岡山大学シーズ・ニーズ創出強化イノベーション対話促進プログラム2013　→ Bound for the Future

平成25年度文部科学省「大学等シーズ・ニーズ創出強化支援事業（イノベーション対話促進プログラム）」採択課題において、SDGs推進研究大学である岡山大学が取り組んでいるイノベーション促進のための3つの対話コアである「①光技術と生命科学融合、②産官学連携強化、③未来志向型異分野ネットワーク構築」について紹介。さらに事業後も「地域中核・特色ある研究大学：岡山大学」からの未来を拓く教育研究・社会貢献活動などについて随時ご紹介。　since2013~2024, "All rights reserved" , OKAYAMA University, JAPAN.

2019年3月31日日曜日

【情報発信】「SDGsスタートアップが牽引する“誰一人取り残さない”世界の実現」について佐藤法仁URA・副理事が講演

2015年に国連で採択された「持続可能な開発目標（Sustainable Development Goals ; SDGs）」は、17のゴールと169のターゲットなどがあり、「誰一人取り残さない」世界の実現を目指しています。岡山大学では全国の大学に先駆けて、槇野博史学長が掲げた「槇野ビジョン」のもと、全学を挙げて地域などのさまざまなステークホルダーらと共にSDGsを強力に推進しています。

今回、SDGs達成のために必須とも言えるビジネスのあり方について、既存企業だけではなく、現代の潮流のもと育った新進気鋭のスタートアップらの挑戦について語り、SDGs達成を推進するイベントが1月28日、都内で開催され岡山大学東京オフィス駐在で本学SDGs推進企画会議委員である佐藤法仁URA・副理事（企画・評価・総務担当）[内閣府科学技術政策フェロー]が登壇しました。

佐藤法仁URA・副理事は、「SDGsスタートアップが牽引する“誰一人取り残さない”世界の実現～価値ある発明でイノベーションを創造できるビジネスモデルをいかに創出するか～」と題して、「SDGsスタートアップ」という新しい枠組みのもと、発明とイノベーションを区別しつつ、それを橋渡し、社会に実装化するビジネスモデルのあり方について、特にSDGs達成のためのターゲットベースをもとにした点について具体例を挙げて紹介しました。

佐藤法仁URA・副理事は講演において、特に副題である「価値ある発明でイノベーションを創造できるビジネスモデルをいかに創出するか」という点について、「昨今、イノベーションが“技術革新”と誤解され、本来の意味である“価値創造”から離れつつある。イノベーションは価値ある発明のもとに成り立っており、その発明で社会を劇的に変革するビジネスモデルに落とし込み、社会に実装する、その過程を含めてイノベーションと言える。SDGsスタートアップは、共通言語であるSDGsという価値創造のタネをもとに事業を進めることができるため、ある点においてビジョンが見えやすいが、それが17のゴールとしていてはダメであり、17のゴールに紐づいている169のターゲットベースでの効果的なビジネスモデルを作成することが重要である」と強調。国内外で活躍しているSDGsスタートアップの具体的な取り組みや自身のこれまでの社会投資の経験から見える役立つ事例、特にSDGsに関係した「SDGs転換の実施」などについて紹介。講演後には参加者らと共に熱心にポジティブな意見交換が行われました。

岡山大学では引き続き教育・研究・社会貢献の面において、全学を挙げてSDGsを推進し、多様なステークホルダーとさらなる連携を深めていきます。さらにこれまで培ってきた岡山大学ならびに岡山の地での特色ある取り組みを継続しつつ、そこにいる多様なSDGs人材を用いて、国内外の産学官それぞれ分野への発信やプロジェクトの共創など、アカデミアの旗手として強力かつ、着実に推進していきます。

〇参考
・SDGs転換：アカデミアとSTI for SDGs　佐藤法仁URA・副理事がシンポジウム「SDGsを実現するためのイノベーション・エコシステム」に登壇（2018年7月11日）

・「社会貢献活動から本業へのSDGs転換～SDGsターゲットを明確にした事業構想～」について佐藤法仁URA・副理事が講演（2018年11月12日）

【本件問い合わせ先】
岡山大学リサーチ・アドミニストレーター（URA）室 [岡山大学東京オフィス]
TEL：03-6225-2905

SDGsスタートアップにおいて価値ある発明でイノベーションを創造できるビジネスモデルをいかに創出するかについて講演した佐藤法仁URA・副理事

岡山大学は、国連の「持続可能な開発目標（SDGs）」を支援しています。また、政府の第1回「ジャパンSDGsアワード」を受賞しています。

http://ura.okayama-u.ac.jp/topics/archives/20181112-%E3%80%8C%E7%A4%BE%E4%BC%9A%E8%B2%A2%E7%8C%AE%E6%B4%BB%E5%8B%95%E3%81%8B%E3%82%89%E6%9C%AC%E6%A5%AD%E3%81%B8%E3%81%AEsdgs%E8%BB%A2%E6%8F%9B-%E3%80%8D%E3%81%AB%E3%81%A4%E3%81%84%E3%81%A6%E4%BD%90%E8%97%A4ura%E3%83%BB%E5%89%AF%E7%90%86%E4%BA%8B%E3%81%8C%E8%AC%9B%E6%BC%94-2/

