[Music]
my father was a translator he spoke five
languages fluently and he was pretty
good at lots of others as well I used to
marvel when I was a child we go on
holiday to different countries he could
converse with different people
whatever the land we were in they could
understand him he could understand them
sadly I didn’t inherit his linguistic
skills but methods of communication have
remained with me as a fascination
throughout my life
what about messages what do they convey
how do we decipher them how do we act on
the information that we get can this
translate not just into humans but into
other things other forms of life I was
always interested in science and in
particular the science of the human body
and how the body responds to threats
from the environment how do we protect
ourselves from infection what are the
cells that are used in protecting the
body from infection the cells of the
immune system
so I was lucky enough to become an
immunologist and now I spend my time
studying those cells studying how they
respond to infectious threats and other
threats in the environment and what I’ve
learnt is a key component of how the
immune system responds is the
communication between the cells the
cells are speaking to each other and
that’s how we manifest our defense of
the body let’s think about the lungs
I’ve become very interested in the
immune system in the lungs now I hope
you’re all still breathing yeah we
haven’t lost anybody yet that’s good
every time you breathe you’re breathing
in and out about a half a liter of air
that equates to about 10,000 liters of
air that pass through our lungs every
day
everything in the air
we’re breathing and let’s think about
the challenges that poses to the lungs
and in particular I want to tell you
about a group of cells called epithelial
cells these are cells that form the
barrier in the lungs between the body
the lungs themselves and the external
environment the air that we are
breathing and if you think about it they
have a very very challenging job to do
because yes we want to keep out noxious
particles viruses and bacteria so they
have to be able to do that but also they
have to allow us to exchange the gases
that we need for life every time we
breathe in we’re taking a little little
oxygen from the air we breathe and we’re
returning a bit of carbon dioxide so
these barrier cells are actually very
useful to us these epithelial cells that
act as barriers there allow us to
exchange gases and they must protect us
they must keep the outside out and the
inside in and for a long time that’s all
we thought they did we just thought they
were barriers that they didn’t have much
other functioning now we know of course
that they do and in fact a key part of
how they protect us from the outside
environment how they maintain the
integrity of the lungs how they keep us
free from infection is that they
communicate with other cells and some of
the important cells that they
communicate with are called macrophages
that literally means cells that go
around eating things they’re big eaters
and the epithelial cells tell the
macrophages what’s in the environment
they send signals they communicate with
the environment they send signals to the
macrophages so that if there’s an
infection coming if there’s a bacteria
they’ve encountered for exam
the macrophages become activated to deal
with that threat and we call these
activated macrophages M 1 as
immunologists we’re not very imaginative
so these are M 1 and they’re very
aggressive they’re spoiling for a fight
they’ll kick the hell out of bacteria
but of course they might damage the
surrounding just like in a bar brawl
lots of windows get smashed so they take
out the invaders but they can cause
damage so we have to limit their
aggression and so the barrier cells also
have to send signals to macrophages to
calm them down and in their calm state
they’re chilled out state they’re known
as m2 again very imaginative
so the m2 macrophages are laid-back and
what they do is they stop the m1
macrophages from being aggressive and
the m2 macrophages go in and they repair
any damages done they repair that
barrier those epithelial cells clearly
the signaling between the epithelial
cells and the macrophages is very
important and sometimes the macrophages
return the favor they signal back to the
epithelial cells as we shall see a bit
later on they can instruct the
epithelial cells to do things but this
communication between the cells
regulates the activity and it keeps us
healthy it keeps our lungs healthy as we
breathe we breathe in everything in the
air particles of soot bacteria people
coughing viruses diesel particles
organic matter everything in the air
that we are breathing passes into our
lungs and of course that can cause
damage to the lungs if we know how the
damage is caused and perhaps which
pollutants are causing that damage then
maybe we can do something about it and
the World Health Organization tell us
that in the past year over 7 million
people have died from air
that’s about one in eight of the total
deaths in the world is due to breathing
