Reponsire Polymers and Proteins

    Journal of Bioscience and Bioengineering   93(5), 498-501/,   2002

    　More details

  • Selective separation process of proteins based on the heat stress-induced translocation across phospholipid membranes

    UMAKOSHI Hiroshi, SHIMANOUCHI Toshinori, KUBOI Ryoichi

    J. Chromatogr. B.   711 ( 1 )   111 - 116   1998.6

    　More details

▼display all

Presentations

▼display all

Industrial property rights

▼display all

Awards

  • 研究助成

    2020.4   八雲環境科学研究財団   環境低負荷な還元剤フリー金属ナノ粒子 形成法とその応用

    島内 寿徳

    　More details

  • 研究助成

    2016.8   八雲環境科学研究財団   金属無機塩と脂質膜からなるハイブリッド触媒による環境低負荷型反応プロセスの開発

    島内 寿徳

    　More details

  • 岡山工学振興会科学技術賞

    2015.7   岡山工学振興会   水晶振動子を活用するアルツハイマー病治療技術への展開

    島内 寿徳

    　More details

  • 研究助成

    2012.12   大川情報通信基金   生体膜異常化の解析アルゴリズムの構築

    島内 寿徳

    　More details

  • Young Scientist Award of Osaka University

    2011.11   Osaka University  

    SHIMANOUCHI Toshinori

    　More details

  • Young Scientist Award of The Membrane Society of Japan

    2011.5  

    SHIMANOUCHI Toshinori

    　More details

  • 6th Annual Report 2005-2006

    2006  

    　More details

  • 第六回 大阪大学論文百選 (2005年度)

    2006  

    　More details

  • 第五回 大阪大学論文百選 (2004年度)

    2005  

    　More details

  • Outstanding Paper Award in APCChE2004 (SCEJ) (Oct.,2004, Kita-Kyushu)

    2004  

    　More details

  • Outstanding Paper Award in APCChE2004 (SCEJ) (Oct.,2004, Kita-Kyushu)

    2004  

    　More details

▼display all

Research Projects

  • バイオ分離材料における表面汚染抑制と生体分子修復の両立の高度化に関する研究

    Grant number：24K01237  2024.04 - 2027.03

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    島内 寿徳

    　 More details

    Grant amount：\17810000 （ Direct expense: \13700000 、 Indirect expense：\4110000 ）

    researchmap

  • Basic technology of lipid membrane immunosensor for detection of pathogenic protein in blood contributing to ultra-early diagnosis of dementia

    Grant number：23K17476  2023.06 - 2026.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Pioneering)

    野田 実, 山門 穂高, 澤村, 正典, 島内 寿徳, 寒川, 雅之, 福澤, 理行, WERNER Frederik

    　 More details

    Authorship：Coinvestigator(s) 

    Grant amount：\25870000 （ Direct expense: \19900000 、 Indirect expense：\5970000 ）

    researchmap

  • 表面電位制御ベシクルテンプレート法によるメッシュ状中空シリカ粒子の調製

    Grant number：22K04820  2022.04 - 2025.03

    学術振興会  文部科学省科研費  基盤研究(C)

    林 啓太, 中村 秀美, 島内, 寿徳, 亀井 稔之, 石井, 治之, 岩崎 智之

    　 More details

    Authorship：Coinvestigator(s) 

    Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）

    本年度は主にシリカ粒子のテンプレートとなるベシクルの特性解析と，このテンプレートを用いたメッシュ状中空シリカ粒子の調製に関して検討を行った．研究当初はdidodecyldimethylammonium bromide (DDAB)とsodium dodecyl sulfate (SDS)から構成されるDDAB/SDSベシクルを用いて検討を行う予定であった．しかし，DDAB/SDSベシクルは安定性が低く，本研究で行った条件では目的とする粒子が得られなかった．そのため，カチオン脂質として1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)を用い，1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)，cholesterol (Chol)と混合してDOTAP/DSPC/Cholリポソームをテンプレートとした．蛍光プローブを用いた検討でDOTAP/DSPC/CholリポソームはDOTAP-rich相とDSPC-rich相に相分離することが明らかとなった．また，coumarinを用いた検討で，DOTAP-rich相界面は周囲の環境よりも塩基性であることが明らかとなった．このDOTAP/DSPC/Cholリポソームにtetraethyl orthosilicate (TEOS)を添加したところ，界面pHの違いによってTEOSの重合はDOTAP-rich相において選択的に進行することが明らかとなった．つまり，DOTAP/DSPC/Cholリポソームを用いることで，特定の部分のみがシリカ膜に覆われたメッシュ状中空シリカ粒子の調製に成功した．今後，このメッシュ状中空シリカ粒子にβ-galactosidaseを内包してタンパク質キャリアとして応用可能であるか議論する．

    researchmap

  • Development of new bioseparation material aiming at both suppression of surface contamination and repair of biomolecules

    Grant number：21H01692  2021.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    島内 寿徳

    　 More details

    Grant amount：\17290000 （ Direct expense: \13300000 、 Indirect expense：\3990000 ）

    本年度の研究実施計画に対応した結果を以下において個別に述べる。
    （１）モデル細胞膜の作成…ポリビニルピロリドンやポリメチルメアクリレートなどにより高分子支持膜を作成した。また、リン脂質と糖鎖脂質の混合脂質系を作成した。（２）リン脂質ポリマーの準備…高分子鎖長をn = 10～100まで変化させたものを準備した。（３）上記膜材料の物性評価…蛍光プローブの運動性の高さを偏向解消法で定量化し、極性環境の評価も行った。二重染色法により、混合脂質膜系の相分離性などを観察できるようになった。（４）動的ナノ空間分布の評価…原子間力顕微鏡を用いて膜内部に存在する動的構造を可視化した。さらに膜弾性係数を評価し、水和構造が強固なほど弾性が弱くなることが示唆された。（５）リン脂質ポリマー膜表面へのタンパク質吸着過程の検討…原子間力顕微鏡を用いて膜材料表面の付着力測定を行い、タンパク質の表面物性を用いて付着力を補正して吸着量を推定する補正関数を決定できた。（６）タンパク質の成長相モニタリング…まず蛍光標識タンパク質を作成した。膜界面でのアミロイドβ（Aβ）と高分子の絡み合いによる空間的制限がAβの並進拡散を抑制し、結果としてアミロイド核形成に影響を与えることが示された。
    <BR>
    さらに、（３）と（６）を踏まえると、タンパク質が平面膜上の特定の領域に集中して吸着されやすいことが判明した。この現象が各成長相の成長ダイナミクスに関連していることが示唆された。さらに、（１）と（６）より、膜上の並進拡散特性について、分子量と構造状態の双方に依存性があることが見いだされた。それゆえ、成長相の選択は界面上での並進拡散過程に関連するという予想は外れていないと考えられる。

    researchmap

  • Fundamental study on bioelectronic chip for diagnosis of pathologic conditions based on specific and ultrahighly sensitive detection of prion-like protein

