Nobel Lecture: Emmanuelle Charpentier, Nobel Prize in Chemistry 2020
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
🏆 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。
🔬 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。
🛡️ 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。
🧬 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。
🌐 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。
🙌 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
💡ゲノム編集
💡ノーベル賞
💡細菌
💡遺伝子変異
💡RNA
💡免疫系
💡プログラム性
💡遺伝子治療
💡多能性
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
was born
in 1968 in chevy cesaros
in france she obtained her phd
in 1995 from institute pasteur
in paris and for part of her career she
worked
at umeo university in sweden
she is now director of the max planck
unit
for the science of pathogens in berlin
germany
i now welcome you onto the stage we are
very much looking forward to hearing
your lecture
dear ladies and gentlemen i am delighted
to welcome you to my
nobel lecture it is the greatest
honor to be awarded together with
jennifer darner the nobel prize in
chemistry for the year 2020 for the
development of a method for genome
editing i would like to warmly
thank the members of the royal swedish
academy
of sciences the members of the nobel
committee and all scientists
who have supported our nomination
i wish we'll be able to give the lecture
live
unfortunately it is a recorded lecture
but i hope you will
enjoy the recording
i would like to start with explaining
you the crispr cas9 technology that
is this novel method for genome editing
so over the years all biologists have
been
extremely interested in always using
genetics to understand the functions of
genes and
we're always in need of precise genetics
that allows to recognize sites
specifically
dna of genomes of cells and organisms
and allows to modify genes and their
expression and this is what the crispr
cas9 technology does
the particularity of this technology is
that it's a
sophisticated technology yet very simple
versatile it works very efficiently and
it is composed of
an protein component called cas9 that is
represented on this slide as scissors
this protein casino
has the ability to recognize such
specifically a certain sequence
on the dna certain sequence of interest
has the ability to cleave
the dna and this cas9 protein is
programmed by the help of an
rna component that allows to bring
kas9 to the site of interest so this is
a technology that has
largely been adopted by the scientific
community
and has become very popular since the
start of its
discovery in 2012. so i would like to
actually explain you also
why this technology is transformative
so the field of genetics started in the
19th century up to the
mid-20th century whereby rules for
fundamental genetics
were established with the dna that was
isolated the dna that was shown to be
the carrier of information
and then the genetic code that was
deciphered
over the last years in the 60s
the last 50 years have witnessed the
large development of
of a number of technologies actually
all originating from research done on
bacteria
and and viruses and this started in the
70s
with different types of enzymes and
technologies that would allow to
recombine dna to clone dna to sequence
dna amplified dna
target genes and their expression
the zinc finger and tannin nucleuses
that were discovered
over the last 20 years allowing precise
genetics the same that what chris
barcas9 does
except that chris parkas9 brings a level
of programmability and a level of
of simplicity and versatility that is
quite unique
so we are all very happy because we can
now
study cells and organisms that were
difficult to study prior to chris
barcas9
the research on chris pakistan
originates in
in my love from our interest in
understanding
how streptococcus powderiness causes
diseases in humans so streptococcus
biogenes belongs to the class of
gram-positive
bacteria such as listeria and
staphylococci
this bacteria have been the main focus
of my
research during my career
i have always been interested in
understanding
how bacteria interact with their
environment so in principle the human
host
how they can cause diseases how they can
adapt to their environment
survive in the human host and also to a
certain extent how the human host can
defend itself against bacterial
infections
so the focus was always on regulatory
mechanisms
that use proteins and small rnas
the family of small rnas it's an
interesting
family of regulatory elements
which we started to work on at the
beginning of
2000 so about 20 years ago
and this research always was
mixed with always a
need to develop gene technologies along
the way
just to be able to study better those
mechanisms in bacteria
specifically in the context of their
interactions with the human host
and during my my years as a phds and
postdocs i was
certainly and decapped by the
the the non-possibility to perform
genetics in human cells which
is really the are the hosts for this
strict human pathogens so i have
developed genetic tools in bacteria i
have also worked on transgenic mice