polluted and contaminated air and that’s
a problem
in our country and particularly in many
of the developing countries around the
world pollutants can corrupt the
signaling between those cells pollutants
very often can activate the em1 those
aggressive macrophages and keep them
switched on so we get lots of damage as
a result of course we can get chronic
diseases asthma COPD chronic obstructive
pulmonary disease and many others that
caused the deaths that we see due to air
pollution other pollutants can activate
the m-2 macrophages and keep them
switched on and what can happen then is
we get aberrant thickening of the
epithelial cells and we might leave
ourselves open to infection from
bacteria and from viruses if we can
understand those signals if we can
understand the language between the
epithelial cells and the macrophages and
how the pollutants can corrupt that
language then maybe we can start to do
something about it
and that’s the task that I set myself
and my research group now the first
thing to do of course is to find some
lungs we want to work on this signaling
between epithelial cells barrier cells
in the lungs and immune cells the
macrophages that interact with them so
I’d like volunteer to donate some of
their lungs it’s all in a good cause in
science yeah I usually get that response
not too many people want to give me some
of their lungs actually there are some
people that do and there’s a technique
called bronchoalveolar lavage where you
put a salt solution into the lungs and
you wash out the lungs and with that
comes some cells and we can grow the
cells but we don’t really want to do
that it’s a bit of an inconvenience and
I wouldn’t recommend that you volunteer
for that
frankly what we’ve done is developed
cells that grow continuously but are
actually very very much like the
alveolar epithelial cells and
macrophages the cells of the lung that
we want to study we can grow these soul
cells together in special chambers in
the lab so they’re like a lab lung so
now we have a system that we can
interrogate we can put different
pollutants into that system and that’s
what we’re doing we can add extracts
from diesel exhaust particles we can add
allergens we can add organic matter
that’s come from composting or intensive
agriculture sites that’s exactly what
we’re doing and we’re looking at the
responses that the macrophages have are
they aggressive are they chilled out
are they m1 are they m2 what’s happening
to the epithelial cells we can study all
these things in this lab lung that we’ve
got now the cells don’t talk to each
other using words would be great if they
did but they talk to each other by
producing small proteins those proteins
are called cytokines so if we can
identify those proteins that would be
like identifying the language and then
we could translate what they were saying
we could understand the language of the
cells so that’s what we need to do and
that’s what we’ve been doing we’ve been
taking samples from our lab lung our
cell cultures that have had different
stimulants added to them different
pollutants and we’ve taken the mixture
containing all the proteins that these
cells are communicating to each other
with and we we’re trying to identify
what they are sometimes the macrophages
talk back to the epithelial cells and if
there are particular stresses in the
environment the macrophages instruct the
epithelial cells to commit suicide it’s
a process called apoptosis
now sometimes this can be actually
beneficial but of course many times it
can be detrimental and if you look at
the difference between the the pictures
the micrographs that you can see on the
slides you can see that on the left
you’ve got a nice mixture of macrophages
and epithelial cells but the main
difference is on the right that many of
those cells have disappeared those are
the epithelial cells that have committed
suicide under instruction from the
macrophages so we’re interested in what
those signals are as well what’s that
language okay to understand a language
we need a translator just much like when
we started I told you about my father
translating languages we have to have a
translator that can understand the
protein language that the cells are
speaking to each other
we have to be able to take all the
proteins in our system put it through a
translator and hopefully some sensible
sentences might come out the other end
and to do that we use sophisticated
equipment called a mass spectrometer
what this does is it smashes up all the
proteins into tiny fragments and then it
separates those fragments according to
their mass and it turns out that the
mass of the fragments are unique to
different proteins so if we can identify
the fragments from their masses we can
work back and tell which proteins are
present and that’s exactly what we’re
doing we’re looking at all the proteins
in our system something called
proteomics we’re analyzing that and then
deciphering what proteins are produced
under different conditions what
pollutants are inducing certain proteins
and what’s the response from our
macrophages so this is the language of