    Grant number：20H00663  2020.04 - 2024.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    野田 実, 山門 穂高, 澤村 正典, 島内 寿徳, 寒川 雅之, 福澤 理行

    　 More details

    Grant amount：\44980000 （ Direct expense: \34600000 、 Indirect expense：\10380000 ）

    令和３年度はⅠ．センサ検出能力の生化学的側面として以下、検出分子技術手法が具体的進展した。
    １．aSyn凝集体の検出ではsandwich ELISA法にてpg/mlオーダーの検出系を確立し、髄液・血清においても交雑物質の影響を受けず標準物質と同様の感度を確認した。RT-QUICでも1pg/ml以下の標準物質の検出が可能とし、ELISAと組合せ脳homogenateからパーキンソン病、多系統萎縮症特異的なaSyn凝集体の検出を確認した。２．①脂質種を最適化、②機能性分子による脂質膜修飾添加双方として、相分離性脂質混合系や糖鎖脂質の混合系がaSynのモデル系としてのAβに対する検出感度を増強しこの脂質組成をaSynモノマーに応用した結果、aSyn凝集体形成過程への大きな干渉を確認できた。
    Ⅱ．集積アレイセンサ化では各要素技術が順調に進展した。１．マイクロ流路構造では、新規マイクロ溶液供給システムを構築し、測定溶液供給時におけるカンチレバーセンサの基本検出動作を確認し、出力ノイズ・変動は従来単体液滴保持構造センサでの測定前変動と同等だった。２．①カンチレバーセンサでは、1)ピエゾ抵抗検出部応力集中：1桁弱の感度向上、2)溶液中塩濃度の最適化：約５倍の感度向上、3)PD患者血清測定にて1),2)による数倍の識別性向上を確認した。QCMで上記検証を行いPD患者、非患者、健常者を含めサンプル数約５での再現性、十分な識別性を確認した。②IS-FETでは、ゲート検出部に特化したMOSダイオード自体のアレイ化使用を検討した。
    ③LSPRを含めてⅢ．アレイセンサ信号情報処理ではデータ収集性を最優先しており、吸収スペクトルの二次元分布を手動走査測定可能なパイロットシステムを構築してLSPR吸光度測定に成功し、LSPRチップへの適用性を確認した。

    researchmap

  • マイクロ流体システムによるアミロイドーシス指向型バイオ機能性ナノカプセルの設計

    2020.04 - 2022.03

    日本学術振興会  二国間交流事業  共同研究（日本-韓国）

    　 More details

    Authorship：Principal investigator 

    researchmap

  • A construction of new biosensor technology enabling highly sensitive detection of alpha-synuclein fibril originated from Parkinson's disease patient

    Grant number：19K22964  2019.06 - 2022.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory)  Grant-in-Aid for Challenging Research (Exploratory)

    Noda Minoru

    　 More details

    Grant amount：\6370000 （ Direct expense: \4900000 、 Indirect expense：\1470000 ）

    In this research, the detectivity of aggregated alpha-Syunuclein (aSyn) as a causative agent of Parkinson Disease (PD) was markedly improved by newly developed approaches and techniques. Starting from the aspects of phospholipid membrane, especially, 1) Confirmation on high-sensitivity for the aggregated aSyn down to 10 pg/ml by combination of the interaction with the phospholipid membrane and the self-templating phenomena of aSyn. Improved sensitivities; 2) by concentrating mechanical stress on piezoresistance part of cantilever sensor itself (increased by about an order), 3) by optimizing the salt concentration of target solution (increased by 5 times). Finally, 4) by using the developed biosensor technologies, the serums of PD patients were effectively discriminated from those from non-patients.

    researchmap

  • Mathematical analysis of the characteristic properties of nano-machines in a blood vessel

    Grant number：16KT0133  2016.07 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

    Obuse Kiori

    　 More details

    Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）

    We have performed numerical simulations of the dynamics of nanomachines in 3D Navier-Stokes flow in blood-vessel-like tube. It was suggested that the ratio of the representative length of nanomachines and the width of the holes on the boundary of the blood-vessel-like tube is important to control the probability of nanomachines’reaching the target cells outside the tube.
    We have also considered simple mathematical models to discuss the above situation. The dynamics of a nanoparticle in 2D Stokes shear flow in a semi‐infinite plane with a hole and in a 2D tube with boundaries where nonslip and slip boundary conditions are periodically considered were investigated by utilising complex analysis and numerical calculations. Here again, it was suggested that the ratio of the particle radius and the width of the hole/interval where slip boundary condition is considered are important to control the dynamics of the nanoparticle.

    researchmap

  • Fabrication and development of biosensor to detect aggregation of amyloid-beta oligomer

    Grant number：16K14254  2016.04 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Noda Minoru

    　 More details

    Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）

    Liposome biosensors are developed to detect dynamics of aggregation and fibrillization of amyloid-beta oligomer. Those sensors are expected to realize early and simple diagnosis and evaluation of progress in pathological change of Alzheimer Disease that expresses aggregation and accumulation of abnormal protein. In this research, both sensor device and biosensing phospholipid of liposome are investigated and developed as follows: I. Construction of the sensor device, II. Improvement in sensitivity of the sensor, and III. Comparison with ELISA result. A micro-TAS chip comprising of liposome cantilever sensor and microfluidic channels was fabricated. Consequently, dynamic aggregation and fibrillization of amyloid-beta related to its oligomer was selectively detected in human serum. Also, a high sensitivity was estimated that can detect less than 1 nM by excellent selection of phospholipid species, techniques of low-noise electronic circuit and precise temperature control of substrate.

    researchmap

  • Membrane-on-Membrane ~Creation of Hierarchical Self-Organizing Materials~

    Grant number：26249116  2014.04 - 2019.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    Umakoshi Hiroshi, Ishigami Takaaki, Iwasaki Fumihiko, Hirose Masanori, Taguchi Shogo, Watanabe Nozomi

