Nobel Lecture: Emmanuelle Charpentier, Nobel Prize in Chemistry 2020

Nobel Prize
8 Dec 202026:54

Summary

TLDRこのスクリプトは、2012年に発見された革命的な遺伝子編集技術、CRISPR-Cas9について語っています。この技術は、特定の遺伝子を認識し、修正することができるシンプルで多様性に富んだ方法です。スティープトコキュスピデス菌の研究を通じて発見され、病原菌と人体の相互作用を理解するのに役立ちました。ノーベル化学賞を受賞したこの技術は、科学コミュニティに広く採用され、遺伝子治療や作物改良など多岐にわたる応用が期待されています。

Takeaways

  • 🎓 スピーカーは1968年にフランスのシュベ・セザロスで生まれ、1995年にパリのインスティテュート・パスツールから博士号を取得しました。
  • 🔬 スウェーデンのウメオ大学で研究を行った後、現在はドイツベルリンのマックス・プランク病原体科学ユニットのディレクターを務めています。
  • 🏆 2020年のノーベル化学賞を共有し、ゲノム編集方法の開発に貢献したことで称賛されています。
  • 🧬 CRISPR-Cas9技術は、ゲノムの特定のDNAサイトを認識し、修正することができる革新的な方法です。
  • 🔍 CRISPR-Cas9は、カス9蛋白とRNAコンポーネントから構成され、RNAのガイドで特定のDNAサイトに結びつき、DNAを切断することができます。
  • 📈 この技術は科学界で広く採用されており、2012年に発見されてから急速に人気を得ています。
  • 🧬 ゲノム編集は、細菌やウイルスからの研究を通じて開発された多くの技術の中で、CRISPR-Cas9はそのうち最もプログラム可能で簡単で多用途であると評価されています。
  • 🔬 スピーカーの研究は、細菌の病原性とそれに関連する遺伝子表現を理解することに焦点を当てられており、CRISPR-Cas9技術はこの研究を促進する重要なツールとなっています。
  • 🌐 CRISPR-Cas9は、遺伝子の修正、新しい遺伝子の導入、特定の遺伝子の削除や置換など、多様なゲノム編集を可能にします。
  • 🌱 この技術は、医学、植物生物学、基礎研究など、幅広い分野で応用されており、生命科学の研究と治療に変革をもたらしています。
  • 🔬 CRISPR-Cas9は、細菌とウイルスから派生した研究に基づくもので、その他にも細菌やウイルスからの研究が新しい生物科技の開発に寄与すると示唆しています。

Q & A

  • エマニュエル・シャルポンジュはどこで生まれましたか?

    -エマニュエル・シャルポンジュは1968年にフランスのシュベー・セザロスで生まれました。

  • シャルポンジュ博士はどこでPhDを取得しましたか?

    -シャルポンジュ博士は1995年にパリのインスティテュト・パスツールでPhDを取得しました。

  • チャープリー・カス9技術とは何ですか?

    -チャープリー・カス9技術はゲノム編集のための新しい方法で、特定のDNAのサイトを認識し、遺伝子を修正する能力を持つ技術です。

  • チャープリー・カス9技術の特長は何ですか?

    -チャープリー・カス9技術は複雑でシンプルで、非常に効率的で多様な用途に使われることができます。

  • チャープリー・カス9技術はどのように機能しますか?

    -チャープリー・カス9技術はカス9タンパク質とRNAコンポーネントから成り立ち、RNAが特定のDNAサイトにカス9を誘導してDNAを切断します。

  • チャープリー・カス9技術が開発された背景は何ですか?

    -チャープリー・カス9技術は、細菌とウイルスの研究を通じて開発され、遺伝子の機能を理解するために必要な正確な遺伝学技術を提供する目的で開発されました。

  • チャープリー・カス9技術はどのように科学界に影響を与えていますか?

    -チャープリー・カス9技術は科学界に広く採用され、細胞や生物の研究において難しくあった遺伝子編集が可能になりました。

  • チャープリー・カス9技術はどのような種類の研究に使われていますか?

    -チャープリー・カス9技術は基礎研究や臨床研究、植物生物学、遺伝子療法など、多岐にわたる研究分野で使われています。

  • チャープリー・カス9技術の進化はどのように進んでいますか?

    -チャープリー・カス9技術は継続的に進化しており、新しいチャープリー・カスシステムが発見され、遺伝子編集のツールボックスが拡大しています。

  • チャープリー・カス9技術の未来的な展望は何ですか?