2019年3月28日木曜日

【情報発信】60年間支持されてきたタンパク質構造安定性理論の検証への挑戦

◆発表のポイント

タンパク質の構造安定性メカニズムを解析する新たな理論的計算手法を開発しました。
人工タンパク質Chignolinに本手法を適用したところ、60年間幅広く支持されてきたタンパク質構造安定性の理論「疎水性相互作用仮説」に関し、見直す必要性が示唆されました。
バイオ医薬品の開発や人工タンパク質の分子設計の指針となる、重要な知見であるといえます。

岡山大学異分野基礎科学研究所の墨智成准教授および甲賀研一郎教授は、タンパク質構造安定性のメカニズムを解析する新たな理論的計算手法を開発し、人工タンパク質Chignolinに適用しました。それにより、60年間幅広く信じられてきたタンパク質構造安定性の理論「疎水性相互作用仮説」とは異なる結論が、Chignolinに対して導かれました。折り畳みの駆動力は、周りに存在する水を介した「溶媒誘起力」というよりむしろ、「タンパク質内直接相互作用」に起因するという、極めてシンプルな結論です。

本研究成果は、３月２６日英国時間午前１０時（日本時間午後７時）、英国の科学雑誌「Scientific Reports」掲載されました。

疎水性相互作用仮説では、水と油が分離する現象になぞらえ、水が油を嫌うことに起因する「溶媒誘起力」に基づいて、タンパク質の天然構造安定性を説明しています。しかしながら、溶媒誘起力はむしろ、油（疎水性アミノ酸残基）を水中で分散する方向へ働いており、折り畳みの駆動力は、全てのアミノ酸残基間に存在するロンドン分散力1)を含む、タンパク質内直接相互作用であったのです。本研究成果は、これまで信じられてきた定説を見直す必要性を示唆しており、今後、バイオ医薬品の開発や人工タンパク質の分子設計の指針となる、重要な知見であるといえます。

◆研究者からのひとこと

約20年間に渡る液体・溶液の理論的研究の集大成となる、新たな方法論の開発となりました。今回は小さな人工タンパク質への適用でしたが、実験と一致する計算結果が得られた時には、研究を続けてこられて良かったと思いました。一方で、タンパク質科学において根強く支持されてきた疎水性相互作用仮説とは異なる結果でしたので、論文投稿から出版に辿り着くまでの約一年もの間、査読者による厳しい審査が続きました。今後はより大きなタンパク質へ本手法を適用し、「タンパク質内直接相互作用メカニズム」の一般性を幅広く認めてもらえるよう、頑張っていきたいです！

墨准教授

■論文情報
論文名： Theoretical analysis on thermodynamic stability of chignolin
掲載紙：Scientific Reports
著　者： Tomonari Sumi, Kenichiro Koga
D　O　I：https://doi.org/10.1038/s41598-019-41518-1

＜詳しい研究内容はこちら＞
60年間支持されてきたタンパク質構造安定性理論の検証への挑戦～タンパク質折り畳みの駆動力がタンパク質内直接相互作用に起因することを示唆～

＜お問い合わせ＞
岡山大学異分野基礎科学研究所
准教授　墨　智成
（電話番号） 086-251-7837

http://www.okayama-u.ac.jp/tp/release/release_id609.html

【情報発信】岡山県と｢大学と連携した地域産業振興｣に係る協力に関する協定を締結

岡山大学は3月25日、岡山県と「大学と連携した地域産業振興」に係る協力に関する協定を締結しました。

本協定は、岡山大学と岡山県が、県内企業の技術開発及び大学の教育・研究を促進するとともに地域活性化につなげることを目的とし、相互に協力していくために締結しました。

岡山県庁で行われた締結式には、槇野博史岡山大学長、伊原木隆太岡山県知事、立会人として中島博岡山県経済団体連絡協議会座長が出席。締結に先立ち、伊原木知事は「留学していたスタンフォード大学とシリコンバレーのようにお互いが高め合い、世界に冠たる存在になりたい。岡山県と岡山大学はその資質が十分にある」、槇野学長は「本学が推進するSDGs(持続可能な開発目標)では、大学の知を産業界の方々の課題解決に活用する取り組みを行っている。今回の協定により、その具体的な場を設けていただいた」、中島会長は「これを機に大学と産業界の敷居を低くし、交流を進めたい」とあいさつしました。三者が協定書に署名した後、今後の協力を誓い堅い握手を交わしました。

本協定に基づき、岡山県は、本事業に係る拠点を本学構内に設置。企業と大学とのマッチング支援や複数の企業及び研究者との連携構築に取り組むほか、企業人材を育てるための寄付講座の開設などを予定しています。

【本件問い合わせ先】
研究交流部研究交流企画課
TEL：086-251-8462

【情報発信】本学理学部生物学科学生２人が、第８回サイエンス・インカレで表彰

３月２、３日に立教大学池袋キャンパスで開催された、第８回サイエンス・インカレ（文部科学省主催）において、本学理学部生物学科の学生２人が表彰されました。
受賞した賞、研究のタイトルは以下のとおりです。

〇生物学科４年生　渡部遼馬さん
国立研究開発法人科学技術振興機構理事長賞（ポスター発表部門）
『免疫系がメダカの脳内で縄張り様個体出現を制御する？』

〇生物学科４年生　岡村彩子さん
サイエンス・インカレ奨励賞（ポスター発表部門）
『羽形成の新モデル～遅羽性遺伝子の作用機序の解明～』

２人とも、理学部フロンティアサイエンティスト特別コース（研究の最前線で活躍できる科学者や高度な専門技術者の育成をめざす、岡山大学理学部独自の特別コース）に所属。３年次より研究を続けており、今回の受賞はその成果が認められたものです。