    　 More details

    Grant amount：\40170000 （ Direct expense: \30900000 、 Indirect expense：\9270000 ）

    In this project, a novel membranous devise (material) was developed. Membrane-on-Membrane (MoM) was hierarchically composed by self-assembled membranes. Liposome was selected as core unit of MoM, because it showed unique functions such as recognition of L-amino acid, promoting organic reaction in water, and molecular orientation of chlorophyll. In addition, the methodologies, multiple-fluorescent probe analyses, membrane surface-enhanced Raman spectroscopy, dielectric dispersion (relaxation) spectroscopy, were developed to characterize the physicochemical properties of membranes (in micro- and mesoscale). As an example of our achievements, the “ordered” membrane property plays a crucial role to improve selectivity in chiral recognition of amino acid. When the liposome possessing ordered membrane property was applied to MoM device (for example, liposome-immobilized polyacrylamide hydrogel system), the chiral recognition ability could be maintained.

    researchmap

  • Liposome Physical Sensors Oriented to Label-free Integrated Chip for Early Diagnosis of Diseases Originated from Amyloid-beta Abnormality

    Grant number：26630157  2014.04 - 2016.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    Minoru Noda, SHIMANOUCHI Toshinori, MATSUOKA Teruyuki, YAMASHITA Kaoru, UMAKOSHI Hiroshi, NARIMOTO Jin

    　 More details

    Grant amount：\4030000 （ Direct expense: \3100000 、 Indirect expense：\930000 ）

    We have developed a new biosensing system composed of arrayed cell structure for dielectric dispersion analysis (DDA) of interaction with phospholipid membrane of liposome in order to enable to use plural different phospholipids as sensing molecule, as similar to cell membrane, and to measure simultaneously plural different target biomolecules such as proteins with different conditions. When measuring with normal human serum, we have successfully observed phenomena relating to fibrillization and/or aggregation of Aβ(1-40) with interaction of the liposomes by the DDA, also confirmed by a different sensing of cantilever sensor. Finally, we have detected 1 microM Aβ(1-40) by the DDA method, implying that the concentration in Alzheimer disease patient (20-500 nM) could be measured by an order of improvement.

    researchmap

  • 金属無機塩と脂質からなる新規ハイブリッドナノ触媒の調製とバイオPET前駆体合成反応への応用

    Grant number：14541900  2014 - 2015

    科学技術振興機構  産学が連携した研究開発成果の展開/研究成果展開事業/研究成果最適展開支援プログラム(A-STEP)/探索タイプ

    島内 寿徳

    　 More details

    ポリエチレンテレフタラートの代替物質である2,5-フランジカルボン酸(FDCA)の生産プロセスのための触媒開発を対象とした．金属無機塩型触媒と脂質構造体とを複合化して得た触媒をハイブリッドナノ触媒と呼び，FDCA合成を試みた結果，最大74%の収率を得た．特筆すべき点として，既往の方法と比較し，より低温かつ非NaOH系でのFDCA合成を達成した点である．今回検証した限りでは，ゲル担体にリポソームを共有結合により固定化し，金属触媒を担持させる構造が繰り返し使用と長期保存性に優れ，カラム操作に展開できることを実証した．加えて，安価な界面活性剤でハイブリッドナノ触媒を作成できることも見出した．

    researchmap

  • Desgin of Biointerfaces with Protein Refolding Property, Based on Amyloid Fibril Formation

    Grant number：24686086  2012.04 - 2015.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A)  Grant-in-Aid for Young Scientists (A)

    SHIMANOUCHI Toshinori

    　 More details

    Grant amount：\27170000 （ Direct expense: \20900000 、 Indirect expense：\6270000 ）

    In this study, we developed the noveland medical bio-interfaces with protein refolding property, based on the amyloid fibril formation. We used the variety of phospholipids, detergents, and polymers to investigate their kinetic interfacial properties such as fluidity and interfacial energy. Furthermore, the kinetic parameters including the nucleation time and elongation rate constant for the fibril formation were evaluated and its mechanistic detailes was discussed, taking into consideration of influence of the prepared interfaces. Consequently, it was suggested that the constituent of interfaces should require the molecular fluidity within the interface enough to allow the orientation of proteins into the interior of interfaces.

    researchmap

  • Developmentofcontrol for amyloid toxicity by novel Screening system

    Grant number：23656525  2011 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research  Grant-in-Aid for Challenging Exploratory Research

    SHIMANOUCHI Toshinori

    　 More details

    Grant amount：\3770000 （ Direct expense: \2900000 、 Indirect expense：\870000 ）

    Amyloid fibrils is generally propagated on biomembranes to induce the cell toxicity. Meanwhile, there is no methodology to stop the aforesaid event. In this study, we challenged the development of toxicity control of amyloid fibrils using liposomes. It has been demonstrated that liposome library could give (i) the adequate liposome with lipid composition advantageous for a control of toxicity of amyloid fibrils and (ii) LIPOzyme with the function to promote the inhibitory of fibril formation or disaggregatiojn of fibrils. Those results have implied a possibility on the development of detoxic process of amyloid fibrils by using liposomes.

    researchmap

  • 脂質分子を活用するタンパク質精製のための省エネ型晶析モジュールの開発

    Grant number：11102038  2011

    科学技術振興機構  産学が連携した研究開発成果の展開/研究成果展開事業/研究成果最適展開支援プログラム(A-STEP)/探索タイプ

    島内 寿徳

    　 More details

    本課題では、タンパク質の結晶(アミロイドを含む)が得られ、その結晶形態(多形)の制御が可能な晶析膜モジュールを開発することを目標とした。モデルタンパク質としてアミロイドβペプチド(Aβ)を用いると、リポソームによる結晶化(アミロイド形成)とその形態制御も可能である事が分かった。次に、非対称孔構造を有する透析膜モジュールにリポソームを充填したものを晶析モジュールとして使用した結果。Aβアミロイドの高回収率(～80%)を達成した。しかし、膜モジュール環境が結晶成長挙動に影響を及ぼすため、形態制御は現時点では困難である事が明らかになった。今後はモジュール環境の影響を低減するため、リポソームを高濃度条件でゲルマトリックスに包埋するための技術開発を展開したい。

