[Music]
protein meant one thing to me in the
past is what you eat right and I’m
although I’m a scientist I trained as a
physicist so he came to me as a big
surprise when I learned that proteins
can do much more than just serving as
your food items here’s an example motor
protein can walk on a cellular highway
to carry a cargo down your nerve from
the brain to the joint and the
extremities these proteins are called
the nano machines because they do
critical functions needed for all forms
of life with the precision and
efficiency that is still unmatched by
the man-made machines quite amazingly
some of the motor proteins are
responsible for how some animals change
their color I’m going to show you this
movie obtained by professor Galvan in
Northwestern University a few years back
but let me explain why should be seeing
a zebrafish has dark pigments inside the
skin cells if you pick one cell and put
it on a culture dish you can see the
cell on the surface with a dark pigment
spread all over the cell that’s why
there’s a reason why the cell appears
black now if the fish wants to change
its color it tells the motor proteins to
grab the dark pigments and move them
toward the middle of the cell okay
following the highways that I’ll lay
down sent repeatedly along the radial
direction then the dark pigments will be
concentrated in the middle of the cell
and therefore the rest of the cell area
becomes clear making the cell up here
much less dark and much brighter okay
so let me play the movie
amazing okay that’s how the fish changes
color in fact chameleons that we know
change the color in the same way just
like in more complex because of course
they are more colorful in fact if you
think about and have any question about
your body the answer always almost
always lies in the proteins how do we
sense pain there are temperature
sensitive proteins that become active at
high temperatures only causing pain and
this is important because for example
without that pain we will not remove our
hands from boiling water Chili Peppers
produce a natural compound capsaicin
capsaicin capsaicin binds to that
temperature sensing protein to lower the
minimum temperature for activation
that’s the reason why eating Chili
Peppers can cause immense pain even at
the body temperature and that’s that’s
also the reason why you can believe the
pain temporarily by drinking cold water
our DNA yes then is all the time but we
do not develop cancer normally until the
oil days because there are DNA repair
proteins that can take care of the DNA
damage we also need proteins to break
down our course and is by-product and in
East Asia many people have defects in
these proteins so you get headaches and
your face turns red even after a single
drink by now we know the identities of
many many proteins that are responsible
for abilities to think dance smell hear
and see and even fall in love okay
actually that part is not true you know
we don’t know what proteins are
underlined the log part but
I want to know at some point so they’re
probably more than 20,000 different
proteins in us or specializing in
different tasks so in that sense body is
much like the human society that has a
thousand different occupations this
analogy is a good one because if you
expand the body to the scale of the
earth then a single protein is about the
size of a single human being therefore
these proteins are only massively small
measuring just a few nanometers are
close about ten thousand times smaller
than the width of a human hair because
they are so tiny they are called another
machines and because they are so tiny it
is very difficult if not impossible and
it used to be very difficult to measure
and monitor the movements of these
proteins in real time this has however
changed because of the breathtaking
advances in single molecule fluorescence
imaging technologies nowadays we can
follow a single protein at a nanometre
precision all the way are we if
following each and every tiny step you
can put a fluorescent tag on the protein
and zap it with a laser and use a
powerful microscope to take movies we
can follow and determine how quickly a
protein moves from point A to point B we
can also determine in how many steps it
takes to reach that destination we
Carissa study how disease-causing
mutations change the proteins behavior
the feeder chip here is quite amazing
remarkable is really equivalent to using
a telescope on the surface of the Moon
to record the movements of my favorite
needs a player Roger Federer on the
surface of the earth in Wimbledon
however if your interest in learning
what makes a feather such a special
player this is not enough you need to do
better you can do better by using a
technology called single molecule Fred
Fred is a is a spectroscopic molecular
ruler that can measure changes in
distance between fluorescent molecules
of different color so when Roger here
suing his swings his racket the distance
between the two hands will change as a
function of time if we put a green dye
on the right hand and the red dye on the
left hand at the beginning in the
backswing to two molecules are very far
away from each other so when you excite
the green dye with the laser you get
green signal but once you follow through
then two hands are close to each other
and then the excitation by the later
becomes transferred to the red dye and
then you get red signal so by simply
looking at the color change you can
deduce a distance between the two hands
and they have the shape change of the
own of the protein during function so
this is like having a courtside seat
next to the Wimbledon center court and
observing what makes a federal
generational talent perhaps the best
ever now we are in Gangnam district so I
couldn’t resist the temptation to use
[Music]
whooping Gangnam style so as you can see
you can simply watch the color change
and deduce the dance moves of Si and you
can do this from far away you can do
this from the moon right by simply using