サイエンス・インカレでは、これまでにも多くの本学理学部学生が各部門で成果を発表し、その内容が認められて表彰を受けています。岡山大学理学部はこれからもフロンティアサイエンティスト特別コースなどさまざまな形で学生の自主的な研究をサポートしていきます。

〇サイエンス・インカレ
学部学生の能力・研究意欲を高め、創造性豊かな科学技術人材を育成することを目的に、自然科学分野を学ぶ全国の学生が自主研究の成果を発表し競い合う場として平成23年度から開催されています。
（参考：サイエンス・インカレHP　http://science-i.mext.go.jp/about.php ）

【本件問い合わせ先】
岡山大学理学部事務室教務学生担当
（フロンティアサイエンティスト特別コース担当）
TEL：086-251-7778

2019年3月26日火曜日

【offer information】Okayama University announces its plan to offer the SiEED program designed to enhance students’ abilities to identify unknown problems and create unknown solutions

On December 6, Okayama University and Stripe International Inc. held a joint press conference in Tokyo to announce a plan to offer the SiEED program, which is designed to promote the creation of new businesses in Okayama by providing students with a new learning forum where they can be inspired to create a better future.

The speakers at the press conference were Okayama University’s President Hirofumi Makino; Dr. Yasutomo Nasu, Director of the Office for Innovative Medicine at the Organization for Research Promotion & Collaboration, who heads the SiEED Program Working Group; Mr. Yasuharu Ishikawa, President, CEO and Representative Director of Stripe International Inc.; Mr. Hitoshi Hokamura, Partner at Scrum Ventures and former Chairman of Evernote Japan, who serves as an executive advisor for this program; and Mr. Tetsuya Yamashita, Liaison Officer for 500 Kobe Accelerator, who serves as the program director. They all vigorously expressed their thoughts and aspirations about the SiEED Program, an innovative education program that will begin to be offered in April 2019.

Mr. Ishikawa said, “I’ve been conducting my business with the hope of spreading something good across society. Through the SiEED program, I’d like to help develop people.” President Makino said, “I’d like our faculty and students to change their mindsets through this program. We will continue to develop students into globally competent individuals.”

Okayama University will offer four liberal arts education courses under this program in the first and second semester of the academic year 2019.

2019年3月25日月曜日

【offer information】Professor Jian Feng Ma selected as one of the world’s most highly influential scientists for 4th straight year

Professor Jian Feng Ma from the Group of Plant Stress Physiology at Okayama University Institute of Plant Science and Resources (IPSR) has been named on the Global Highly Cited Researcher 2018 list, announced by Clarivate Analytics (the former IP & Science business of Thomson Reuters).
He was also listed as one of the “Highly Cited Researchers” in 2015, 2016 and 2017, making this the fourth straight year.

Prof. Ma has clarified many transport mechanisms for various minerals essential for plant growth and has been highly rated internationally as one of the world’s most influential scientific researchers in the field of plant & animal science.

Acclaimed worldwide each year, this list presents a selection of about 4,000 distinguished researchers (of whom about 90 belong to Japanese research institutes) whose published papers in 21 natural and social science research fields during the 11 years from January 2006 to December 2016 have been cited a very high number of times. Exceptionally large numbers of citations is considered one of the scientific community’s criteria for determining a paper’s significance and utility.

In August 2013, Okayama University was selected as one of 19 universities in Japan by the Ministry of Education, Culture, Sports, Science and Technology to participate in the Program for Promoting the Enhancement of Research Universities, which is designed to help Japanese universities and research institutes improve their research capabilities and increase their international research competitiveness. As a research university, Okayama University has excellent research capabilities. One of the University’s research institutes IPSR has the highest percentage of top 10 percent most highly cited papers published (the highest Q value) among natural science sub-organizations of Japanese universities, and Prof. Ma is a major driving force in enhancing the University’s research capabilities.

【offer information】Professor Hiroaki Suga of the University of Tokyo delivered a lecture

Okayama University invited Professor Hiroaki Suga of the School of Science at the University of Tokyo, who also serves as an executive adviser for Okayama University, to lecture for a President’s Seminar Series on November 14.
　
Prof. Suga delivered a lecture titled “Can university teaching staff make innovation happen?: A case study of the establishment of PeptiDream Inc.” His lecture attracted about 150 people—in addition to University department heads and faculty members, graduate students also attended the lecture because Prof. Suga is a graduate of Okayama University’s Faculty of Engineering. Based on his own experience, he shared his philosophy of research—“Once a nonconformist and unconventional idea is accepted, it will be taken as a pioneering idea.” He also talked about the details of his research and how he started his business. His lecture was followed by a lively Q&A session, where Prof. Suga answered participants’ questions about his research and attitude toward starting a business.
　
President’s Seminar Series is held to help raise awareness among Okayama University community members about various issues surrounding universities and to take action to deal with such issues by gaining insights from invited experts from all walks of life. The University’s president will continue hosting this series, thereby enabling many faculty staff members to deepen the knowledge they need to perform their duties through lectures given by invited experts from various circles.

【offer information】President Makino and two others visit the University of Michigan: Two universities agree to strengthen their mutual collaboration, with the 70th anniversary of opening of the University of Michigan’s Okayama Field Station (2020) approaching

On October 29, President Hirofumi Makino, Vice President for Global Engagement Strategy Atsufumi Yokoi, and Professor Masaharu Senoo, Dean of the Graduate School of Interdisciplinary Science and Engineering in Health Systems, visited the University of Michigan.