    researchmap

  • 光学分割LIPOzymeを用いたキラル分離膜モジュールの開発

    Grant number：22656177  2010 - 2012

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    馬越 大, 久保井 亮一, 島内 寿徳

    　 More details

    Grant amount：\2170000 （ Direct expense: \1900000 、 Indirect expense：\270000 ）

    キラル分離法あるいは(化学的処理酵素的処理を伴う)不斉合成法は,医薬品製造プロセスの経済性・操作性・環境負荷を決定付ける重要なキー単位操作である.光学異性体を高度分離するために,キラル分離ならびに不斉合成のコア材料として,リボソーム,ならびに,不斉合成LIPOzymeを安定に固定化した膜モジュールを調製する.網羅的な解析データに基づいて,キラル認識の原理に迫り,同時に,大規模分離に耐えられる分離膜としての可能性を探る.初年度では,リボソームのキラル分離データベース:リボソームのキラル分離能力の系統的解析により基礎データベースを拡充することを目的とした
    まず,自然界に存在するL体の脂質から成るリボソーム((L)-リボソーム,と表記)を用いて,L体ならびにD体のアミノ酸のキラル分離能力を検討した.その結果,L-アミノ酸は(L)-リボソームに吸着したが,D-アミノ酸は吸着しなかった.特に,L-トリプトファンは97%吸着したが,D-トリプトファンは0%であった.さらに,L-/D-トリプトファン等モル混合溶液(ラセミ体)の光学分割にも成功した.アミノ酸吸着機構を検討した結果,静電的/疎水的相互作用,水素結合,ならびに不正炭素の配置が鍵であることが示唆された。また,吸着アミノ酸は脂質膜表面を流動化すると脱離することが確認され,分離プロセスとしての応用も可能であることが分かった.本萌芽技術は特許出願している
    2年目以降,不斉合成LIPOzyme : LIPOzyme触媒との組合せによるエナンチオ選択的な化学変換(酸化・還元・加水分解ほか)手法に関する基礎的なデータを集積する.さらに,3年目では,光学分割LIPOzyme膜モジュール:既存の独自技術であるリボソーム固定化膜モジュールを用いて,モジュール内部に上記LIPOzymeを固定化し,モジュール性能を検証する予定である

    researchmap

  • Studies on development and stabilization of intact liposome biosensor technology for Si-integrated structure

    Grant number：22360144  2010 - 2012

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    NODA Minoru, SHIMANOUCHI Toshinori, YAMASHITA Kaoru, FUKUZAWA Masayuki, SOHGAWA Masayuki, KUBOI Ryouich, UMAKOSHI Hiroshi, OKUYAMA Masanori

    　 More details

    Grant amount：\18980000 （ Direct expense: \14600000 、 Indirect expense：\4380000 ）

    In order to improve and stabilize the precision and performance of liposome biosensor and its sensing technologies, a series of technical considerations and resultant improvements have been done on the sensor as a key component of near future Si-integrated microsensor system. The technical developments are started from immobilization of minute droplet of liposome suspension and intact supramolecule structure. Moreover, new biosensing systems of liposome impedance biosensor and fluorescence array sensor are developed, based on electronics techniques. Finally, the sensitivities and performance of both leakage current sensor and cantilever strain sensor are improved because a resultant quantitative capability of immobilization of minute liposome droplet on the sensor becomes improved. We also note that the impedance sensor can detect the interaction between the liposome and target protein with a 100 nL order. And that the fluorescence array sensor system can discriminate different target biomolecules.

    researchmap

  • Study on Peptide Display on Liposome Membranes for Disaggregation of Amyloid Fibrils

    Grant number：21246121  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    KUBOI Ryoichi, SHIMANOUCHI Toshinori, HIROSHI Umakoshi, YOSHIMOTO Makoto, SHIOMORI Kouichiro, GOTO Yuji

    　 More details

    Grant amount：\45370000 （ Direct expense: \34900000 、 Indirect expense：\10470000 ）

    We systematically investigated the polymorphism of amyloid Aβ/ Cu fibrils and their catalytic oxidation activity using the liposome as a model biomembrane. It was clarified that the oxidized surface of liposome could affect the catalytic oxidation activity of amyloids as well as their morphology. It was revealed that the experiments using peptide fragments-displayed liposomes could contribute to the better understanding on the regulatory mechanism of catalytic oxidation activity of Aβ/ Cu. Besides, we developed the novel loading method of liposomes into the module. Those results suggested that a recognition system of abnormal/ damaged biomembranes for their repairmen could be in principle developed, from those results.

    researchmap

  • Densign and Development of Stress Responsive LIPOzyme Reactor Based on Re-functionalization of Junk Peptides

    Grant number：20360350  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    UMAKOSHI Hiroshi, KUBOI Ryoichi, SHIMANOUCHI Toshinori, SHIOMORI Koichiro, NAKAMURA Hidemi, MORITA Seiichi

    　 More details

    Grant amount：\18720000 （ Direct expense: \14400000 、 Indirect expense：\4320000 ）

    It is demonstrated that the function of LIPOzyme (Liposome+Enzyme) could be induced by the construction of catalytic sites on the liposome membrane as a model biomembrane. The LIPOzyme function could be classified by three categories : (i) electron transfer ; (ii) proton transfer ; (iii) nucleophilic/electrophilic reaction. The LIPOzyme function could be, herewith, controlled by the tuning of junk peptides, ligands or their metal complexes to achieve the desired function. Furthermore, the immobilization of LIPOzyme into the module was presented to develop the novel membrane module. This technique is a promising method to develop the reactor/separator based on the LIPOzyme function. Besides, the mapping of the physicochemical properties of junk peptides and the lipid composition could be performed to clarify the optimal condition for the desired functions of LIPOzyme, resulting in developing their database.

    researchmap

  • Study on crystallization and polymorphism of amyloidgenic proteins on biomembranes

    Grant number：20760539  2008 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    SHIMANOUCHI Toshinori, GOTO Yuji, NODA Minoru

    　 More details

    Grant amount：\4290000 （ Direct expense: \3300000 、 Indirect expense：\990000 ）

    Amyloid firbril formation is similar to a crystallization. The amyloid fibrils fragmented in advance has been reported to play a role for a seeds. The seeds showed the variety of their growth behavior in the presence of the model biomembranes (liposomes). The addition of oxidative stress could lead to the formation of radiated amyloid fibrils (spherulite) and as well as the oxidized liposome could. It is, therefore, suggested that the liposome membranes determined the polymorphism of the amyloid.

    researchmap

  • バイオメンブレン・クロマトグラフィーの創成

    Grant number：19656203  2007 - 2009

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    久保井 亮一, 馬越 大, 島内 寿徳, 森田 誠一

    　 More details

    Grant amount：\3300000 （ Direct expense: \3300000 ）

    「バイオメンブレン・クロマトグラフィー」を開発するために,最小分離基材となる「超機能性リポソーム(生体膜Mimics)」の調製を中心として,次の3段階に分けて研究を進めてきた:(第1段階)超機能性リポソームの調製ならびに機能評価;(第2段階)超機能性リポソームの固定化ならびに安定性評価;(第3段階)バイオメンブレン・クロマトグラフィーの基礎
    最終年度は,バイオメンブレン・クロマトグラフィーの基礎データ蓄積と,工学的な応用について検討した.特に,【高度分離】ならびに【反応分離】に主眼においた,下記の2つのケーススタディを対象として,基礎と応用を密接にリンクさせた.
    [ケーススタディ]
    (A)高度分離モード:Alzheimer症関連ペプチドの構造状態の解析
    (B)反応/分離モード:リポソームをコア材料とする臓器代替デバイス(リポソーム人工臓器)の開発
    Amyloid β-Peptideを始めとするアミロイド性タンパク質(ケーススタディ(A))や抗酸化酵素を始めとする機能性酵素(ケーススタディ(B))を対象として,ストレス負荷により分子認識モードを制御したバイオメンブレン・クロマトグラフィーを用いて網羅的に解析した.既存のクロマトグラフィー(イオン交換,アフィニティなど)で得られる情報と比較し,バイオメンブレン・クロマトグラフィーの特徴ならびにその利用方法を体系化した.