a powerful telescope to change the color
to see the color change in fact we can
now use these technologies to to see the
complicated and amazing dance movements
of many medically important proteins
such as oncogenes you know transmitter
transporters and an HIV before
transcriptase we have been doing doing
this for some years it still amazes me
every day while you can discover on a
of years back we are studying the
movement of DNA motor protein moving on
the DNA surprisingly instead of falling
off at the end of the DNA Street the
protein reappeared at the beginning of
the street and then repeated the
patrolling movements numerous times it
turns out the protein uses this
patrolling function to safeguard the
street from other proteins that can
potentially cause genomic damage because
extensive genomic damage can lead to
cancer and human development we now must
view these proteins as the superheroes
that keeps the threat of cancer at bay
that’s my heel okay in fact and if there
is a mutation in one of these human
resisting proteins that can lead to a
real problem for example just the six
letters change in a gene called breast
cancer susceptibility gene – also known
as bracha – if you have the mutation
then your chance of getting a breast
cancer
or ovarian cancer increases dramatically
famously the actress Angelina Jolie
surgically removed her organs because of
the broad commutations wouldn’t it be
amazing wonderful if instead we can
remove the disease causing mutations
from the genome altogether this dream
may become a reality soon because of the
technology called CRISPR and it may not
be to find the future when until we can
cut out a defective a portion of a gene
and replace it with a functional normal
copy in CRISPR technology for gene
editing there is a protein called test
nine that binds DNA and unwise a DNA to
examine the sequence if there’s a great
sequence match that CRISPR cast nine
custardy na to start genome editing
basically case nine protein is asking
the DNA are you my true partner before
making a commitment this technology
works wide enough to a triple the yield
of tomato plants without having to name
it at GMO
that’s because tomato genes can be
precisely edited without introducing a
gene from a different species you can
also use a crisp focus on technology to
cure mice of deafness causing mutations
and there are many amazing examples that
are highly promising however there are
still major problems a major one our
organs save medical applications yes 9
does not just cut at one place with a
perfect sequence match it can also cut
sequences that are partially matching
only this is called off-target effect
and because our genome is very large 3
build 3 billion letters of DNA they can
be of a large number of
harshly magical sequences that can be
cut by cast nine unintentionally and
causing you know unpredictable
consequences now we are using single
so if the cast nine binds the DNA to
unwind it fully when the sequence
matching is great basically you get a
green signal to tell the enzyme this is
good match you can settle down
marry her whatever right if there’s no
match then then you don’t unwind the DNA
you get your a signal so far so good
now for partially matching sequences
well ideally we want to have just red
line only okay but in reality when you
measured the activities we got a mixture
of red and green and this is a reason
why test nine protein actually are often
you know enters into a commitment of a
long-term relation even with less than
an ideal match using this understanding
that we are trying to engineer test nine
proteins that can be much more accurate
without us
side effects okay so proteins and nano
machines and superheroes and that’s the
message for today I want to invite
thanking you for being here we also want
to explain our research better and also
convey the excitement and the fun aspect
of the scientific enterprise to non
scientist and also to in a young student
so I commissioned a song about our
research from a Baltimore artist in the
Maryland us where I live and I’m going
the audience demon is here yeah
SM Fred please do not forget single
molecules and dyes the colors green and
red yeah SM pray you will not regret use
cast nine to cut like it’s Gillette with
Chris protect hey
in this lab we doing work with
fluorescence study as I’m kinetic
sequence the genus fnatic yeah
ATC inches we like to play with beams
cast nine on wise the genes and then it
cuts this is a jean skirt makes
evanescent fields shows us evanescent
fields shows us my fluorescence heals
you record the videos like we got out of
lesson feels getting attracted getting
repelled measuring habits what is this
pal molecular structure molecular
chatting and everything down Amelie
another wrapping optical trap yeah pull
on the strap straps yeah optical trap
yeah move on the map hey yeah you cannot
use fret with it the fluorophores
photobleach out of it get ready to laser
it you measure by moving the stage a bit
you look at its elements you pull and
you look at the range of it you pull and
you look at the strength of it you pull
and you start rearranging it time to
talk about single molecule imaging go
faster
naturally this imaging will come with
its limiting factors you focus on part
of the slides not that the others don’t
matter
super s will come select and I’ll choose
a variety
son Fred please do not forget don’t
single molecules and dyes the colors
better right yeah SM pray you will not
regret use guys night to cut like you
fill it with hay housing base pairs
without stop it splits your defense like
it scary when it’s walking here at TEDx
reven rep X cuz its new tech are fueling
case and Watson to flex we use friend
what spread the donors and acceptors you
split the channel like you splitting
into sectors the closer to dies the
higher the fret the further they go the
lower the red the green is the donor the
res acceptor reading the data like
reading the leash like reading the letters
protein meant one thing to me in the