The year 2020 will mark the 70th anniversary of opening of the University of Michigan’s Okayama Field Station, which was the only American center of Japanese studies established in Japan back then. 　Five months prior to this visit, on June 1, Dr. Kiyoteru Tsutsui, Director of the University of Michigan Center for Japanese Studies, and his companion visited Okayama University to discuss possible future interaction and collaboration between the two universities with President Makino and other university officials. The purpose of this visit in October was to discuss a variety of issues to further promote interaction and collaboration between the two universities.

President Makino and two others visited various institutions of the University of Michigan, including the University of Michigan Health System (UMHS), which has a partnership agreement with Okayama University’s Medical School, the University of Michigan Medical Center and the University of Michigan Center for Japanese Studies, to discuss with officials at each institution how to promote interaction and collaboration for a better future for the two universities.

【offer information】“International Exchanges with Faculty, Staff and Students from Malaysia, P.R.China and Republic of Singapore”

From December 15-22, 10 young professors and post-graduate students visited Okayama University from Universiti Putra Malaysia, Zhejiang University, Zhejiang University of Technology and Xiamen University, with which Okayama University has concluded international exchange agreements, and from National University of Singapore, with which Okayama University is conducting joint research.

As well as engaging in discussions related to joint research, the participants conducted experiments on the synthesis of Biologically active organic compounds at the laboratory of Professor Sakakura.
This program was conducted by Technical Research Officer Ms. Yuri Nakamura of Faculty of Engineering and advised from Professor Masanobu Abe, Dean of the Faculty. Moreover, it coordinated across the whole university, they visited to Faculty of Engineering, Graduate School of Natural Science and Technology, Graduate School of Environmental and Life Science, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Center for Innovative Clinical Medicine, Public Relations and Information Strategy. Therefore, they can image several studies with the view of studying in Okayama University in near future.

As part of the program, they paid a visit to Professor Kanji Tsuru at Fukuoka Dental College and other researchers and took part in a seminar and discussion on new materials. They also visited Kabaya Foods Corporation and the Industrial Technology Center of Okayama Prefecture to learn about community-rooted yet global-oriented companies and research facilities.
This exchange project was organized young professors and students with different backgrounds such as nationality and academic fields. By inviting them all together, we were able to examine and ascertain things from various angles and approaches. Through this three-years project, we have deepened cooperation with overseas Universities.

Okayama University will continue to contribute to the development of human resources in the fields of science and technology.

This project was implemented as part of the Japan-Asia youth exchange program in science “Sakura Science Plan” of the Japan Science and Technology Agency.

【offer information】The Six National Universities Network (SUN)/ International Education & Research System (SixERS) in Japan signs the Awaji Island Declaration with Excellence League of China

On November 26, President Hirofumi Makino, a representative of the Six National Universities Network (SUN)/ International Education & Research System (SixERS) in Japan, and President Guo Dongming from Dalian University of Technology, who is in charge of Japanese affairs at Excellence League (Excellence 9) of China—an alliance of nine universities of excellence in China—signed the Awaji Island Declaration.
　
The signing ceremony was held in conjunction with the 5th Japan-China Conference on Education Exchange and Cooperation, which was also held on Awaji-shima Island. The ceremony was attended by about 320 people, including H.E. Mr. Cheng Yonghua, Chinese Ambassador to Japan; Mr. Li Tianran, Consul General of the Chinese Consulate General in Osaka; Mr. Kazuo Kanazawa, Vice Governor of Hyogo Prefecture; Mr. Tetsuhito Minami, Deputy Director of the Office for International Planning, Higher Education Bureau, Ministry of Education, Culture, Sports, Science and Technology; representatives from Excellence 9 and SUN/SixERS; and Japanese and Chinese educational experts and officials.
　
SUN/SixERS and Excellence 9 concluded an international exchange agreement in November 2016. To coincide with the 40th anniversary of the conclusion of the Treaty of Peace and Friendship between Japan and the People’s Republic of China, they signed this declaration with the hope of expanding mutual exchanges.
　
In the afternoon of the same day, the Japan-China University Presidents’ Forum, the Japan-China Medical Exchange Forum and the Japan-China Conference on Education Exchange and Cooperation were held. Japanese and Chinese participants discussed academic exchanges between the two countries from their own perspectives.

【offer information】Symposiasts of “10th International Symposium for Future Technology Creating Better Human Health and Society” visit Okayama University

Four researchers at Wayne State University in the United States, Korea Advanced Institute of Science and Technology in South Korea, and Technical University of Dortmund in Germany paid a courtesy visit to President Hirofumi Makino at Okayama University on January 15.　

The researchers came to Japan to attend the “10th International Symposium for Future Technology Creating Better Human Health and Society,” held by the Graduate School of Interdisciplinary Science and Engineering in Health Systems on January 16. During their visit, they exchanged views on Innovations with Social Issues, the theme of the symposium, with President Makino, Professor Masaharu Seno, the Dean of the Graduate School of Interdisciplinary Science and Engineering in Health Systems, and Ken Aoo, Senior Assistant Professor in the same department. President Makino explained our university’s commitment to the SDGs, while the researchers described efforts made at their universities and talked about the possibilities of exchanges. Through this visit, exchanges between the universities are expected to expand further in the future.