    researchmap

  • Studies on biosensor device technology based on immobilization of intact liposome on Si-integrated sensor structure

    Grant number：19360162  2007 - 2009

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)  Grant-in-Aid for Scientific Research (B)

    NODA Minoru, SHIMANOUCHI Toshinori, OKUYAMA Masanori, KUBOI Ryouichi, MURAKAMI Shuichi

    　 More details

    Grant amount：\18980000 （ Direct expense: \14600000 、 Indirect expense：\4380000 ）

    We have studied a series of biosensor device technologies based on immobilization of intact liposome on Si-integrated sensor structure. As a result, the immobilized liposome keeps its intact behavior more than 24hrs, meaning practically long time range for usual sensing. Based on the result, three type of liposome biosensor of microbolometer biothermochemical sensor, leakage current sensor and cantilever strain sensor are designed, fabricated and evaluated for detection of target proteins. Finally these sensors are confirmed to show their effective sensing performance.

    researchmap

  • ストレス負荷バイオメンブレンによる遺伝子制御に関する研究

    Grant number：19656220  2007 - 2008

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    馬越 大, 久保井 亮一, 島内 寿徳, 土戸 哲明

    　 More details

    Grant amount：\3300000 （ Direct expense: \3300000 ）

    本研究課題の目的は、Membrane(生体膜/モデル生体膜)のストレス応答機能を利用する新規な遺伝子制御技術の開発である。ここでは、以下の3項目に関して検討している。
    (1) In vitro転写・翻訳プロセスにおけるリポソームの役割
    (2) In vivo合成プロセスにおける生体膜の役割
    (3) In process生産系への応用
    本年度では、特に(2)と(3)について検討した。種々の膜特性(電荷密度、流動性、ドメイン形成度など)を有するリポソーム共存系において、緑色蛍光タンパク質(GFP)の発現効率を検討した結果、翻訳されたペプチドとリポソーム間の静電相互作用を適切に制御する必要性が示唆された。また、転写の際メッセンジャーRNA(mRNA)からの遺伝子発現効率を検討した結果、mRNA-リポソーム間静電相互作用が遺伝子干渉効果に影響を及ぼすことが見出された。さらに、特定の酸化ストレスを負荷すると、遺伝子干渉効果が緩和できることを発見した。したがって、ストレス負荷生体膜が遺伝子発現過程を制御することが可能であることが示唆された。さらに、項目(3)について、Streptmyces griseus株による酵素キトサナーゼの生産プロセスにリポソームを利用した結果、キトサナーゼの膜上への提示が可能であり、膜の水和特性に応じて、キトサナーゼ活性を制御できることが示された。
    以上より、リポソーム(モデル生体膜)による遺伝子発現過程ならびに菌体による目的生産物(タンパク質)の生産プロセスの制御技術の枠組みを提案することができたと考えられる。

    researchmap

  • ストレス応答型人工酵素リポソームの設計・開発

    Grant number：17656268  2005 - 2006

    日本学術振興会  科学研究費助成事業 萌芽研究  萌芽研究

    久保井 亮一, 馬越 大, 島内 寿徳, 吉本 誠, 森田 誠一

    　 More details

    Grant amount：\3400000 （ Direct expense: \3400000 ）

    本申請課題では,リポソーム界面を反応場として,環境条件の変動(ストレス)に応答して触媒活性を制御する新規な人工酵素の創成を目的とする.平成17年度は,環境の酸化ストレス状態を認識して活性を制御するための活性中心として,アミロイドβタンパク質やスーパーオキシドジスムダーゼ(SOD)を膜上に提示し,酵素様活性が発現することを示した.そこで,平成18年度は,ROS応答・制御型人工酵素リポソームの設計・開発を目的として,以下の2班にわけて検討を進めた.
    (a)人工SOD機能解析班:天然SODの活性中心を模倣した人工SODリポソームを設計・開発する.前年度に開発したPorphyrinやアミノ酸残基をベースとしたリガンドをリポソームに修飾する事により,リガンドの離合集散(クラスター形成)挙動とSOD活性とが相関することを見出した.したがって,リポソーム膜のストレス応答特性による活性制御の可能性が示唆された.(馬越,吉本,久保井)
    (b)リポソーム/センサ班:上記の機能性リガンドにより修飾した,あるいはその他の膜成分を変化させたリボソームを調製し,誘電分散解析法,あるいはリボソーム固定化QCM(水晶振動子)を用いて,そのドメイン形成挙動やタンパク質・ペプチドとの相互作用を解析した.その結果,温度変化などのストレス条件に応じてリガンドのクラスター形成挙動を制御することが可能であり,SOD活性を制御可能であることが示された.(島内,森田,久保井)
    上記の知見を総括して,当該研究期間において,リボソームのストレス応答特性に基づいて,活性中心としてのリガンドのクラスター形成挙動を制御することによりSOD活性を発現することが可能であることを示せた.さらに,人工酵素リボソームを設計・開発するための新規なアプローチ(Build-up型ならびにBreak-down型)を提案し,体系化の方針を明確にした.