    -チャープリー・カス9技術は、基礎研究や臨床研究、植物生物学などにおいて、さらに多くの応用が期待されており、将来的にはさらに多くの遺伝子技術が開発されるでしょう。

Outlines

00:00

🏆 CRISPR-Cas9技術の受賞とその意義

この段落では、講演者は1995年にパリのインスティテュート・パステュールから博士号を取得し、後にスウェーデンのウメオ大学で研究を行ったエマニュエル・カルパンテ博士が、2020年のノーベル化学賞を受賞したことを紹介しています。受賞理由は、ゲノム編集のための新しい方法であるCRISPR-Cas9技術の開発です。この技術は、特定の遺伝子を特定し、DNAを正確に編集できるシンプルで多様性に富んだものであると説明されています。

05:02

🔬 細菌とホストの相互作用とCRISPR-Cas9の発見

第2段落では、細菌がどのように環境と相互作用し、特に人体内で疾病を引き起こし、適応し、生存するかを研究した経緯が語られています。また、細菌とホストの相互作用に関する研究を通じて、CRISPR-Cas9技術の前身となった小RNAの研究が進展した経緯が紹介されています。この研究は、細菌の変異因子の表現を制御する小RNAを発見し、後にCRISPR関連蛋白を含む遺伝子と関連する小RNAであるtracer RNAを特定しました。

10:03

🛡️ CRISPR-Cas9の免疫系由来と機能

第3段落では、CRISPR-Cas9技術が細菌と古菌が進化させて病毒などの遺伝子要素の侵入に対抗する免疫系として由来するものであることが強調されています。CRISPR-Cas9は、細菌が感染を認識し、記憶し、2回目の感染時に特定のDNAを認識して切断する機能を持つアダプティブな免疫系です。この段落では、CRISPR-Cas9の仕組みと、その科学的な背景について詳しく説明しています。

15:04

🧬 CRISPR-Cas9の科学的な進化と応用

第4段落では、CRISPR-Cas9技術がどのように科学界で進化し、多様な応用へと発展したかが語られています。この技術は、遺伝子の修正、新しい変異の導入、遺伝子の削除や入れ替えなど、多岐にわたるゲノム編集が可能であると紹介されています。また、この技術がどのように科学者たちによって迅速に採用され、多様な細胞や生物で効率的に機能するかについても触れられています。

20:06

🌐 CRISPR-Cas9技術の未来展望と科学コミュニティへのメッセージ

第5段落では、CRISPR-Cas9技術の未来の展望と、細菌やウイルスに関する研究の重要性が強調されています。この技術は、基礎研究から医療、植物生物学、遺伝子医薬品開発などへの応用が期待されています。また、研究者は新しいCRISPR関連システムを発見し、この分野をさらに発展させていくことができました。講演者は、若い科学者たちにこの分野の研究を続けることを励ましています。

25:07

🙌 CRISPR-Cas9研究への感謝の言葉

最後の段落では、CRISPR-Cas9技術の研究に貢献した人々への感謝の言葉が述べられています。講演者は、研究を進める上での協力者、学生、そして自分の家族や友人に感謝しています。また、この技術がどのように科学コミュニティによって迅速に採用され、発展してきたかについても触れられています。

Mindmap

Keywords

💡CRISPR-Cas9

CRISPR-Cas9は、ゲノム編集のための革新的な技術であり、このビデオの中心となるテーマです。CRISPRは、細菌と古菌が進化させて病毒などの外來的な遺伝子要素に対する免疫系を形成したものであり、Cas9はその一種の核酸酸酵素で、特定のDNAの部位を認識し切断することができます。ビデオでは、この技術がどのように開発され、ゲノム編集にどのように役立つかが説明されています。

💡ゲノム編集

ゲノム編集は、生物のDNAの特定の部分を変更するプロセスで、CRISPR-Cas9技術によって可能になりました。ビデオでは、ゲノム編集が遺伝子を修正したり、新しい遺伝子を導入したり、特定の遺伝子を削除することができると説明されています。これは、医学研究や治療、そして農業生物技術の分野で重要な突破をもたらしました。

💡ノーベル賞

ビデオでは、講演者が2020年の化学ノーベル賞を受賞し、CRISPR-Cas9技術の開発に貢献したと述べています。ノーベル賞は、物理学、化学、生理学・医学、文学、平和の6つの分野で、その分野において最も優れた業績を残した個人や集団に贈られる国際的な賞です。