【offer information】Professor Jian Feng Ma Receives the AY2019 Japan Prize of Agricultural Science

The winners of the AY2019 Japan Prize of Agricultural Science were announced on February 12. This prize is awarded to researchers who have produced excellent results in the field of agriculture by the Association of Japanese Agricultural Scientific Societies (AJASS). Professor Jian Feng Ma of Okayama University Institute of Plant Science and Resources is one of the winners. The prize presentation ceremony will take place at the 90th Japan Agriculture Conference (in AY2019) held in the University of Tokyo Sanjo-Kaikan Hall on April 5, 2019.
　
The award of this prize, which is considered the highest honor among researchers of agriculture in Japan, is a tremendous validation of his achievements in the “study of mechanism of mineral transport in crop plants.” When he was named as a winner of the prize, Professor Ma said: “I’m very pleased that the AJASS has given me credit for my steady efforts. This award will encourage me to continue to make my utmost efforts.”

【offer information】Okayama University Medical Research Updates （OU-MRU） Vol.65　How do bacteria play Tag?

Source: Okayama University (JAPAN), Public Relations and Information Strategy

For immediate release: 18 March 2019
Okayama University research: Game changer: How do bacteria play Tag?

(Okayama, 18 March) In a recent study published in Proteins and Proteomics researchers at Okayama University show how bacteria attach to organisms before infecting them.

Bacteria have been long invading animals and plants. One of their most intricate but less understood mechanisms is their ability to adhere to other organisms. A research team led by Professor Takashi Tamura at Okayama University has unravelled the role of a molecule, DsbA, and how its chemical properties control this adhering function of bacteria.

Professor Tamura have previously shown that before bacteria can adhere to other living objects certain structures on the bacteria’s surface must be stabilized to form a strong scaffold. Special proteins found within the bacteria are responsible for this stabilization. To understand this process better, Professor Takashi Tamura’s team used a virus that attacks bacteria only (bacteriophage). This virus binds to an appendage-like structure found on the bacterial surface. DsbA is the protein responsible for stabilizing this appendage to facilitate this attachment. To decipher how DsbA does its job, the team created several mutants of bacteria, each with a different form of the DsbA protein. The code responsible for conferring DsbA a chemical charge was different in each mutant. A bacteriophage called as M13 was then introduced into these bacteria, grown on a plate.

Ideally, when M13 successfully attaches to and infects bacteria, “plaques” of viral colonies will be observed on the plate, in place of the bacterial colonies. These plaques were measured for all the different mutants. It was found that one particular mutant (DsbA [CDIC]) had 40 times more plaques than any other mutant or the unmutated bacteria. The charge on this mutant was much lower than the unmutated protein. However, another mutant, also with a low charge, did not have more plaques. This suggested that the mutated code of (DsbA [CDIC]) could be bringing about additional effects. Using structural mapping the team then found that DsbA [CDIC] had enlarged binding pockets, compared to the other variants. This could facilitate better binding of the scaffolding appendage.

Insights into these mechanisms of their attachment can help build strategies to combat bacteria. Antibiotic resistance is also spread from one bacterium to another by close contact. Designing drugs that could inactivate the factors driving DsbA function seems like one such strategy.

Background
Proteins and structure: Proteins that bind to and modulate the activity of other proteins are known as enzymes. Special regions on these proteins called active sites are responsible for this function. The active site consists of a ‘binding site’, a pocket where the partner protein actually binds and a ‘catalytic site’ which gives the protein a chemical charge. This charge provides the energy for the protein to undergo a chemical reaction. In the case of DsbA, codes on the catalytic site were changed to create the mutants.

Bacteriophage: Bacteriophage or “bacteria eaters” are viruses that attack and subsequently hijack bacteria. The first step in this process requires the bacteriophage to attach itself onto the bacterial surface. Typically, the bacteriophage does this by binding to F-pilus, an appendage-like structure found on the bacteria’s surface.

Reference
Shinya Sutoh, Yuko Uemura, Yuko Yamaguchi, Asako Kiyotou, Rena Sugihara, Makiko Nagayasu, Mihoko Kurokawa, Koreaki Ito, Naoki Tsunekawa, Michiko Nemoto, Kenji Inagaki, Takashi Tamura. Redox-tuning of oxidizing disulfide oxidoreductase generates a potent disulfide isomerase. Biochimica et Biophysica Acta - Proteins and Proteomics, 1867(2019), 194-201.
DOI : doi.org/10.1016/j.bbapap.2018.12.005

