hello what do you think you’re looking
at here when you look at the screen do
you see stars and distant galaxies
perhaps as if you’re looking through a
telescope in fact you’re looking through
a microscope so what you’re seeing is a
very small sample of water taken from
the ocean and that sample has been
stained with the fluorescent dye that
lights up any DNA the color green DNA is
the blueprint of life so what you’re
seeing is life those very small green
dots in fact are viruses the ocean is
full of viruses but don’t worry these
viruses couldn’t care less about you
they’re not there to hurt you their job
is to infect bacteria which are the
larger green dots in that picture
what are bacteria well they look
something like this and maybe when you
think about them you think about
diseases like cholera or the plague or a
strep throat well just like viruses in
the world the bacteria is the back the
bacteria are everywhere excuse me and
most of them don’t care about you either
they’re not there to make you sick they
are there to live their lives happily
and freely so here’s what a bacteria
might look like if we were to draw a
cartoon of it bacteria are alive their
cells not unlike our own they have a
cell membrane and a cell wall to protect
them from the outside world some of them
even have little tails called flagella
like this one others have finger like
appendages that help them to move around
and survive in their environments on the
inside of a bacterial cell just like on
the inside of our cell is DNA the
blueprint for all life this DNA allows
bacteria to produce the proteins that it
needs to live allows it to eat food and
to avoid its enemies what a viruses look
like this is a cartoon of a virus and
again when you think of viruses perhaps
you think of the nasty ones HIV
poliovirus the flu these are the ones
we’re very concerned about but again
most viruses look something like this
and their job is to infect bacteria this
virus is not really alive it is an inert
protein shell that’s
floating around in the world looking for
a home every virus needs a home
it can’t replicate without one and in
this case that viruses home is a
bacteria inside of the head of this
lunar landing module type apparatus is
the DNA for the virus the DNA is what
unites all life on the planet so over my
career as a researcher and in my
laboratory in San Francisco we’ve been
very fascinated in the interactions
between these viruses and those bacteria
since the world is full of them were
fascinated by a very simple question how
do bacteria protect themselves from
viruses why are we so fascinated by this
question I take you back to this picture
and I hope it invokes in you a very
fundamental feeling in all of us and
that is one of basic curiosity that’s
something that unites all scientists
were fascinated by how the world works
and in my in my role how biology works
how life is living on this planet and so
we want to know how viruses and bacteria
get along with each other the second and
perhaps more tangible example here is
that bacterial viruses are very good at
doing one thing and that is killing
bacteria and in this era we are in
trouble we are risking running out of
antibiotics to use to treat bacterial
infections so in my laboratory and in
many others around the world we look to
nature where we find bacterial viruses
that can teach us how we can kill
bacteria better that’s a big goal for my
lab and the last point I’ll share with
you today is how studying the
interactions between viruses and
bacteria have generated tools that
scientists desperately need and I’m not
talking about hammers and nails I’m
talking about molecular tools that allow
us to alter the DNA of living organisms
so we can study them learn from them and
cure disease so this first point basic
curiosity I hope this picture of a girl
looking through a magnifying glass
brings you back to a time when you were
a child who was fascinated with how the
world worked whether it was looking at
Iraq or collecting frogs from a local
pond this is something that I think we
all share at a fundamental level and as
scientists we like to look at things too
here is a picture I took as a grad
to a student using an electron
microscope where I was able to zoom in
on the world at a hundred thousand times
and I’m showing you a picture of the
bacterial viruses we study again they
have a head full of DNA and a tail that
they inject that DNA through we can look
even closer we can see DNA the DNA
that’s inside of that virus’s head but
we don’t really like to look at DNA we
like to sequence it you may be familiar
with the a C’s T’s and G’s that make up
our DNA and the DNA of everything on the
planet that sequence is the blueprint
scientists love sequencing DNA because
it gives us the basic building blocks of
life and it allows us all to talk to
each other whether you’re studying
viruses or bacteria or humans they’ve
all got DNA and that DNA has a job to
code for the production of amino acids
that are strung together and make
proteins like the one shown here