💡細菌

細菌は、このビデオの重要な要素で、CRISPR-Cas9技術の起源を説明する上で欠かせません。細菌は、CRISPR-Cas9システムを通じて、自己の遺伝子組に対する病毒の侵害から防御する能力を発展させました。ビデオでは、細菌がどのようにこのシステムを利用して遺伝子情報を保存し、病原体に対する免疫を獲得するかが議論されています。

💡遺伝子変異

遺伝子変異は、遺伝子のDNAの変化であり、CRISPR-Cas9技術によって意図的に誘導することができるとビデオで説明されています。この技術は、遺伝子変異を通じて特定の遺伝病や癌の治療に役立つ可能性があります。

💡RNA

RNAは、CRISPR-Cas9システムの重要な部分であり、ビデオでは、RNAがどのようにCas9蛋白と結びつき、特定のDNAの部位を見つける手引きとして機能するかが説明されています。RNAは、遺伝子の表現を調節するだけでなく、CRISPR-Cas9技術でDNAの特定部位を認識する鍵となる役割を果たします。

💡免疫系

免疫系は、生物が病原体や外來的な要素に対する防御機構を形成するメカニズムであり、ビデオでは、CRISPR-Cas9が細菌や古菌の免疫系の一部であることが強調されています。このシステムは、細菌が過去の病原体に対する免疫を獲得し、再感染に対して迅速に対応するのに役立ちます。

💡プログラム性

CRISPR-Cas9技術のプログラム性は、特定のRNA分子を設計して、Cas9蛋白を特定のDNAの部位に誘導することができるという点にあります。ビデオでは、このプログラム性がどのように技術の柔軟性と多様性を高め、特定の遺伝子ターゲットを効率的に編集可能にするかが説明されています。

💡遺伝子治療

遺伝子治療は、遺伝子レベルでの治療法であり、CRISPR-Cas9技術を通じて特定の遺伝子を修正することで、遺伝性疾病や癌などの治療が可能になるという期待があります。ビデオでは、この技術が将来の医学的応用において、どのように重要な役割を果たす可能性があるかが議論されています。

💡多能性

CRISPR-Cas9技術の多能性は、さまざまなタイプの細胞や生物において、遺伝子を編集できる柔軟性があることを指します。ビデオでは、この技術が哺乳類、昆虫、魚、植物など多様な生物において応用されており、医学研究や農業生物技術の分野で革新的な進展をもたらしていると説明されています。

Highlights

1968年出生于法国Chevy Cesaros,1995年在巴黎巴斯德研究所获得博士学位。

曾在瑞典于默奥大学工作,现为德国柏林马克斯普朗克病原体科学单位的主任。

与Jennifer Darner共同获得2020年诺贝尔化学奖,以表彰CRISPR-Cas9基因编辑技术的发展。

CRISPR-Cas9技术是一种新颖的基因组编辑方法,具有高度的精确性和简单性。

CRISPR-Cas9技术由Cas9蛋白和RNA组成,Cas9蛋白具有特异性识别和切割DNA的能力。

CRISPR-Cas9技术自2012年发现以来,已被科学界广泛采用。

CRISPR技术是细菌和古菌为抵御病毒等遗传元素入侵而演化出的适应性免疫系统。

CRISPR-Cas9系统通过RNA引导Cas9蛋白至目标DNA序列进行特异性切割。

CRISPR-Cas9技术的可编程性使其在基因组编辑方面具有独特的优势。

CRISPR-Cas9技术的发展为研究难以研究的细胞和生物体提供了可能。

CRISPR-Cas9技术在医学、植物生物学和其他领域具有广泛的应用前景。

CRISPR-Cas9技术可以用于纠正突变、引入新突变、删除或替换基因等。

CRISPR-Cas9技术的发展得益于多个科学家的先驱工作和持续研究。

CRISPR-Cas9技术为年轻科学家提供了强大的工具,以研究他们感兴趣的细胞和生物体。

CRISPR-Cas9技术与其他基因技术相结合,为疾病治疗提供了新的可能性。

CRISPR-Cas9技术的发展强调了微生物研究在新型生物技术发展中的重要性。

CRISPR-Cas9技术的发现和应用是跨学科合作和创新的典范。

CRISPR-Cas9技术为基因编辑提供了前所未有的精确性和灵活性。

Transcripts

play00:03

was born

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in 1968 in chevy cesaros

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in france she obtained her phd

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in 1995 from institute pasteur

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in paris and for part of her career she

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worked

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at umeo university in sweden