coming back to understanding the
interaction between bacteria and the
human host and understanding as well
that there was a
lack of tools that would allow to
perform precise genetics in
in human cells for example in this this
is what chris park castleman can
can do the
the field of of small rnas has largely
evolved the last 30 years and this was a
discovery that
rna molecules in addition to b messenger
rna
or transfer rna or ribosomal rnas and
being involved in
in the transcription of the dna into a
translation into
proteins that rnas had also regulatory
functions and would be able to interact
with messenger rna molecules and also
with proteins
and regulate the expression of genes
what was not identified at the let's say
about 10-15 years ago
these were small rnas that would have
the ability to
to change gene expression by interacting
directly
with dna we were working on some small
regulatory rnas
we published some data showing that
some of these small regulatory rnas had
the ability to
change the expression of virulence
factors in bacteria so contributed a lot
to the adaptation of bacteria to their
environment
and we decided in about 15 years ago
to start a search for additional
regulatory
rnas we found a number of those rnas and
we particularly picked an rna and that
is
known as tracer rna because this rna was
very well
expressed in in bacterial cells and you
can see the gel that is a northern blood
analysis showing the
the expression of these rnas as
different forms
in in streptococcus biogenes
we had found a target for this small
regulatory rna so initially we thought
that it would have a role in
regulating the expression of the
variance factor and we had difficulties
to make sense of this
interaction but what was clear is that
at least this
rna was encoded in the vicinity of a
gene that was annotated to be a gene
including a protein that is uh
was crispr related protein containing
two nucleus domains so
a crispr protein that would have the
ability to cleave
nucleic acids so this was the start of
none nevertheless continuing our
research on tracer rna
but also working on crispr
so crispr is to be
seen and and considered as part of
of different systems which bacteria and
archaea
have evolved over millions of years
so back then archaea can be infected by
viruses as we can be
infected by viruses and bacteria and
have evolved
diverse immune systems that allow them
to cope with
the invasion of genetic elements
such as viral elements but also other
elements such as plasmins and
transposons
and this really actually is important
and to be seen in the context of of the
fitness of the bacteria with their
environment and the evolution
of of the microorganisms so here on this
slide you can see
a phage that is infecting a bacterial
cell
with the genomic component of
of the phage that is injected into the
bacterial cell
the genomes of of the virus that can
replicate
and then you have the formation of our
particles
that can uh lies back to our cells and
propagate
to lies further back to ourselves so
here we deal with phages viruses that
can kill bacterial cells and surely
the the the need for bacteria to have
evolved system that
allow to uh to defend themselves
against deaths so what is interesting is
that some of these
immune systems have been developed over
the years
as genetic tools so for example
restriction enzymes are
originally actually
different systems existing in in
bacteria
crispr is is unique in the sense that
it is an adaptive immune system there is
a first step of
of recognition that leads to the to the
immunity and it is composed of
protein components the cast proteins and
rna components the crispr
rna so i do not have the time to
go very deeply into the history of
of the chris parkas research however i
would like to mention
that uh this has involved a number of
scientists who have really performed
a pioneer work on chris barcas i have
read
all the the publications on chris parkas
when we started to work on
on the crisper cast 9 system in my lab
and this has
this is really by reading all those
articles that
that it allowed me to to really
understand what would be different of
the chris
cas9 system compared to other krispaka
systems that were
studied by my colleagues but in brief
the the crispr components are
such that the first identification where
the repeats of the crispr array so
the crispr array is formed by very short
sequences
that are identical to one another that
forms
repeats and that are interspaced by
sequences
that have as origin mobile genetic
elements this crispr array was shown to
be able to
be transcribed into rna molecules of
different sizes so probably
maturation events taking place to
activate
those crispr rna molecules in the
vicinity of the crispr array
you have the crispr associated genes
that encode the crispr associated
proteins and and very fast as well there
was
the observation that these crispr
associated proteins
contain domains that are homologous
to domains contained in proteins that
have the ability to
target dna target rna and also cleave
dna