three-dimensional machines that are what
make our cells function what make
bacterial cells function and what makes
viruses function so once we understand
these basic building blocks of life we
can manipulate and study them and learn
from them the second point I want to
make is bacterial viruses are very good
at killing bacteria here’s an example of
one that in my laboratory we work on day
and night called Pseudomonas aeruginosa
the World Health Organization has told
us that it is the number two organism on
the list of bacterial pathogens that we
desperately need new antibiotics for
this is a drug-resistant bacteria that
infects people with cystic fibrosis as
well as burn wounds in my lab we study
viruses that kill this particular
bacteria and we hope to learn how they
do that and one day we may be better
able to engineer strategies to kill this
bacteria and many other drug-resistant
like it okay so what do we actually do
we have the basic building blocks we
have a goal in mind which is to learn
how to kill bacteria and then we return
to this question who wins the battle
when a virus and the bacteria bump into
each other does the virus win and kill
the bacteria or it is the bacteria win
and go on surviving and living its life
so what happens normally a virus
attaches to a bacterial cell like shown
here the DNA from the head
goes through the tail into the bacteria
and this virus has one goal it’s to
replicate to very high numbers inside of
its host and burst it open killing the
bacteria of producing about a hundred
new progeny viruses to go on in the
environment and find a new home about
ten years ago researchers made an
amazing discovery that changed how we
view this process that discovery is
called CRISPR CRISPR is an immune system
that bacteria have against viruses just
like we make antibodies against viruses
bacteria used CRISPR what is CRISPR
exactly well you heard you heard from
Jennifer Doudna that this is basically a
memory it’s a vaccinated mugshot the
CRISPR system has seen this virus before
and what it does just like this little
pac-man inside of the cell it’s waiting
for the virus DNA to come through that
tail of the virus and it’s going to chew
it up that’s what CRISPR does in nature
CRISPR is programmed to kill bacterial
viruses and to up their DNA as a
graduate student
Iko discovered the next layer in this
battle I discovered anti CRISPR proteins
so the viruses are not passive they
don’t want to let their DNA get chewed
up by the CRISPR pac-man inside of the
cell they want to stop it so of course
what do they do
the viruses encode a very small protein
like a wedge that they can throw into
pac-man’s mouth we call that the anti
CRISPR what does this enable well it
enables the virus to do exactly what it
wants to do it turns off the CRISPR
machine and it replicates to high
numbers and it breaks open the bacteria
and importantly it kills the bacteria
this is what we want we want to
understand how viruses kill bacteria and
CRISPR could stand in our way because it
stops viruses so the discovery of anti
crispers allows us to make better
viruses and allows us to kill deadly
bacteria
with the last part of my talk I wanted
to tell you more about the tools
scientists need tools you may know that
in every cell of your body you have 3
billion letters of DNA 3 billion a C’s
GS and T’s and I told you earlier that
were powered by curiosity we’ve
sequenced the human genome we know those
a C’s T’s and G’s but for a long time we
were relegated to only being able to
look we couldn’t fix
for example cystic fibrosis is caused by
a single mutation we know where that
mutation is in the in the 3 billion
letters of people with cystic fibrosis
we can say that’s where your mutation is
and then you might say well could you
change it the answer had been no until
now by studying the arms race between
viruses and bacteria CRISPR has provided
us with such a tool let me show you what
it looks like
CRISPR Castine is the real name for the
tool and cast night is a protein it’s a
molecular machine that lives inside of
bacterial cells normally and how the
bacteria programs it is by this purple
sequence here that purple RNA a cousin
of DNA allows cast 9 to locate with
precision any DNA sequence that matches
it and just like that pac-man these
scissors enable the cutting of the DNA
sequence now imagine how challenging
this must be we have 3 billion letters
in our DNA we program cast 9 in the lab
literally on the computer we tell it
what to cut and we give it 20 letters it
can serve a 3 billion letters and find
20 and cut with remarkable precision
so on the next slide I want to show you
what cast 9 really looks like of course
it doesn’t look like this this cartoon
what you’re looking at here is a
structure of cast 9 what that means is
every little gray blob on this screen is
a carbon or oxygen or hydrogen atom this
is an atomic structure basically a
picture taken with one of the most
powerful microscopes on the planet and
inside of it is that orange guide
sequence the RNA that tells cast 9 where
go and what to cut in purple is the