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she is now director of the max planck

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unit

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for the science of pathogens in berlin

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germany

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i now welcome you onto the stage we are

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very much looking forward to hearing

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your lecture

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dear ladies and gentlemen i am delighted

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to welcome you to my

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nobel lecture it is the greatest

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honor to be awarded together with

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jennifer darner the nobel prize in

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chemistry for the year 2020 for the

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development of a method for genome

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editing i would like to warmly

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thank the members of the royal swedish

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academy

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of sciences the members of the nobel

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committee and all scientists

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who have supported our nomination

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i wish we'll be able to give the lecture

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live

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unfortunately it is a recorded lecture

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but i hope you will

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enjoy the recording

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i would like to start with explaining

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you the crispr cas9 technology that

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is this novel method for genome editing

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so over the years all biologists have

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been

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extremely interested in always using

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genetics to understand the functions of

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genes and

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we're always in need of precise genetics

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that allows to recognize sites

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specifically

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dna of genomes of cells and organisms

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and allows to modify genes and their

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expression and this is what the crispr

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cas9 technology does

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the particularity of this technology is

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that it's a

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sophisticated technology yet very simple

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versatile it works very efficiently and

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it is composed of

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an protein component called cas9 that is

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represented on this slide as scissors

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this protein casino

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has the ability to recognize such

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specifically a certain sequence

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on the dna certain sequence of interest

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has the ability to cleave

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the dna and this cas9 protein is

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programmed by the help of an

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rna component that allows to bring

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kas9 to the site of interest so this is

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a technology that has

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largely been adopted by the scientific

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community

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and has become very popular since the

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start of its

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discovery in 2012. so i would like to

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actually explain you also

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why this technology is transformative

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so the field of genetics started in the

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19th century up to the

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mid-20th century whereby rules for

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fundamental genetics

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were established with the dna that was

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isolated the dna that was shown to be

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the carrier of information

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and then the genetic code that was

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deciphered

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over the last years in the 60s

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the last 50 years have witnessed the

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large development of

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of a number of technologies actually

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all originating from research done on

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bacteria

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and and viruses and this started in the

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70s

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with different types of enzymes and

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technologies that would allow to

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recombine dna to clone dna to sequence

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dna amplified dna

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target genes and their expression

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the zinc finger and tannin nucleuses

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that were discovered

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over the last 20 years allowing precise

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genetics the same that what chris

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barcas9 does

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except that chris parkas9 brings a level

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of programmability and a level of

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of simplicity and versatility that is

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quite unique

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so we are all very happy because we can

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now

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study cells and organisms that were

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difficult to study prior to chris

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barcas9

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the research on chris pakistan

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originates in

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in my love from our interest in

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understanding

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how streptococcus powderiness causes

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diseases in humans so streptococcus

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biogenes belongs to the class of

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gram-positive

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bacteria such as listeria and

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staphylococci

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this bacteria have been the main focus

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of my

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research during my career

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i have always been interested in

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understanding

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how bacteria interact with their

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environment so in principle the human

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host

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how they can cause diseases how they can

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adapt to their environment

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survive in the human host and also to a

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certain extent how the human host can

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defend itself against bacterial

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infections

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so the focus was always on regulatory

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mechanisms

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that use proteins and small rnas

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the family of small rnas it's an

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interesting

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family of regulatory elements

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which we started to work on at the

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beginning of

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2000 so about 20 years ago

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and this research always was

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mixed with always a

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need to develop gene technologies along

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the way

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just to be able to study better those

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mechanisms in bacteria

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specifically in the context of their

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interactions with the human host

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and during my my years as a phds and

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postdocs i was

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certainly and decapped by the

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the the non-possibility to perform

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genetics in human cells which

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is really the are the hosts for this

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strict human pathogens so i have

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developed genetic tools in bacteria i

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have also worked on transgenic mice

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coming back to understanding the

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interaction between bacteria and the

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human host and understanding as well

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that there was a

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lack of tools that would allow to

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perform precise genetics in

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in human cells for example in this this

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is what chris park castleman can

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can do the

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the field of of small rnas has largely

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evolved the last 30 years and this was a

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discovery that

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rna molecules in addition to b messenger