and cleave rna so all together the idea
was that
these crispr systems would be obviously
adaptive immune systems in bacteria and
archaea
that was shown experimentally later on
in streptococcustomophilus
but that also those those
systems were identified as prokaryotic
rna interference systems by analogy to
rna interference systems
so when we started uh the research
the dogma was that there would be a
crisp complex of crispr associated
proteins that will be formed
and that will associate to the crispr
rna
to act as a machinery that would allow
to target the dna or the rna
so the way it works is as follows
the system is adaptive in the sense that
the bacteria are
first to recognize the virus and
will have the ability to memorize the
infection
by the virus and this is the way it is
done
so the virus will inject its its dna
into the bacterial cell
the chris parker system will be able to
recognize
the invading dna cleave
a certain sequence of of the invading
dna and insert
this sequence into the crispr array and
this is working as a kind of
memorization
of the virus and then you will have
expression
at the rna level of these memorized
elements of viral infections
the crispr rnas will associate with a
complex of crispr associated
proteins and those rnas allowing to
guide the crispr associated proteins
to the the invading dna of the virus
upon a second infection
and this is the way it works and there
will be recognition of the virus and one
protein of the chris barkas system will
ultimately cleave the invading dna
and the dna cannot replicate and this is
a dead end for for the virus
so this is globally uh how it works
um in streptococcus pargenes we were
lucky enough
to uh have on on on the genome of
streptococcus pyrogenes
genes that were belonging to a certain
type of chris parker system that was not
studied yet at least at the molecular
level
what the the groups of of of
the crisper casing system was really uh
in streptococcus
thermophilus uh implying uh
involving one crispr associated protein
cas9 that will be involved in
in the recognition of the virus upon
second infection but the molecular
mechanism
was not described and this is what we
started in in our lab so
we and decided to look at
the the question whether tracer rna
would actually have a regulatory role on
the chris parker system
and this is what we found what we found
is that tracer rna
contains an anti-repeat sequence that
allows it
to base pair with the repeats
of the crispr rnas and this duplex of
rna
is actually stabilized by the protein
cas9
then following this this
is going to be maturated by enzymes and
in the bacter specifically the the rnas
three and further are rnases that will
lead to the mature form
of the duplex of rna still bound to the
protein casino
then this complex of cas9
guided by the duplex of rna will be able
to recognize
specifically the dna and cleave the dna
using two nuclease domains and cleave
the dna in
a sequence specific manner so this is
what we have shown
uh seeing right away that the system
from streptococcus biogenes was
working very efficiently with cleavages
that were
as those we were expecting
and now with regard to the
programmability of
of the system the idea was to simplify
this duplex of rna and fuse those two
rnas to have a single guard rna
that would be the programmable element
of the crispr casting system so bringing
simplicity
for the design of the technology one
thing that is important to mention is
that
the the mechanism is very sophisticated
in the sense that
the ability to use two nucleus domains
to cleave the dna
and this programmability allowed to
develop
the cas9 technology further into a
technology
that can really perform multiple
modifications
on on the genome so it can
correct mutations introduce
new mutations on the dna it can allow to
delete genes delete certain sequences of
dna
add new sequences of dna at the site of
interest
replace genes by other genes and over
the last
eight years a number of scientists and
developers
have really put forward the technology
to really have the technology
evolving in multiple versions that allow
to do some multiplexing
and that really allow to perform precise
genetics in an unprecedented
manner very fast actually scientists
adopted this this technology and showed
in a very very short amount of time that
the technology was efficient
to act on on the dna and modify genes
and their expression
in a variety of cells including human
cells
in organoids in modal organisms such as
mice fish
fly and also plants so a very
transformative
technology i do not have for sure the
time to explain you all the details of
the science beyond
behind the crispr castline system but
chris parkas is a largely evolving
system
all the chris barker systems including
crisper cas9
and this is early on the diversity
of this system that we understood
what would be conserved and what will be
the basis of the mechanism so release
this cas9 protein
guided by a duplex of rna and that could
be
among all the different crispr systems
existing
that will be the system minimal enough
to
harness as a powerful gene technology