Correspondence to
Professor Takashi Tamura, Ph.D.
Department of Bioresources Chemistry,
Okayama University Graduate School of Environmental
and Life Science, 1-1-1, Tsushima-naka, Kita-ku, Okayama
700-8530, Japan.
E-mail: tktamura(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Okayama University Medical Research Updates （OU-MRU）
The whole volume : OU-MRU (1- )
Vol.1：Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2：Ensuring a cool recovery from cardiac arrest
Vol.3：Organ regeneration research leaps forward
Vol.4：Cardiac mechanosensitive integrator
Vol.5：Cell injections get to the heart of congenital defects
Vol.6：Fourth key molecule identified in bone development
Vol.7：Anticancer virus solution provides an alternative to surgery
Vol.8：Light-responsive dye stimulates sight in genetically blind patients
Vol.9：Diabetes drug helps towards immunity against cancer
Vol.10：Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11：Compound-protein combination shows promise for arthritis treatment
Vol.12：Molecular features of the circadian clock system in fruit flies
Vol.13：Peptide directs artificial tissue growth
Vol.14：Simplified boron compound may treat brain tumours
Vol.15：Metamaterial absorbers for infrared inspection technologies
Vol.16：Epigenetics research traces how crickets restore lost limbs
Vol.17：Cell research shows pathway for suppressing hepatitis B virus
Vol.18：Therapeutic protein targets liver disease
Vol.19：Study links signalling protein to osteoarthritis
Vol.20：Lack of enzyme promotes fatty liver disease in thin patients
Vol.21：Combined gene transduction and light therapy targets gastric cancer
Vol.22：Medical supportive device for hemodialysis catheter puncture
Vol.23：Development of low cost oral inactivated vaccines for dysentery
Vol.24：Sticky molecules to tackle obesity and diabetes
Vol.25：Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26：Protein for preventing heart failure
Vol.27：Keeping cells in shape to fight sepsis
Vol.28：Viral-based therapy for bone cancer
Vol.29：Photoreactive compound allows protein synthesis control with light
Vol.30：Cancer stem cells’ role in tumor growth revealed
Vol.31：Prevention of RNA virus replication
Vol.32：Enzyme target for slowing bladder cancer invasion
Vol.33：Attacking tumors from the inside
Vol.34：Novel mouse model for studying pancreatic cancer
Vol.35：Potential cause of Lafora disease revealed
Vol.36：Overloading of protein localization triggers cellular defects
Vol.37：Protein dosage compensation mechanism unravelled
Vol.38：Bioengineered tooth restoration in a large mammal
Vol.39：Successful test of retinal prosthesis implanted in rats
Vol.40：Antibodies prolong seizure latency in epileptic mice
Vol.41：Inorganic biomaterials for soft-tissue adhesion
Vol.42：Potential drug for treating chronic pain with few side effects
Vol.43：Potential origin of cancer-associated cells revealed
Vol.44：Protection from plant extracts
Vol.45：Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46：New method for suppressing lung cancer oncogene
Vol.47：Candidate genes for eye misalignment identified
Vol.48：Nanotechnology-based approach to cancer virotherapy
Vol.49：Cell membrane as material for bone formation
Vol.50：Iron removal as a potential cancer therapy
Vol.51：Potential of 3D nanoenvironments for experimental cancer
Vol.52：A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53：Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54：Measuring ion concentration in solutions for clinical and environmental research
Vol.55：Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56：New device for assisting accurate hemodialysis catheter placement
Vol.57：Possible link between excess chewing muscle activity and dental disease
Vol.58：Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59：Role of commensal flora in periodontal immune response investigated
Vol.60：Role of commensal microbiota in bone remodeling
Vol.61：Mechanical stress affects normal bone development
Vol.62：3D tissue model offers insights into treating pancreatic cancer
Vol.63：Promising biomarker for vascular disease relapse revealed
Vol.64：Inflammation in the brain enhances the side-effects of hypnotic medication

【offer information】Okayama University Medical Research Updates （OU-MRU） Vol.64　Inflammation in the brain enhances the side-effects of hypnotic medication

Source: Okayama University (JAPAN), Public Relations and Information Strategy

For immediate release: 06 March 2019

Okayama University research: Inflammation in the brain enhances the side-effects of hypnotic medication

(Okayama, 06 March) In a study recently published in the European Journal of Pharmacology researchers at Okayama University show how the presence of inflammation in the brain can increase its sensitivity to benzodiazepines.

Benzodiazepines (BZDs) are drugs commonly prescribed for anxiety, insomnia and seizures. However, in post-surgical patients taking BZDs, undue side-effects such as excessive sleepiness, weakness and delirium have often been observed. Associate Professor Yoshihisa Kitamura and and Professor Toshiaki Sendo from Okayama University and colleagues have recently shown that inflammation, which is a normal after-effect of surgery, might be potentiating the effects of these drugs.

BZDs act by activating a receptor in the brain known as the GABAA receptor (GABAR). Typically, GABAR is activated by chemicals inherently present in the brain. However, because drugs like BZDs can mimic these chemicals, they are used to stimulate the activity of GABAR in the lab. When GABAR is excessively activated, animals tend to exhibit inhibitory effects, such as loss of consciousness and loss of normal reflexes. One such reflex observed in animals is the righting reflex, that is, their tendency to immediately prop back up on their paws, when made to lay supine. This suggests that the animal is awake and alert.

For their study, the investigators first artificially stimulated GABAR in the brains of mice, using a sedative called pentobarbital. As expected, pentobarbital induced a loss of the righting reflex (LORR). Under normal conditions, BZDs should prolong the duration of the LORR, as they activate GABAR even further. This was observed with a high, but not low, dose of the BZD, diazepam. Another group of mice was then treated with a bacterial endotoxin that triggered inflammation in their brains. When this group was given diazepam, it prolonged the duration of LORR even at a low dose, suggesting a sensitivity to diazepam in the inflammation-induced mice.

To address if these effects were specific to GABAR, a drug that inactivates these receptors was subsequently used. The duration of LORR in these mice was considerably reduced, confirming the role of GABAR. Interestingly, even when the mice were given a drug that reduces inflammation, the duration of LORR was reduced. Inflammation was indeed the culprit. The prolongation of reflex loss seen in mice given diazepam was thus linked directly to GABAR and inflammation in the brain.