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rna

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or transfer rna or ribosomal rnas and

play06:54

being involved in

play06:55

in the transcription of the dna into a

play06:58

translation into

play07:00

proteins that rnas had also regulatory

play07:03

functions and would be able to interact

play07:06

with messenger rna molecules and also

play07:08

with proteins

play07:09

and regulate the expression of genes

play07:12

what was not identified at the let's say

play07:16

about 10-15 years ago

play07:18

these were small rnas that would have

play07:20

the ability to

play07:21

to change gene expression by interacting

play07:24

directly

play07:25

with dna we were working on some small

play07:29

regulatory rnas

play07:30

we published some data showing that

play07:34

some of these small regulatory rnas had

play07:37

the ability to

play07:38

change the expression of virulence

play07:40

factors in bacteria so contributed a lot

play07:43

to the adaptation of bacteria to their

play07:45

environment

play07:46

and we decided in about 15 years ago

play07:50

to start a search for additional

play07:53

regulatory

play07:54

rnas we found a number of those rnas and

play07:57

we particularly picked an rna and that

play07:59

is

play08:00

known as tracer rna because this rna was

play08:03

very well

play08:04

expressed in in bacterial cells and you

play08:07

can see the gel that is a northern blood

play08:08

analysis showing the

play08:10

the expression of these rnas as

play08:12

different forms

play08:13

in in streptococcus biogenes

play08:17

we had found a target for this small

play08:19

regulatory rna so initially we thought

play08:22

that it would have a role in

play08:24

regulating the expression of the

play08:25

variance factor and we had difficulties

play08:27

to make sense of this

play08:29

interaction but what was clear is that

play08:31

at least this

play08:32

rna was encoded in the vicinity of a

play08:35

gene that was annotated to be a gene

play08:38

including a protein that is uh

play08:41

was crispr related protein containing

play08:44

two nucleus domains so

play08:46

a crispr protein that would have the

play08:48

ability to cleave

play08:50

nucleic acids so this was the start of

play08:53

none nevertheless continuing our

play08:55

research on tracer rna

play08:56

but also working on crispr

play09:00

so crispr is to be

play09:03

seen and and considered as part of

play09:06

of different systems which bacteria and

play09:09

archaea

play09:10

have evolved over millions of years

play09:14

so back then archaea can be infected by

play09:16

viruses as we can be

play09:18

infected by viruses and bacteria and

play09:20

have evolved

play09:22

diverse immune systems that allow them

play09:24

to cope with

play09:26

the invasion of genetic elements

play09:29

such as viral elements but also other

play09:32

elements such as plasmins and

play09:33

transposons

play09:35

and this really actually is important

play09:39

and to be seen in the context of of the

play09:42

fitness of the bacteria with their

play09:43

environment and the evolution

play09:45

of of the microorganisms so here on this

play09:48

slide you can see

play09:49

a phage that is infecting a bacterial

play09:52

cell

play09:53

with the genomic component of

play09:56

of the phage that is injected into the

play09:58

bacterial cell

play10:00

the genomes of of the virus that can

play10:02

replicate

play10:03

and then you have the formation of our

play10:05

particles

play10:06

that can uh lies back to our cells and

play10:09

propagate

play10:10

to lies further back to ourselves so

play10:12

here we deal with phages viruses that

play10:14

can kill bacterial cells and surely

play10:17

the the the need for bacteria to have

play10:20

evolved system that

play10:21

allow to uh to defend themselves

play10:24

against deaths so what is interesting is

play10:27

that some of these

play10:29

immune systems have been developed over

play10:32

the years

play10:33

as genetic tools so for example

play10:35

restriction enzymes are

play10:37

originally actually

play10:40

different systems existing in in

play10:42

bacteria

play10:44

crispr is is unique in the sense that

play10:47

it is an adaptive immune system there is

play10:49

a first step of

play10:51

of recognition that leads to the to the

play10:55

immunity and it is composed of

play10:58

protein components the cast proteins and

play11:01

rna components the crispr

play11:03

rna so i do not have the time to

play11:06

go very deeply into the history of

play11:10

of the chris parkas research however i

play11:13

would like to mention

play11:14

that uh this has involved a number of

play11:18

scientists who have really performed

play11:20

a pioneer work on chris barcas i have

play11:23

read

play11:24

all the the publications on chris parkas

play11:27

when we started to work on

play11:28

on the crisper cast 9 system in my lab

play11:31

and this has

play11:32

this is really by reading all those

play11:34

articles that

play11:36