target DNA that it has found and it’s
going to cut that DNA however cast nine
is not perfect you might imagine in
those three billion letters where we’re
asking it to find just 20 that it might
make a mistake every now and then and it
does we it cuts and can introduce a
mutation in places where we don’t want
scientists around the world are working
to solve this problem and I guarantee
you the problem will be solved our
strategy is to go back to that virus and
bacterial arms race to learn how does
the natural world solve this problem how
can we stop cast 9 from looking around
ourselves and cutting at the wrong place
well the answer to us is clear we can
turn it off how could we possibly turn
off cast 9 we do it with an anti CRISPR
the same protein that the viruses use to
stop cast 9 in the wild can be used in
human cells so when we decide that cast
9 has done its job and fixed the
mutation we want it to fix we can turn
it off before it has the chance to make
any mistakes the red protein shown there
is where the anti CRISPR protein binds
it’s very small but it’s very smart it
binds in a very precise location on that
cast 9 protein and turns it off this
structure was solved by a collaborator
of mine who goes on in Jennifer Doudna
‘z lab at the University of California
Berkeley a lab that has led the charge
on developing as CRISPR casts 9
technology so to summarize my
presentation I want to take you back to
this picture I hope it inspires in you
the sort of wonder that we feel in my
laboratory when we think about viruses
and bacteria in the natural world where
they exist in the oceans in the soil and
even in and on your body right now a
molecular arms race is raging between
the bacteria and the viruses that live
on your skin and in your gut it’s really
quite remarkable and so this is what
powers us everyday is the basic
curiosity to try to understand how this
works but also to understand how we can
turn this into a useful tool to kill
bacterial viruses
and I told you today as well how
scientists need tools to enable the
engineering of human cells not
necessarily for designer babies but
secure genetic diseases that is the
focus of the CRISPR cast line community
and I’ve told you how first CRISPR cast
9 came from this natural arms race and
we’ve went back to the arms race to
identify bacterial viruses that produce
anti CRISPR proteins that stop Castine
from cutting where we don’t want it to
and we think this will enable precise
and safe gene editing going forward
thank you
[Applause]
you
at here when you look at the screen do
you see stars and distant galaxies
perhaps as if you’re looking through a
telescope in fact you’re looking through
a microscope so what you’re seeing is a
very small sample of water taken from
the ocean and that sample has been
stained with the fluorescent dye that
lights up any DNA the color green DNA is
the blueprint of life so what you’re
seeing is life those very small green
dots in fact are viruses the ocean is
full of viruses but don’t worry these
viruses couldn’t care less about you
they’re not there to hurt you their job
is to infect bacteria which are the
larger green dots in that picture
what are bacteria well they look
something like this and maybe when you
think about them you think about
diseases like cholera or the plague or a
strep throat well just like viruses in
the world the bacteria is the back the
bacteria are everywhere excuse me and
most of them don’t care about you either
they’re not there to make you sick they
are there to live their lives happily
and freely so here’s what a bacteria
might look like if we were to draw a
cartoon of it bacteria are alive their
cells not unlike our own they have a
cell membrane and a cell wall to protect
them from the outside world some of them
even have little tails called flagella
like this one others have finger like
appendages that help them to move around
and survive in their environments on the
inside of a bacterial cell just like on
the inside of our cell is DNA the
blueprint for all life this DNA allows
bacteria to produce the proteins that it
needs to live allows it to eat food and
to avoid its enemies what a viruses look
like this is a cartoon of a virus and
again when you think of viruses perhaps
you think of the nasty ones HIV
poliovirus the flu these are the ones
we’re very concerned about but again
most viruses look something like this
and their job is to infect bacteria this
virus is not really alive it is an inert
protein shell that’s
floating around in the world looking for
a home every virus needs a home
it can’t replicate without one and in
this case that viruses home is a
bacteria inside of the head of this
lunar landing module type apparatus is
the DNA for the virus the DNA is what
unites all life on the planet so over my
career as a researcher and in my
laboratory in San Francisco we’ve been
very fascinated in the interactions
between these viruses and those bacteria
since the world is full of them were
fascinated by a very simple question how
do bacteria protect themselves from