Associate Professor Yoshihisa Kitamura and and Professor Toshiaki Sendo from Okayama University and colleagues speculate that inflammation might result in an increase in the number of GABAR in the brain, which makes the inhibitory effects of diazepam more profound. “Thus, inhibition of inflammation in the brain may be a promising strategy to prevent the effects of benzodiazepines, such as weakness, over-sedation, and delirium, experienced in patients after surgery”, concludes his team. Prescribing anti-inflammatory drugs to these patients could, perhaps, be one such strategy.

Background
Inflammation:
Inflammation is a condition in which the body’s surveillance system secretes chemicals to the protect it from pathogens such as viruses and bacteria. The condition manifests as redness, swelling, and pain. In the case of neuroinflammation, microglia, the watchdogs of our brain are activated. Neuroinflammation is often associated with traumatic brain injury, neurodegenerative diseases and aging.

BZDs and GABA:
Gamma amino-butyric acid, or GABA, is a signalling chemical in the brain known as a neurotransmitter. GABA attaches to its receptor (GABAR) on the brain cells and induces inhibitory effects i.e., it decreases brain activity by calming it down. It has been stipulated that alcohol induces its effects by docking onto GABAR. Drugs that are similar in nature to GABA, and thereby activate its receptor, such as diazepam and pentobarbital are used in conditions such as anxiety, epilepsy and for anaesthesia. These are all conditions where brain activity needs to be subdued.

Reference
Yoshihisa Kitamura, Shiho Hongo, Yoshiaki Yamashita, Shinpei Yagi, Kanami Otsuki, Akihisa Miki, Ayumi Okada, Soichiro Ushio, Satoru Esumi, Toshiaki Sendo. Influence of lipopolysaccharide on diazepam-modified loss of righting reflex duration by pentobarbital treatment in mice. European Journal of Pharmacology, 2019 Jan 5;842:231-238.
DOI: 10.1016/j.ejphar.2018.10.049

Correspondence to
Associate Professor Yoshihisa Kitamura, Ph.D.
Department of Clinical Pharmacy,
Okayama University Graduate School of Medicine,
Dentistry, and Pharmaceutical Sciences, 2-5-1,
Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
E-mail: kitamu-y(a)cc.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
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For inquiries, please contact us by replacing (a) with the @ mark.
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Okayama University Image Movie (You Tube): https://www.youtube.com/watch?v=KU3hOIXS5kk

Okayama University Medical Research Updates （OU-MRU）
The whole volume : OU-MRU (1- )
Vol.1：Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2：Ensuring a cool recovery from cardiac arrest
Vol.3：Organ regeneration research leaps forward
Vol.4：Cardiac mechanosensitive integrator
Vol.5：Cell injections get to the heart of congenital defects
Vol.6：Fourth key molecule identified in bone development
Vol.7：Anticancer virus solution provides an alternative to surgery
Vol.8：Light-responsive dye stimulates sight in genetically blind patients
Vol.9：Diabetes drug helps towards immunity against cancer
Vol.10：Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11：Compound-protein combination shows promise for arthritis treatment
Vol.12：Molecular features of the circadian clock system in fruit flies
Vol.13：Peptide directs artificial tissue growth
Vol.14：Simplified boron compound may treat brain tumours
Vol.15：Metamaterial absorbers for infrared inspection technologies
Vol.16：Epigenetics research traces how crickets restore lost limbs
Vol.17：Cell research shows pathway for suppressing hepatitis B virus
Vol.18：Therapeutic protein targets liver disease
Vol.19：Study links signalling protein to osteoarthritis
Vol.20：Lack of enzyme promotes fatty liver disease in thin patients
Vol.21：Combined gene transduction and light therapy targets gastric cancer
Vol.22：Medical supportive device for hemodialysis catheter puncture
Vol.23：Development of low cost oral inactivated vaccines for dysentery
Vol.24：Sticky molecules to tackle obesity and diabetes
Vol.25：Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26：Protein for preventing heart failure
Vol.27：Keeping cells in shape to fight sepsis
Vol.28：Viral-based therapy for bone cancer
Vol.29：Photoreactive compound allows protein synthesis control with light
Vol.30：Cancer stem cells’ role in tumor growth revealed
Vol.31：Prevention of RNA virus replication
Vol.32：Enzyme target for slowing bladder cancer invasion
Vol.33：Attacking tumors from the inside
Vol.34：Novel mouse model for studying pancreatic cancer
Vol.35：Potential cause of Lafora disease revealed
Vol.36：Overloading of protein localization triggers cellular defects
Vol.37：Protein dosage compensation mechanism unravelled
Vol.38：Bioengineered tooth restoration in a large mammal
Vol.39：Successful test of retinal prosthesis implanted in rats
Vol.40：Antibodies prolong seizure latency in epileptic mice
Vol.41：Inorganic biomaterials for soft-tissue adhesion
Vol.42：Potential drug for treating chronic pain with few side effects
Vol.43：Potential origin of cancer-associated cells revealed
Vol.44：Protection from plant extracts
Vol.45：Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46：New method for suppressing lung cancer oncogene
Vol.47：Candidate genes for eye misalignment identified
Vol.48：Nanotechnology-based approach to cancer virotherapy
Vol.49：Cell membrane as material for bone formation
Vol.50：Iron removal as a potential cancer therapy
Vol.51：Potential of 3D nanoenvironments for experimental cancer
Vol.52：A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53：Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54：Measuring ion concentration in solutions for clinical and environmental research
Vol.55：Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56：New device for assisting accurate hemodialysis catheter placement
Vol.57：Possible link between excess chewing muscle activity and dental disease
Vol.58：Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59：Role of commensal flora in periodontal immune response investigated
Vol.60：Role of commensal microbiota in bone remodeling
Vol.61：Mechanical stress affects normal bone development
Vol.62：3D tissue model offers insights into treating pancreatic cancer
Vol.63：Promising biomarker for vascular disease relapse revealed