that it allowed me to to really

play11:39

understand what would be different of

play11:40

the chris

play11:41

cas9 system compared to other krispaka

play11:44

systems that were

play11:45

studied by my colleagues but in brief

play11:49

the the crispr components are

play11:52

such that the first identification where

play11:56

the repeats of the crispr array so

play11:58

the crispr array is formed by very short

play12:02

sequences

play12:03

that are identical to one another that

play12:05

forms

play12:06

repeats and that are interspaced by

play12:09

sequences

play12:10

that have as origin mobile genetic

play12:13

elements this crispr array was shown to

play12:17

be able to

play12:18

be transcribed into rna molecules of

play12:21

different sizes so probably

play12:23

maturation events taking place to

play12:25

activate

play12:26

those crispr rna molecules in the

play12:28

vicinity of the crispr array

play12:30

you have the crispr associated genes

play12:33

that encode the crispr associated

play12:34

proteins and and very fast as well there

play12:36

was

play12:37

the observation that these crispr

play12:39

associated proteins

play12:41

contain domains that are homologous

play12:44

to domains contained in proteins that

play12:47

have the ability to

play12:48

target dna target rna and also cleave

play12:51

dna

play12:52

and cleave rna so all together the idea

play12:54

was that

play12:55

these crispr systems would be obviously

play12:59

adaptive immune systems in bacteria and

play13:00

archaea

play13:01

that was shown experimentally later on

play13:04

in streptococcustomophilus

play13:06

but that also those those

play13:09

systems were identified as prokaryotic

play13:13

rna interference systems by analogy to

play13:16

rna interference systems

play13:19

so when we started uh the research

play13:22

the dogma was that there would be a

play13:26

crisp complex of crispr associated

play13:29

proteins that will be formed

play13:30

and that will associate to the crispr

play13:32

rna

play13:34

to act as a machinery that would allow

play13:37

to target the dna or the rna

play13:40

so the way it works is as follows

play13:44

the system is adaptive in the sense that

play13:46

the bacteria are

play13:47

first to recognize the virus and

play13:50

will have the ability to memorize the

play13:53

infection

play13:54

by the virus and this is the way it is

play13:56

done

play13:57

so the virus will inject its its dna

play14:00

into the bacterial cell

play14:01

the chris parker system will be able to

play14:03

recognize

play14:04

the invading dna cleave

play14:08

a certain sequence of of the invading

play14:11

dna and insert

play14:12

this sequence into the crispr array and

play14:14

this is working as a kind of

play14:16

memorization

play14:17

of the virus and then you will have

play14:20

expression

play14:22

at the rna level of these memorized

play14:25

elements of viral infections

play14:28

the crispr rnas will associate with a

play14:31

complex of crispr associated

play14:33

proteins and those rnas allowing to

play14:37

guide the crispr associated proteins

play14:39

to the the invading dna of the virus

play14:43

upon a second infection

play14:45

and this is the way it works and there

play14:47

will be recognition of the virus and one

play14:49

protein of the chris barkas system will

play14:52

ultimately cleave the invading dna

play14:56

and the dna cannot replicate and this is

play14:58

a dead end for for the virus

play15:00

so this is globally uh how it works

play15:04

um in streptococcus pargenes we were

play15:06

lucky enough

play15:07

to uh have on on on the genome of

play15:10

streptococcus pyrogenes

play15:12

genes that were belonging to a certain

play15:15

type of chris parker system that was not

play15:17

studied yet at least at the molecular

play15:20

level

play15:21

what the the groups of of of

play15:27

the crisper casing system was really uh

play15:30

in streptococcus

play15:31

thermophilus uh implying uh

play15:34

involving one crispr associated protein

play15:38

cas9 that will be involved in

play15:40

in the recognition of the virus upon

play15:42

second infection but the molecular

play15:44

mechanism

play15:45

was not described and this is what we

play15:47

started in in our lab so

play15:50

we and decided to look at

play15:53

the the question whether tracer rna

play15:56

would actually have a regulatory role on

play15:58

the chris parker system

play16:00

and this is what we found what we found

play16:02

is that tracer rna

play16:03

contains an anti-repeat sequence that

play16:06

allows it

play16:07

to base pair with the repeats

play16:10

of the crispr rnas and this duplex of

play16:13

rna

play16:14

is actually stabilized by the protein

play16:17

cas9

play16:20

then following this this

play16:25

is going to be maturated by enzymes and

play16:28

in the bacter specifically the the rnas

play16:32

three and further are rnases that will

play16:35

lead to the mature form

play16:37

of the duplex of rna still bound to the

play16:39

protein casino