past is what you eat right and I’m
although I’m a scientist I trained as a
physicist so he came to me as a big
surprise when I learned that proteins
can do much more than just serving as
your food items here’s an example motor
protein can walk on a cellular highway
to carry a cargo down your nerve from
the brain to the joint and the
extremities these proteins are called
the nano machines because they do
critical functions needed for all forms
of life with the precision and
efficiency that is still unmatched by
the man-made machines quite amazingly
some of the motor proteins are
responsible for how some animals change
their color I’m going to show you this
movie obtained by professor Galvan in
Northwestern University a few years back
but let me explain why should be seeing
a zebrafish has dark pigments inside the
skin cells if you pick one cell and put
it on a culture dish you can see the
cell on the surface with a dark pigment
spread all over the cell that’s why
there’s a reason why the cell appears
black now if the fish wants to change
its color it tells the motor proteins to
grab the dark pigments and move them
toward the middle of the cell okay
following the highways that I’ll lay
down sent repeatedly along the radial
direction then the dark pigments will be
concentrated in the middle of the cell
and therefore the rest of the cell area
becomes clear making the cell up here
much less dark and much brighter okay
so let me play the movie
amazing okay that’s how the fish changes
color in fact chameleons that we know
change the color in the same way just
like in more complex because of course
they are more colorful in fact if you
think about and have any question about
your body the answer always almost
always lies in the proteins how do we
sense pain there are temperature
sensitive proteins that become active at
high temperatures only causing pain and
this is important because for example
without that pain we will not remove our
hands from boiling water Chili Peppers
produce a natural compound capsaicin
capsaicin capsaicin binds to that
temperature sensing protein to lower the
minimum temperature for activation
that’s the reason why eating Chili
Peppers can cause immense pain even at
the body temperature and that’s that’s
also the reason why you can believe the
pain temporarily by drinking cold water
our DNA yes then is all the time but we
do not develop cancer normally until the
oil days because there are DNA repair
proteins that can take care of the DNA
damage we also need proteins to break
down our course and is by-product and in
East Asia many people have defects in
these proteins so you get headaches and
your face turns red even after a single
drink by now we know the identities of
many many proteins that are responsible
for abilities to think dance smell hear
and see and even fall in love okay
actually that part is not true you know
we don’t know what proteins are
underlined the log part but
I want to know at some point so they’re
probably more than 20,000 different
proteins in us or specializing in
different tasks so in that sense body is
much like the human society that has a
thousand different occupations this
analogy is a good one because if you
expand the body to the scale of the
earth then a single protein is about the
size of a single human being therefore
these proteins are only massively small
measuring just a few nanometers are
close about ten thousand times smaller
than the width of a human hair because
they are so tiny they are called another
machines and because they are so tiny it
is very difficult if not impossible and
it used to be very difficult to measure
and monitor the movements of these
proteins in real time this has however
changed because of the breathtaking
advances in single molecule fluorescence
imaging technologies nowadays we can
follow a single protein at a nanometre
precision all the way are we if
following each and every tiny step you
can put a fluorescent tag on the protein
and zap it with a laser and use a
powerful microscope to take movies we
can follow and determine how quickly a
protein moves from point A to point B we
can also determine in how many steps it
takes to reach that destination we
Carissa study how disease-causing
mutations change the proteins behavior
the feeder chip here is quite amazing
remarkable is really equivalent to using
a telescope on the surface of the Moon
to record the movements of my favorite
needs a player Roger Federer on the
surface of the earth in Wimbledon
however if your interest in learning
what makes a feather such a special
player this is not enough you need to do
better you can do better by using a
technology called single molecule Fred
Fred is a is a spectroscopic molecular
ruler that can measure changes in
distance between fluorescent molecules
of different color so when Roger here
suing his swings his racket the distance
between the two hands will change as a
function of time if we put a green dye
on the right hand and the red dye on the
left hand at the beginning in the
backswing to two molecules are very far
away from each other so when you excite
the green dye with the laser you get
green signal but once you follow through
then two hands are close to each other
and then the excitation by the later
becomes transferred to the red dye and
then you get red signal so by simply
looking at the color change you can
deduce a distance between the two hands
and they have the shape change of the
own of the protein during function so
this is like having a courtside seat
next to the Wimbledon center court and
observing what makes a federal
generational talent perhaps the best
ever now we are in Gangnam district so I
couldn’t resist the temptation to use
[Music]
whooping Gangnam style so as you can see
you can simply watch the color change
and deduce the dance moves of Si and you
can do this from far away you can do
this from the moon right by simply using
a powerful telescope to change the color