    researchmap

  • 人工臓器への応用を指向した生体機能集積型素子(プロテオリポソーム)の設計・開発

    Grant number：16760635  2004 - 2005

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    島内 寿徳

    　 More details

    Grant amount：\2900000 （ Direct expense: \2900000 ）

    本研究課題では,プロテオリポソームを,従来の研究用ツールだけでなく人工臓器などに対して工業的に利用してくための基盤的知見を獲得することを目的としている.しかしながら,従来のプロテオリポソームの調製法,安定性,操作性には克服しなければならない問題点があるのも事実である.そこで,平成16年度では,(プロテオ)リポソームの特性解析に基づき,操作条件下での(プロテオ)リポソームの機能評価と担体への固定化が原理的に可能であることを見出した.平成17年度は,(プロテオ)リポソーム膜上に種々の酵素(断片)を提示することで当該機能をリポソームに付与することを目的とした.さらに,固定化リポソームカラムの薬物排出能を検討し,人工臓器への応用の可能性について基礎的検討を行った.
    検出用分子素子を封入したリポソームを用いたセンサシステムにより,熱,pH,酸化ストレス条件下におけるタンパク質・リポソームの特性/相互作用解析を統一的に進めることが出来ることを示した.この知見に基づき,脂質膜・(モデル)生体膜のストレス応答ダイナミクス((脂質)膜界面ダイナミクス)に立脚したリポソーム材料調製・機能発現・ストレス有効利用型プロセスの設計を目指した新領域「メンブレン・ストレスバイオテクノロジー」を提案している.例えば,酸化ストレス消去系酵素であるスーパーオキシドジスムターゼ(断片)をリポソーム膜上に提示し,酸化ストレス消去能をリポソームに付与することに成功した.さらに,高周波誘電分散解析(周波数範囲1M-30GHz)などの手法を用いて,膜の水和状態の変化,ならびに,変性タンパク質や膜タンパク質の脂質膜への導入過程をモニタリングし,(プロテオ)リポソーム調製への指針を得ている.プロテオリポソームの固定化条件を最適化して得られる固定化リポソームクロマトグラフィーは,長期間安定に使用可能であり,人工臓器の操作条件(37℃)での安定した薬物排出能を発揮することが確認された.

    researchmap

  • Development of Sensor System to Analyse and Diagnose the abnormality of Protein Conformation

    Grant number：15206089  2003 - 2005

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)  Grant-in-Aid for Scientific Research (A)

    KUBOI Ryoichi, TSUCHIDO Tetsuaki, GOTO Yuji, UMAKOSHI Hiroshi, YOSHIMOTO Makoto, SHIMANOUCHI Toshinori

    　 More details

    Grant amount：\43680000 （ Direct expense: \33600000 、 Indirect expense：\10080000 ）

    The goal of this research project is to establish the analytical method of dynamic interaction between the structurally abnormal protein and biomembrane under the stress condition, especially focusing on the local hydrophobicity (LH) or structural fluctuation. Amyloid beta peptide (Aβ) has been employed as a case study of the system to analyze and characterize the structural abnormality of various proteins. During past two years, we have developed the sensor system of the structural abnormality of protein and have established the database on the protein abnormality under the stress condition. In 2005, the method to judge the structural abnormality of proteins has been investigated based on the previous findings. Based on the database, the suitable conditions (stress condition and lipid compositions) to regenerate the conformational abnormality of protein under the stress condition on the liposome surface have been clarified, resulting that the microdomain-like structure of the membrane surface was found to play an important role on the conformational abnormality of proteins/peptides. It was furthermore found that the microdomain-like structure could suitably be controlled by the control of the stress conditions (heating, pH and ionic strength) and the modification of membrane components (alcohols, fatty acids, cholesterol). Especially in the case of the cholesterol-modified liposome, the Aβ-membrane interaction was found to be controlled on the membrane in the presence of metal ion, Cu. The Aβ-Cu complex furthermore induced the metalloenzyme-like function(oxidation of cholesterol and dopamine). The above potential functions of Aβ on the membrane was found to be closely related to the stability of hydrogen-bond of the main chain of the Aβ in the hydrophobic nano environment inside the liposome membrane. By using the membrane chip arraying various stressed-liposomes on the chip, it was found that we could assess the structural abnormality of the protein. The above findings on the structural abnormality of protein were summarized together with the physiological role of amyloid fibril formation of Aβ on the biomembrane.

    researchmap

  • タンパク質の構造異常に関わるストレス応答ダイナミクスの評価

    Grant number：14750637  2002 - 2003

    日本学術振興会  科学研究費助成事業 若手研究(B)  若手研究(B)

    島内 寿徳

    　 More details

    Grant amount：\2900000 （ Direct expense: \2900000 ）

    本申請課題では,次世代型ナノバイオチップによるタンパク質のストレス応答ダイナミクスの解析・構造異常性の機構解明を目指す.そのため,以下の項目に分けて検討した.
    1.リポソームのナノバイオチップへの応用
    リポソームの誘電分散解析を行ない,数10MHz付近に現われる誘電緩和がリン脂質分子の軸回転運動,ならびに脂質膜の流動性に対応することがわかった.この緩和特性とリポソームの膜特性((i)膜流動性,(ii)電荷密度,(iii)面・局所的疎水性)との間に対応関係を見出すことができた.さらに熱・pHなどのストレス条件下での誘電特性を評価し,リポソームのストレス応答特性データベース化を行なった.
    2.タンパク質のストレス応答の評価
    タンパク質をセンサ素子であるリポソームと共存させると,リポソームの緩和周波数の変化が認められた.リポソームの膜特性を表す緩和周波数の変化から,相互作用している各種タンパク質の変性/巻き戻り過程・多量体化・二次構造の変化の過程に関する情報をon-lineで得ることができた.また,1.で得たデータベースに基づき,電解質封入リポソームを固定化した電極を作成し,タンパク質との相互作用で誘導される電解質の漏出を電気化学的に計測することで,多変量解析によるパタン解析への展開の可能性も示す事ができた.タンパク質の構造状態を解析することができた.これらの手法を併用することで,れゆえ,生体膜上でのアミロイド性タンパク質の構造異常化に関するオンラインモニタリングの可能性を示す事ができた.

    researchmap

  • 生体機能膜倣型マイクロバイオチップの設計・開発とプロテオーム解析への応用

    Grant number：14655310  2002 - 2003

    日本学術振興会  科学研究費助成事業  萌芽研究

    久保井 亮一, 吉本 誠, 島内 寿徳, 馬越 大, 森田 誠一

    　 More details

    Grant amount：\2000000 （ Direct expense: \2000000 ）

    本申請課題では、生体素子(分子シャペロン・酵素など)・生体模倣素子(人工シャペロンなど)のストレス(刺激)応答特性に関する知見に基づいて,それらをモデル細胞(リポソーム・逆ミセルなど)の界面に複合化・集積化した『複合集積型ナノバイオファクトリー』を構築する事を目的とする.さらには,申請者らが検討を進めている,マイクロヒータアレイ作成技術,および,リポソーム固定化技術を利用する事により,複数のナノバイオファクトリーをアレイ化したマイクロバイオチップを作成し,プロテオーム解析ツールとしての可能性について検討する事を目的とする.平成15年度においては,以下の項目について検討してきた.
    1.リポソームを用いたマクロバイオチップの開発 リポソーム固定化技術を利用して,電極表面上に電解質封入リポソーム(センサ素子)を固定化した.また,変性タンパク質に伴う電解質漏出を電気化学的計測法に基づいて検出することに成功した.さらに検出値は脂質組成や高分子(キトサンなど)修飾に依存する事がわかった.以上の知見に基づいてストレス条件下における生体高分子-モデル細胞膜間相互作用ダイナミクスのオンライン計測が可能である事を示した.
    2.プロテオーム解析ツールとしての利用 電気化学的手法で得られた検出値を多変量解析によりパターン解析した結果,タンパク質の構造状態を分離・検出する事が可能であった.また,原理の異なるセンサ(導電性高分子膜や誘電分散解析法)と併用する事により,同様の結果を得られプロテオーム解析への応用の可能性が示された.
    以上の知見を総合し,モデル細胞膜を固定化したセンサ電極をプラットホームとしたマイクロバイオチップの構築するための指針を明らかにして.また,電気化学的計測法などと併用する事によりタンパク質のストレス応答挙動を高感度で検出可能であり,プロテオーム解析ツールとして利用が可能であることが示された.