play16:41

then this complex of cas9

play16:45

guided by the duplex of rna will be able

play16:48

to recognize

play16:49

specifically the dna and cleave the dna

play16:52

using two nuclease domains and cleave

play16:54

the dna in

play16:55

a sequence specific manner so this is

play16:58

what we have shown

play16:59

uh seeing right away that the system

play17:02

from streptococcus biogenes was

play17:04

working very efficiently with cleavages

play17:07

that were

play17:08

as those we were expecting

play17:12

and now with regard to the

play17:14

programmability of

play17:16

of the system the idea was to simplify

play17:19

this duplex of rna and fuse those two

play17:23

rnas to have a single guard rna

play17:25

that would be the programmable element

play17:27

of the crispr casting system so bringing

play17:29

simplicity

play17:30

for the design of the technology one

play17:33

thing that is important to mention is

play17:35

that

play17:36

the the mechanism is very sophisticated

play17:39

in the sense that

play17:40

the ability to use two nucleus domains

play17:43

to cleave the dna

play17:44

and this programmability allowed to

play17:47

develop

play17:48

the cas9 technology further into a

play17:50

technology

play17:51

that can really perform multiple

play17:53

modifications

play17:55

on on the genome so it can

play17:58

correct mutations introduce

play18:01

new mutations on the dna it can allow to

play18:03

delete genes delete certain sequences of

play18:06

dna

play18:07

add new sequences of dna at the site of

play18:10

interest

play18:11

replace genes by other genes and over

play18:13

the last

play18:14

eight years a number of scientists and

play18:16

developers

play18:18

have really put forward the technology

play18:22

to really have the technology

play18:26

evolving in multiple versions that allow

play18:30

to do some multiplexing

play18:32

and that really allow to perform precise

play18:36

genetics in an unprecedented

play18:38

manner very fast actually scientists

play18:42

adopted this this technology and showed

play18:46

in a very very short amount of time that

play18:49

the technology was efficient

play18:52

to act on on the dna and modify genes

play18:55

and their expression

play18:56

in a variety of cells including human

play18:59

cells

play18:59

in organoids in modal organisms such as

play19:02

mice fish

play19:05

fly and also plants so a very

play19:08

transformative

play19:10

technology i do not have for sure the

play19:14

time to explain you all the details of

play19:16

the science beyond

play19:17

behind the crispr castline system but

play19:20

chris parkas is a largely evolving

play19:23

system

play19:24

all the chris barker systems including

play19:26

crisper cas9

play19:27

and this is early on the diversity

play19:32

of this system that we understood

play19:35

what would be conserved and what will be

play19:37

the basis of the mechanism so release

play19:39

this cas9 protein

play19:41

guided by a duplex of rna and that could

play19:44

be

play19:44

among all the different crispr systems

play19:47

existing

play19:48

that will be the system minimal enough

play19:50

to

play19:51

harness as a powerful gene technology

play19:54

and this is quite amazing how the

play19:57

the systems have evolved they have

play19:59

evolved surely in multiple

play20:01

other systems than the crispr castline

play20:03

system now we have

play20:05

two classes identified and within

play20:08

each of the class multiple systems and

play20:11

subsystems so since chris parkas9

play20:14

other minimal systems have been

play20:17

identified

play20:18

further developed also as chris parkas

play20:21

technologies so enlarging the chris

play20:23

podcast toolbox

play20:25

you have large applications for this

play20:28

genome editing

play20:29

technology so for sure for to understand

play20:33

better mechanisms of of life so it's

play20:36

very useful for fundamental research

play20:39

to unravel novel molecules novel

play20:42

pathways

play20:43

to be able to really work with the

play20:46

the cells and organisms that are of

play20:48

interest

play20:49

for clinical purposes the technology has

play20:52

been also

play20:53

uh very well developed with regard to

play20:58

the applications in understanding better

play21:01

the mechanisms of of life sciences in

play21:04

modern organisms

play21:05

such as mice drosophila and and fish

play21:09

it has also been a game changer for

play21:12

allowing precise genetics in plants

play21:14

and it has large applications in

play21:17

medicine either directly

play21:19

or indirectly by

play21:22

allowing to develop better models of

play21:25

diseases

play21:26

and also by allowing to develop the

play21:29

crispr cas9 technology as a direct

play21:32

tool for really

play21:35

to work as a gene medicine and

play21:39

use the technology directly to treat

play21:41

certain types of

play21:42

of diseases such as human genetic

play21:45

disorders

play21:46

or certain cancers by combining

play21:51

the crispr cas9 technology with