viruses why are we so fascinated by this
question I take you back to this picture
and I hope it invokes in you a very
fundamental feeling in all of us and
that is one of basic curiosity that’s
something that unites all scientists
were fascinated by how the world works
and in my in my role how biology works
how life is living on this planet and so
we want to know how viruses and bacteria
get along with each other the second and
perhaps more tangible example here is
that bacterial viruses are very good at
doing one thing and that is killing
bacteria and in this era we are in
trouble we are risking running out of
antibiotics to use to treat bacterial
infections so in my laboratory and in
many others around the world we look to
nature where we find bacterial viruses
that can teach us how we can kill
bacteria better that’s a big goal for my
lab and the last point I’ll share with
you today is how studying the
interactions between viruses and
bacteria have generated tools that
scientists desperately need and I’m not
talking about hammers and nails I’m
talking about molecular tools that allow
us to alter the DNA of living organisms
so we can study them learn from them and
cure disease so this first point basic
curiosity I hope this picture of a girl
looking through a magnifying glass
brings you back to a time when you were
a child who was fascinated with how the
world worked whether it was looking at
Iraq or collecting frogs from a local
pond this is something that I think we
all share at a fundamental level and as
scientists we like to look at things too
here is a picture I took as a grad
to a student using an electron
microscope where I was able to zoom in
on the world at a hundred thousand times
and I’m showing you a picture of the
bacterial viruses we study again they
have a head full of DNA and a tail that
they inject that DNA through we can look
even closer we can see DNA the DNA
that’s inside of that virus’s head but
we don’t really like to look at DNA we
like to sequence it you may be familiar
with the a C’s T’s and G’s that make up
our DNA and the DNA of everything on the
planet that sequence is the blueprint
scientists love sequencing DNA because
it gives us the basic building blocks of
life and it allows us all to talk to
each other whether you’re studying
viruses or bacteria or humans they’ve
all got DNA and that DNA has a job to
code for the production of amino acids
that are strung together and make
proteins like the one shown here
three-dimensional machines that are what
make our cells function what make
bacterial cells function and what makes
viruses function so once we understand
these basic building blocks of life we
can manipulate and study them and learn
from them the second point I want to
make is bacterial viruses are very good
at killing bacteria here’s an example of
one that in my laboratory we work on day
and night called Pseudomonas aeruginosa
the World Health Organization has told
us that it is the number two organism on
the list of bacterial pathogens that we
desperately need new antibiotics for
this is a drug-resistant bacteria that
infects people with cystic fibrosis as
well as burn wounds in my lab we study
viruses that kill this particular
bacteria and we hope to learn how they
do that and one day we may be better
able to engineer strategies to kill this
bacteria and many other drug-resistant
like it okay so what do we actually do
we have the basic building blocks we
have a goal in mind which is to learn
how to kill bacteria and then we return
to this question who wins the battle
when a virus and the bacteria bump into
each other does the virus win and kill
the bacteria or it is the bacteria win
and go on surviving and living its life
so what happens normally a virus
attaches to a bacterial cell like shown
here the DNA from the head
goes through the tail into the bacteria
and this virus has one goal it’s to
replicate to very high numbers inside of
its host and burst it open killing the
bacteria of producing about a hundred
new progeny viruses to go on in the
environment and find a new home about
ten years ago researchers made an
amazing discovery that changed how we
view this process that discovery is
called CRISPR CRISPR is an immune system
that bacteria have against viruses just
like we make antibodies against viruses
bacteria used CRISPR what is CRISPR
exactly well you heard you heard from
Jennifer Doudna that this is basically a
memory it’s a vaccinated mugshot the
CRISPR system has seen this virus before
and what it does just like this little
pac-man inside of the cell it’s waiting
for the virus DNA to come through that
tail of the virus and it’s going to chew
it up that’s what CRISPR does in nature
CRISPR is programmed to kill bacterial
viruses and to up their DNA as a
graduate student
Iko discovered the next layer in this
battle I discovered anti CRISPR proteins
so the viruses are not passive they
don’t want to let their DNA get chewed
up by the CRISPR pac-man inside of the
cell they want to stop it so of course
what do they do
the viruses encode a very small protein