and this is quite amazing how the
the systems have evolved they have
evolved surely in multiple
other systems than the crispr castline
system now we have
two classes identified and within
each of the class multiple systems and
subsystems so since chris parkas9
other minimal systems have been
identified
further developed also as chris parkas
technologies so enlarging the chris
podcast toolbox
you have large applications for this
genome editing
technology so for sure for to understand
better mechanisms of of life so it's
very useful for fundamental research
to unravel novel molecules novel
pathways
to be able to really work with the
the cells and organisms that are of
interest
for clinical purposes the technology has
been also
uh very well developed with regard to
the applications in understanding better
the mechanisms of of life sciences in
modern organisms
such as mice drosophila and and fish
it has also been a game changer for
allowing precise genetics in plants
and it has large applications in
medicine either directly
or indirectly by
allowing to develop better models of
diseases
and also by allowing to develop the
crispr cas9 technology as a direct
tool for really
to work as a gene medicine and
use the technology directly to treat
certain types of
of diseases such as human genetic
disorders
or certain cancers by combining
the crispr cas9 technology with
immunotherapy it's also
very transformative in the field of
plant biology
with the production of plant crops
surely with ethical considerations
that have to be taken into account
what next so surely the crispr
biologists continued to to work on this
field
continue to identify novel chris parker
systems
thanks to the sequencing of novel
genomes of
of bacterial species and rkr species
recently novel defense systems in
bacteria and
archaea have been identified and and
this will continue so
we can expect from research on on
microbes
to have further genetic technologies to
be
identified in the future it is an
exciting research for young scientists
because
now the the young scientists have have
a really powerful tool to study their
cells and organisms of interest and
and do genetics in a way that was not
possible 20 25 years ago
what is very or also interesting with
the timeline of all those technologies
that the
the impact of chris parkas makes
even more sense with regard to all the
technologies that have developed over
the last 15
20 years such as high throughput
technologies to sequence
genomes high throughput technologies for
screening
for screening all the the technologies
of
imaging and and all the technologies
that have largely
evolved delivering technologies to
deliver
gene technologies such as crispr cas9 in
cells and organisms
and also new technologies that allow to
culture
cells and organisms that were not
possible to culture
15 20 years ago so this makes
global sense and that's why i think it's
really an
exciting time to be able to study the
evolution and the diversity
of the world another message that i
would like to
to provide as well is that as a matter
of fact
uh chris parkas9 originates from
research done on bacteria and viruses
and we do know in our days how
important it is to really maintain the
research
in macrobiology to maintain the
expertise and to study more
bacteria and viruses not only because
they can cause diseases and
and and we need to find new treatments
for those infectious diseases but also
because
the last 50 years have shown to which
extent bacterium viruses are
really a valuable source for the
development of novel
biotechnologies i would like to
thank surely the people who have done
the work
this work would not have been possible
without
young scientists being extremely
committed
and extremely enthusiastic the work from
my
side started in vienna
at the max birds labs at the university
of vienna
the main part was don when i was a
principal investigator at the
laboratory for molecular infection
medicine in sweden at umeo
university i would like to thank a
number of people but i would like to
mention maya eckert who
was a postdoc in my lab in vienna
identifying
tracer rna christoph schielinski and
eliza delcheva
who have been key students driving the
project forward
i would like to thank my collaborators
eugenie kunin
makarova cynthia sharma jorg vogel
martin inec
and charlie jennifer donna my
co-laureate
this was a great time this research
developed within
five years of time at least from my lab
and i
really enjoy this exciting time working
with
wonderful collaborators i would like
also to take the opportunity to thank
all my former and lab
members who have worked with me
the last 18 years in australia sweden
and germany
it has always been a pleasure to work
with young scientists and this is also
the reason why i like to do
science and last but not least i would
like to thank
my family my friends rodger novak
and all my colleagues who have supported
my work and who have helped me during my
career and i would like to thank you for
your attention
you
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