    researchmap

▼display all

 

Class subject in charge

  • Academic Writing （2025academic year） Third semester  - 月7～8

  • Academic Writing （2025academic year） Fourth semester  - 月7～8

  • Academic Writing （2025academic year） Third semester  - 火5～6

  • Design of Chemical Process I （2025academic year） special  - その他

  • Low-carbon and Resource Circulation Process Engineering （2025academic year） Prophase  - 月3～4

  • Chemical Engineering 2A （2025academic year） 1st semester  - 金5～6

  • Chemical Engineering 2B （2025academic year） Second semester  - 金5～6

  • Chemical Engineering 2 （2025academic year） 1st and 2nd semester  - 金5～6

  • Synthetic Chemistry Experiment 2 （2025academic year） 1st semester  - 月5～8,木5～8

  • Applied Chemistry Experiment 1 （2025academic year） 1st semester  - 月5～8,木5～8

  • Seminar in Advanced Chemistry （2025academic year） Other  - その他

  • Material Process Experiment 2 （2025academic year） 1st semester  - 月5～8,木5～8

  • Materials Process Engineering 1 （2025academic year） Prophase  - その他

  • Materials Process Engineering 2 （2025academic year） Prophase  - その他

  • Materials and Reaction Process Engineering （2025academic year） Late  - 火1～2

  • Physical Chemistry 3 （2025academic year） Third semester  - 月3～4,木1～2

  • Physical Chemistry 3 （2025academic year） Third semester  - 月3～4,木1～2

  • Advanced Study （2025academic year） Other  - その他

  • Environmental Process Engineering （2025academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2025academic year） Other  - その他

  • Seminar in Environmental Process Engineering （2025academic year） Year-round  - その他

  • Biochemiacl Engineering （2025academic year） Late  - その他

  • Biointerface Engineering （2025academic year） Late  - その他

  • Academic Writing （2024academic year） Third semester  - 月7～8

  • Academic Writing （2024academic year） Fourth semester  - 月7～8

  • Academic Writing （2024academic year） Third semester  - 火5～6

  • Low-carbon and Resource Circulation Process Engineering （2024academic year） Prophase  - 月3～4

  • Separation Engineering Ⅱ （2024academic year） Second semester  - その他5～6

  • Chemical Engineering 2A （2024academic year） 1st semester  - 金5～6

  • Chemical Engineering 2B （2024academic year） Second semester  - 金5～6

  • Chemical Engineering 2 （2024academic year） 1st and 2nd semester  - 金5～6

  • Synthetic Chemistry Experiment 2 （2024academic year） 1st semester  - 月5～8,木5～8

  • Applied Chemistry Experiment 1 （2024academic year） 1st semester  - 月5～8,木5～8

  • Seminar in Advanced Chemistry （2024academic year） Other  - その他

  • Advanced Chemistry and Materials in Liberal Arts （2024academic year） special  - その他

  • Material Process Experiment 2 （2024academic year） 1st semester  - 月5～8,木5～8

  • Materials Process Engineering 1 （2024academic year） Prophase  - その他

  • Materials Process Engineering 2 （2024academic year） Prophase  - その他

  • Materials and Reaction Process Engineering （2024academic year） Late  - 火1～2

  • Physical Chemistry 3 （2024academic year） Third semester  - 月3～4,木1～2

  • Physical Chemistry 3 （2024academic year） Third semester  - 月3～4,木1～2

  • Advanced Study （2024academic year） Other  - その他

  • Environmental Process Engineering （2024academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2024academic year） Year-round  - その他

  • Basic Experiments in Analytical Chemistry （2024academic year） 1st-4th semester  - [第１学期]月5～8,木5～8, [第２学期]月5～8,木5～8, [第３学期]その他, [第４学期]月5～8

  • Experiments and Exercises in Environmental Chemistry C （2024academic year） 1-3 semesters  - その他

  • Biochemiacl Engineering （2024academic year） Late  - その他

  • Biointerface Engineering （2024academic year） Late  - その他

  • Academic Writing （2023academic year） Third semester  - 火5～6

  • Academic Writing （2023academic year） Fourth semester  - 月7～8

  • Academic Writing （2023academic year） Third semester  - 月7～8

  • Low-carbon and Resource Circulation Process Engineering （2023academic year） Prophase  - 月3～4

  • Process Design for Separation （2023academic year） Late  - その他

  • Separation Engineering Ⅱ （2023academic year） Third semester  - 金3～4

  • Separation Engineering I （2023academic year） Second semester  - 金5～6

  • Chemical Engineering 2A （2023academic year） 1st semester  - 金5～6

  • Chemical Engineering 2B （2023academic year） Second semester  - 金5～6

  • Chemical Engineering Ⅱ （2023academic year） 1st semester  - 金5～6

  • Chemical Engineering Ⅲ （2023academic year） Third semester  - 月1～2

  • Chemical Engineering 2 （2023academic year） 1st and 2nd semester  - 金5～6

  • Chemical Reaction Engineering I （2023academic year） 1st semester  - 火4,金2

  • Synthetic Chemistry Experiment 2 （2023academic year） 1st semester  - 月5～8,木5～8

  • Applied Chemistry Experiment 1 （2023academic year） 1st semester  - 月5～8,木5～8

  • Seminar in Advanced Chemistry （2023academic year） Other  - その他

  • Separation Engineering （2023academic year） Prophase  - その他

  • Advanced Chemistry and Materials in Liberal Arts （2023academic year） Third semester  - 水1～2

  • Material Process Experiment 2 （2023academic year） 1st semester  - 月5～8,木5～8

  • Materials Process Engineering 1 （2023academic year） Prophase  - その他

  • Materials Process Engineering 2 （2023academic year） Prophase  - その他

  • Materials and Reaction Process Engineering （2023academic year） Late  - 火1～2

  • Physical Chemistry 3 （2023academic year） Third semester  - 月3～4,木1～2

  • Physical Chemistry 3 （2023academic year） Third semester  - 月3～4,木1～2

  • Advanced Study （2023academic year） Other  - その他

  • Special Research （2023academic year） Year-round  - その他

  • Environmental Process Engineering （2023academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2023academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2023academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2023academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2023academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2023academic year） Year-round  - その他