like a wedge that they can throw into
pac-man’s mouth we call that the anti
CRISPR what does this enable well it
enables the virus to do exactly what it
wants to do it turns off the CRISPR
machine and it replicates to high
numbers and it breaks open the bacteria
and importantly it kills the bacteria
this is what we want we want to
understand how viruses kill bacteria and
CRISPR could stand in our way because it
stops viruses so the discovery of anti
crispers allows us to make better
viruses and allows us to kill deadly
bacteria
with the last part of my talk I wanted
to tell you more about the tools
scientists need tools you may know that
in every cell of your body you have 3
billion letters of DNA 3 billion a C’s
GS and T’s and I told you earlier that
were powered by curiosity we’ve
sequenced the human genome we know those
a C’s T’s and G’s but for a long time we
were relegated to only being able to
look we couldn’t fix
for example cystic fibrosis is caused by
a single mutation we know where that
mutation is in the in the 3 billion
letters of people with cystic fibrosis
we can say that’s where your mutation is
and then you might say well could you
change it the answer had been no until
now by studying the arms race between
viruses and bacteria CRISPR has provided
us with such a tool let me show you what
it looks like
CRISPR Castine is the real name for the
tool and cast night is a protein it’s a
molecular machine that lives inside of
bacterial cells normally and how the
bacteria programs it is by this purple
sequence here that purple RNA a cousin
of DNA allows cast 9 to locate with
precision any DNA sequence that matches
it and just like that pac-man these
scissors enable the cutting of the DNA
sequence now imagine how challenging
this must be we have 3 billion letters
in our DNA we program cast 9 in the lab
literally on the computer we tell it
what to cut and we give it 20 letters it
can serve a 3 billion letters and find
20 and cut with remarkable precision
so on the next slide I want to show you
what cast 9 really looks like of course
it doesn’t look like this this cartoon
what you’re looking at here is a
structure of cast 9 what that means is
every little gray blob on this screen is
a carbon or oxygen or hydrogen atom this
is an atomic structure basically a
picture taken with one of the most
powerful microscopes on the planet and
inside of it is that orange guide
sequence the RNA that tells cast 9 where
go and what to cut in purple is the
target DNA that it has found and it’s
going to cut that DNA however cast nine
is not perfect you might imagine in
those three billion letters where we’re
asking it to find just 20 that it might
make a mistake every now and then and it
does we it cuts and can introduce a
mutation in places where we don’t want
scientists around the world are working
to solve this problem and I guarantee
you the problem will be solved our
strategy is to go back to that virus and
bacterial arms race to learn how does
the natural world solve this problem how
can we stop cast 9 from looking around
ourselves and cutting at the wrong place
well the answer to us is clear we can
turn it off how could we possibly turn
off cast 9 we do it with an anti CRISPR
the same protein that the viruses use to
stop cast 9 in the wild can be used in
human cells so when we decide that cast
9 has done its job and fixed the
mutation we want it to fix we can turn
it off before it has the chance to make
any mistakes the red protein shown there
is where the anti CRISPR protein binds
it’s very small but it’s very smart it
binds in a very precise location on that
cast 9 protein and turns it off this
structure was solved by a collaborator
of mine who goes on in Jennifer Doudna
‘z lab at the University of California
Berkeley a lab that has led the charge
on developing as CRISPR casts 9
technology so to summarize my
presentation I want to take you back to
this picture I hope it inspires in you
the sort of wonder that we feel in my
laboratory when we think about viruses
and bacteria in the natural world where
they exist in the oceans in the soil and
even in and on your body right now a
molecular arms race is raging between
the bacteria and the viruses that live
on your skin and in your gut it’s really
quite remarkable and so this is what
powers us everyday is the basic
curiosity to try to understand how this
works but also to understand how we can
turn this into a useful tool to kill
bacterial viruses
and I told you today as well how
scientists need tools to enable the
engineering of human cells not
necessarily for designer babies but
secure genetic diseases that is the
focus of the CRISPR cast line community
and I’ve told you how first CRISPR cast
9 came from this natural arms race and
we’ve went back to the arms race to
identify bacterial viruses that produce
anti CRISPR proteins that stop Castine
from cutting where we don’t want it to
and we think this will enable precise
and safe gene editing going forward
thank you
[Applause]
you
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