play21:54

immunotherapy it's also

play21:58

very transformative in the field of

play21:59

plant biology

play22:01

with the production of plant crops

play22:03

surely with ethical considerations

play22:05

that have to be taken into account

play22:10

what next so surely the crispr

play22:13

biologists continued to to work on this

play22:15

field

play22:16

continue to identify novel chris parker

play22:19

systems

play22:21

thanks to the sequencing of novel

play22:23

genomes of

play22:24

of bacterial species and rkr species

play22:28

recently novel defense systems in

play22:31

bacteria and

play22:32

archaea have been identified and and

play22:35

this will continue so

play22:36

we can expect from research on on

play22:39

microbes

play22:40

to have further genetic technologies to

play22:43

be

play22:44

identified in the future it is an

play22:48

exciting research for young scientists

play22:50

because

play22:52

now the the young scientists have have

play22:55

a really powerful tool to study their

play22:57

cells and organisms of interest and

play23:00

and do genetics in a way that was not

play23:02

possible 20 25 years ago

play23:05

what is very or also interesting with

play23:09

the timeline of all those technologies

play23:11

that the

play23:13

the impact of chris parkas makes

play23:16

even more sense with regard to all the

play23:19

technologies that have developed over

play23:21

the last 15

play23:22

20 years such as high throughput

play23:24

technologies to sequence

play23:26

genomes high throughput technologies for

play23:29

screening

play23:30

for screening all the the technologies

play23:33

of

play23:34

imaging and and all the technologies

play23:37

that have largely

play23:38

evolved delivering technologies to

play23:41

deliver

play23:43

gene technologies such as crispr cas9 in

play23:46

cells and organisms

play23:47

and also new technologies that allow to

play23:50

culture

play23:51

cells and organisms that were not

play23:52

possible to culture

play23:54

15 20 years ago so this makes

play23:58

global sense and that's why i think it's

play24:00

really an

play24:01

exciting time to be able to study the

play24:04

evolution and the diversity

play24:06

of the world another message that i

play24:10

would like to

play24:11

to provide as well is that as a matter

play24:13

of fact

play24:14

uh chris parkas9 originates from

play24:17

research done on bacteria and viruses

play24:19

and we do know in our days how

play24:22

important it is to really maintain the

play24:26

research

play24:27

in macrobiology to maintain the

play24:29

expertise and to study more

play24:31

bacteria and viruses not only because

play24:34

they can cause diseases and

play24:36

and and we need to find new treatments

play24:39

for those infectious diseases but also

play24:42

because

play24:43

the last 50 years have shown to which

play24:45

extent bacterium viruses are

play24:47

really a valuable source for the

play24:49

development of novel

play24:51

biotechnologies i would like to

play24:56

thank surely the people who have done

play24:59

the work

play25:00

this work would not have been possible

play25:02

without

play25:04

young scientists being extremely

play25:07

committed

play25:08

and extremely enthusiastic the work from

play25:12

my

play25:13

side started in vienna

play25:16

at the max birds labs at the university

play25:18

of vienna

play25:19

the main part was don when i was a

play25:21

principal investigator at the

play25:23

laboratory for molecular infection

play25:24

medicine in sweden at umeo

play25:26

university i would like to thank a

play25:30

number of people but i would like to

play25:31

mention maya eckert who

play25:33

was a postdoc in my lab in vienna

play25:36

identifying

play25:37

tracer rna christoph schielinski and

play25:40

eliza delcheva

play25:41

who have been key students driving the

play25:45

project forward

play25:46

i would like to thank my collaborators

play25:48

eugenie kunin

play25:49

makarova cynthia sharma jorg vogel

play25:51

martin inec

play25:53

and charlie jennifer donna my

play25:55

co-laureate

play25:56

this was a great time this research

play25:59

developed within

play26:00

five years of time at least from my lab

play26:03

and i

play26:03

really enjoy this exciting time working

play26:07

with

play26:08

wonderful collaborators i would like

play26:10

also to take the opportunity to thank

play26:12

all my former and lab

play26:14

members who have worked with me

play26:17

the last 18 years in australia sweden

play26:21

and germany

play26:23

it has always been a pleasure to work

play26:25

with young scientists and this is also

play26:27

the reason why i like to do

play26:29

science and last but not least i would

play26:32

like to thank

play26:33

my family my friends rodger novak

play26:37

and all my colleagues who have supported

play26:40

my work and who have helped me during my

play26:43

career and i would like to thank you for

play26:45

your attention

play26:53

you

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