  • Basic Experiments in Analytical Chemistry （2023academic year） 1st and 2nd semester  - 月5～8,木5～8

  • Experiments and Exercises in Environmental Chemistry C （2023academic year） 1-3 semesters  - その他

  • Biochemiacl Engineering （2023academic year） Late  - その他

  • Biointerface Engineering （2023academic year） Late  - その他

  • Phase Equilibria （2023academic year） Third semester  - 月3,木1

  • Electrochemistry II （2023academic year） Third semester  - 月4,木2

  • Process Systems Engineering （2022academic year） Second semester  - 火3～4

  • Academic Writing （2022academic year） Fourth semester  - 月7～8

  • Academic Writing （2022academic year） Third semester  - 火5～6

  • Academic Writing （2022academic year） Third semester  - 月7～8

  • Process Systems Engineering （2022academic year） Second semester  - 火3～4

  • Process Design for Separation （2022academic year） Late  - その他

  • Separation Engineering Ⅱ （2022academic year） Second semester  - 火5～6

  • Separation Engineering I （2022academic year） 1st semester  - 火5～6

  • Chemical Engineering Ⅱ （2022academic year） Second semester  - 木3～4

  • Chemical Engineering Ⅲ （2022academic year） Third semester  - 月1～2

  • Chemical Reaction Engineering I （2022academic year） Third semester  - 金1～2

  • Separation Engineering （2022academic year） Prophase  - 月5～6

  • Advanced Chemistry and Materials in Liberal Arts （2022academic year） 1st semester  - 木5～6

  • Advanced Chemistry and Materials in Liberal Arts （2022academic year） Third semester  - 水7～8

  • Physical Chemistry 3 （2022academic year） Third semester  - 月3～4,木1～2

  • Physical Chemistry 3 （2022academic year） Third semester  - 月3～4,木1～2

  • Mathematics for Material Chemistry （2022academic year） Second semester  - 木1～2

  • Special Research （2022academic year） Year-round  - その他

  • Seminar in Environmental Process Engineering （2022academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2022academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2022academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2022academic year） Prophase  - その他

  • Basic Experiments in Analytical Chemistry （2022academic year） 1st and 2nd semester  - 月5～8,木5～8

  • Experiments and Exercises in Environmental Chemistry C （2022academic year） 3rd and 4th semester  - 金5～7

  • Academic Writing （2021academic year） Third semester  - 月7～8

  • Academic Writing （2021academic year） Fourth semester  - 月7～8

  • Academic Writing （2021academic year） Third semester  - 火5～6

  • Process Design for Separation （2021academic year） Late  - その他

  • Separation Engineering （2021academic year） 1st and 2nd semester  - 火5～6

  • Separation Engineering Ⅱ （2021academic year） Second semester  - 火5～6

  • Separation Engineering I （2021academic year） 1st semester  - 火5～6

  • Chemical Engineering Ⅱ （2021academic year） Second semester  - 木3～4

  • Chemical Engineering Ⅲ （2021academic year） Third semester  - 月3～4

  • Chemical Engineering B （2021academic year） 2nd and 3rd semester  - [第２学期]木3～4, [第３学期]月3～4

  • Separation Engineering （2021academic year） Prophase  - 月5～6

  • Advanced Chemistry and Materials in Liberal Arts （2021academic year） 1st semester  - 木5～6

  • Special Research （2021academic year） Year-round  - その他

  • Seminar in Environmental Process Engineering （2021academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2021academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2021academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2021academic year） Prophase  - その他

  • Basic Experiments in Analytical Chemistry （2021academic year） 1st and 2nd semester  - 月7～9,木7～9

  • Basic Experiments in Analytical Chemistry （2021academic year） 1st and 2nd semester  - 月7～9,木7～9

  • Experiments and Exercises in Environmental Chemistry C （2021academic year） 3rd and 4th semester  - [第３学期]金7～9, [第４学期]金5～7

  • Experiments in Environmental Chemistry Ⅲ （2021academic year） 3rd and 4th semester  - [第３学期]金7～9, [第４学期]金5～7

  • Process Systems Engineering （2020academic year） Second semester  - 火1,火2

  • Academic Writing （2020academic year） Third semester  - 月7,月8

  • Academic Writing （2020academic year） Fourth semester  - 月7,月8

  • Process Systems Engineering （2020academic year） Second semester  - 火1,火2

  • Process Design for Separation （2020academic year） Late  - その他

  • Separation Engineering （2020academic year） 1st and 2nd semester  - 火4,火5

  • Separation Engineering Ⅱ （2020academic year） Second semester  - 火4,火5

  • Separation Engineering I （2020academic year） 1st semester  - 火4,火5

  • Chemical Engineering Ⅱ （2020academic year） Second semester  - 木1,木2

  • Chemical Engineering Ⅲ （2020academic year） Third semester  - 火1,火2

  • Chemical Engineering B （2020academic year） 2nd and 3rd semester  - [第２学期]木1,木2, [第３学期]火1,火2

  • Separation Engineering （2020academic year） Prophase  - 月4,月5

  • Advanced Chemistry and Materials in Liberal Arts （2020academic year） 1st semester  - 木6,木7

  • Special Research （2020academic year） Year-round  - その他

  • Seminar in Environmental Process Engineering （2020academic year） Prophase  - その他

  • Seminar in Environmental Process Engineering （2020academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2020academic year） Late  - その他

  • Seminar in Environmental Process Engineering （2020academic year） Prophase  - その他

  • Basic Experiments in Analytical Chemistry （2020academic year） 1st and 2nd semester  - 月6,月7,月8,木6,木7,木8

  • Basic Experiments in Analytical Chemistry （2020academic year） 1st and 2nd semester  - 月6,月7,月8,木6,木7,木8

  • Experiments and Exercises in Environmental Chemistry C （2020academic year） 3rd and 4th semester  - 金6,金7,金8

  • Experiments in Environmental Chemistry Ⅲ （2020academic year） 3rd and 4th semester  - 金6,金7,金8

  • Introduction to Environmental Chemistry and Materials （2020academic year） 1st and 2nd semester  - 金6

  • Introduction to Environmental Chemistry and Materials I （2020academic year） 1st semester  - 金6

  • Introduction to Environmental Chemistry and Materials II （2020academic year） Second semester  - 金6

▼display all