【情報発信】Okayama University Medical Research Updates（OU-MRU） Vol.65 発行「Game changer: How do bacteria play Tag ?」

岡山大学は3月18日、本学の強みである医療系分野の研究成果について、革新的な基礎研究や臨床現場、医療イノベーションなどに結びつく成果を英語で世界に情報発信するWebレター「Okayama University Medical Research Updates（OU-MRU）」のVol.65を発行しました。

2012年より岡山大学では、研究成果や知的財産活動などを英語で情報発信するWebマガジン「Okayama University e-Bulletin」を年3～4回発行。世界の大学・研究機関の研究者やマスコミ関係者などにニュースやトピックスを交えて配信し、岡山大学の海外への情報発信を強化と国際的知名度の向上などを推進しています。

OU-MRUは、e-Bulletinの姉妹誌として、岡山大学の強みある医療系分野とその融合分野などの更なる増強と本学研究者が同分野で発表したイノベーティブな研究成果を世界にタイムリーに発信するために発行しています。

本号では、岡山大学大学院環境生命科学研究科（農学系）の田村隆教授らの病原菌を殺さずに無毒化する対感染症の新戦略に繋がる可能性がある、病原細菌の感染と薬剤耐性の獲得に関わるS-S架橋形成メカニズム解明についての研究成果について紹介しています。

病原細菌はべん毛や繊毛、毒素注入器※1などの巨大タンパク質構造物を細胞表面に構築して、宿主への感染、薬剤からの忌避、さらに薬剤耐性の異種間伝播に用います。その構築にはタンパク質分子内のシステイン残基間に正しくジスルフィド（S-S）架橋を作る仕組みが必要で、酵素であるDsbAがその役割を担っています。

田村教授らは、DsbAの酸化力をチューニングするタンパク質工学の技術を開発して、酸化力の異なるDsbAを発現させた大腸菌によるFピリ（性繊毛）形成量を調査しました。その結果、DsbAが高い活性を発揮するための要件として、基質に結合する際に深い溝が形成されることを明らかにしました。

今回の研究成果は、病原性細菌が持DsbAの鍵穴に強く結合して、細菌のタンパク質複合体の構築を停止する新しい薬剤の開発を可能にします。この研究で開発された構造計算手法を活用すればアミノ酸配列から病原菌DsbAの立体構造と溝の形状計算が可能です。この戦略では淘汰圧が発生するリスクは極めて低く、病原菌と人類のいたちごっこに終止符を打つことができます。

岡山大学は、2013年8月に文部科学省がわが国のさらなる大学研究力向上や国際的な研究競争力強化等のために全国の大学・研究機関から選定した、「研究大学強化促進事業」の選定大学（国内19大学）です。世界で研究の量、質ともに存在感を示す「リサーチ・ユニバーシティ（研究大学）：岡山大学」の構築のため、強みある分野の国際的な情報発信を力強く推進していきます。また、強みある医療系と異分野融合から生み出される成果を社会や医療現場が求める革新的技術、健康維持増進へより早く届けられるように研究開発を推進していきます。

なおOU-MRUは、文部科学省「研究大学強化促進事業」の一環として実施されています。

※1：毒素注入器（毒素注入装置）
病原菌が、感染する宿主細胞にエフェクターと呼ばれる毒素タンパク質を打ち込む仕組みのことです。

Okayama University Medical Research Updates（OU-MRU）　Vol.65：Game changer: How do bacteria play Tag ?

＜Back Issues：Vol.57～Vol.64＞
Vol.57：Possible link between excess chewing muscle activity and dental disease　（大学院医歯薬学総合研究科（歯学系）皆木省吾教授、加藤聖也医員）
Vol.58：Insights Into Mechanisms Governing the Resistance to the Anti-Cancer Medication Cetuximab　（大学院医歯薬学総合研究科（歯学系）江口傑徳助教）
Vol.59：Role of commensal flora in periodontal immune response investigated　（大学院医歯薬学総合研究科（歯学系）森田学教授、福原大樹医員）
Vol.60：Role of commensal microbiota in bone remodeling　（大学院医歯薬学総合研究科（歯学系）森田学教授、内田瑶子歯科医師）
Vol.61：Mechanical stress affects normal bone development　（大学院医歯薬学総合研究科（歯学系）池亀美華准教授）
Vol.62：3D tissue model offers insights into treating pancreatic cancer　（大学院ヘルスシステム統合科学研究科狩野光伸教授＆大学院医歯薬学総合研究科（薬学系）田中啓祥助教）
Vol.63：Promising biomarker for vascular disease relapse revealed　（大学院医歯薬学総合研究科（医学系）渡辺晴樹助教、佐田憲映准教授）
Vol.64：Inflammation in the brain enhances the side-effects of hypnotic medication　（岡山大学病院薬剤部北村佳久准教授）

＜参考＞
・「Okayama University Medical Research Updates（OU-MRU）」バックナンバー
・岡山大学国際Webマガジン「Okayama University e-Bulletin」

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本号で紹介した研究成果を担当した田村隆教授

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