to see the color change in fact we can
now use these technologies to to see the
complicated and amazing dance movements
of many medically important proteins
such as oncogenes you know transmitter
transporters and an HIV before
transcriptase we have been doing doing
this for some years it still amazes me
every day while you can discover on a
of years back we are studying the
movement of DNA motor protein moving on
the DNA surprisingly instead of falling
off at the end of the DNA Street the
protein reappeared at the beginning of
the street and then repeated the
patrolling movements numerous times it
turns out the protein uses this
patrolling function to safeguard the
street from other proteins that can
potentially cause genomic damage because
extensive genomic damage can lead to
cancer and human development we now must
view these proteins as the superheroes
that keeps the threat of cancer at bay
that’s my heel okay in fact and if there
is a mutation in one of these human
resisting proteins that can lead to a
real problem for example just the six
letters change in a gene called breast
cancer susceptibility gene – also known
as bracha – if you have the mutation
then your chance of getting a breast
cancer
or ovarian cancer increases dramatically
famously the actress Angelina Jolie
surgically removed her organs because of
the broad commutations wouldn’t it be
amazing wonderful if instead we can
remove the disease causing mutations
from the genome altogether this dream
may become a reality soon because of the
technology called CRISPR and it may not
be to find the future when until we can
cut out a defective a portion of a gene
and replace it with a functional normal
copy in CRISPR technology for gene
editing there is a protein called test
nine that binds DNA and unwise a DNA to
examine the sequence if there’s a great
sequence match that CRISPR cast nine
custardy na to start genome editing
basically case nine protein is asking
the DNA are you my true partner before
making a commitment this technology
works wide enough to a triple the yield
of tomato plants without having to name
it at GMO
that’s because tomato genes can be
precisely edited without introducing a
gene from a different species you can
also use a crisp focus on technology to
cure mice of deafness causing mutations
and there are many amazing examples that
are highly promising however there are
still major problems a major one our
organs save medical applications yes 9
does not just cut at one place with a
perfect sequence match it can also cut
sequences that are partially matching
only this is called off-target effect
and because our genome is very large 3
build 3 billion letters of DNA they can
be of a large number of
harshly magical sequences that can be
cut by cast nine unintentionally and
causing you know unpredictable
consequences now we are using single
so if the cast nine binds the DNA to
unwind it fully when the sequence
matching is great basically you get a
green signal to tell the enzyme this is
good match you can settle down
marry her whatever right if there’s no
match then then you don’t unwind the DNA
you get your a signal so far so good
now for partially matching sequences
well ideally we want to have just red
line only okay but in reality when you
measured the activities we got a mixture
of red and green and this is a reason
why test nine protein actually are often
you know enters into a commitment of a
long-term relation even with less than
an ideal match using this understanding
that we are trying to engineer test nine
proteins that can be much more accurate
without us
side effects okay so proteins and nano
machines and superheroes and that’s the
message for today I want to invite
thanking you for being here we also want
to explain our research better and also
convey the excitement and the fun aspect
of the scientific enterprise to non
scientist and also to in a young student
so I commissioned a song about our
research from a Baltimore artist in the
Maryland us where I live and I’m going
the audience demon is here yeah
SM Fred please do not forget single
molecules and dyes the colors green and
red yeah SM pray you will not regret use
cast nine to cut like it’s Gillette with
Chris protect hey
in this lab we doing work with
fluorescence study as I’m kinetic
sequence the genus fnatic yeah
ATC inches we like to play with beams
cast nine on wise the genes and then it
cuts this is a jean skirt makes
evanescent fields shows us evanescent
fields shows us my fluorescence heals
you record the videos like we got out of
lesson feels getting attracted getting
repelled measuring habits what is this
pal molecular structure molecular
chatting and everything down Amelie
another wrapping optical trap yeah pull
on the strap straps yeah optical trap
yeah move on the map hey yeah you cannot
use fret with it the fluorophores
photobleach out of it get ready to laser
it you measure by moving the stage a bit
you look at its elements you pull and
you look at the range of it you pull and
you look at the strength of it you pull
and you start rearranging it time to
talk about single molecule imaging go
faster
naturally this imaging will come with
its limiting factors you focus on part
of the slides not that the others don’t
matter
super s will come select and I’ll choose
a variety
son Fred please do not forget don’t
single molecules and dyes the colors
better right yeah SM pray you will not
regret use guys night to cut like you
fill it with hay housing base pairs
without stop it splits your defense like
it scary when it’s walking here at TEDx
reven rep X cuz its new tech are fueling
case and Watson to flex we use friend
what spread the donors and acceptors you
split the channel like you splitting
into sectors the closer to dies the
higher the fret the further they go the
lower the red the green is the donor the
res acceptor reading the data like
reading the leash like reading the letters
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