the cells this is the protein language
of the cells it turns out the protein
language is quite complex but we’re
starting to understand it we’ve got a
rudimentary understanding of the
language of the cells and this will
allow us to make predictions about how
the cells might respond in different
situations
so what if we found out we’ve been able
to grow lung cells in the lab we’ve been
able to add different stimulants
different pollutants to these lung cells
and we’ve been able to look at whether
they induce the aggressive m1
macrophages or the chilled-out m2
macrophages and how that impacts on the
barrier cells we’ve been able to find
out some of the protein language that
instructs the aggressive m1 macrophage
or the chilled-out m2 macrophage and
this is allowing us to develop drugs
that can maybe change that language so
that when we’re faced with pollutants or
other stresses that switch on the
aggressive m1 we can change that
language we can modify it back to a
language it tells them to to chill out
of it so we might be able to treat or
even prevent diseases such as asthma and
other airway diseases the more we
understand about this language this
protein language of the cells and more
than that our mini lung is also we can
work the ank language back the other way
we can look at what it’s telling us and
then understand what’s in the
environment around us what is in the air
around us so we’re using our cells as
sensors to tell us what’s around every
breath we take
so please think about the language of
the cells with every breath you take
thank you
[Applause]
my father was a translator he spoke five
languages fluently and he was pretty
good at lots of others as well I used to
marvel when I was a child we go on
holiday to different countries he could
converse with different people
whatever the land we were in they could
understand him he could understand them
sadly I didn’t inherit his linguistic
skills but methods of communication have
remained with me as a fascination
throughout my life
what about messages what do they convey
how do we decipher them how do we act on
the information that we get can this
translate not just into humans but into
other things other forms of life I was
always interested in science and in
particular the science of the human body
and how the body responds to threats
from the environment how do we protect
ourselves from infection what are the
cells that are used in protecting the
body from infection the cells of the
immune system
so I was lucky enough to become an
immunologist and now I spend my time
studying those cells studying how they
respond to infectious threats and other
threats in the environment and what I’ve
learnt is a key component of how the
immune system responds is the
communication between the cells the
cells are speaking to each other and
that’s how we manifest our defense of
the body let’s think about the lungs
I’ve become very interested in the
immune system in the lungs now I hope
you’re all still breathing yeah we
haven’t lost anybody yet that’s good
every time you breathe you’re breathing
in and out about a half a liter of air
that equates to about 10,000 liters of
air that pass through our lungs every
day
everything in the air
we’re breathing and let’s think about
the challenges that poses to the lungs
and in particular I want to tell you
about a group of cells called epithelial
cells these are cells that form the
barrier in the lungs between the body
the lungs themselves and the external
environment the air that we are
breathing and if you think about it they
have a very very challenging job to do
because yes we want to keep out noxious
particles viruses and bacteria so they
have to be able to do that but also they
have to allow us to exchange the gases
that we need for life every time we
breathe in we’re taking a little little
oxygen from the air we breathe and we’re
returning a bit of carbon dioxide so
these barrier cells are actually very
useful to us these epithelial cells that
act as barriers there allow us to
exchange gases and they must protect us
they must keep the outside out and the
inside in and for a long time that’s all
we thought they did we just thought they
were barriers that they didn’t have much
other functioning now we know of course
that they do and in fact a key part of
how they protect us from the outside
environment how they maintain the
integrity of the lungs how they keep us
free from infection is that they
communicate with other cells and some of
the important cells that they
communicate with are called macrophages
that literally means cells that go
around eating things they’re big eaters
and the epithelial cells tell the
macrophages what’s in the environment
they send signals they communicate with
the environment they send signals to the
macrophages so that if there’s an
infection coming if there’s a bacteria
they’ve encountered for exam
the macrophages become activated to deal
with that threat and we call these
activated macrophages M 1 as
immunologists we’re not very imaginative
so these are M 1 and they’re very
aggressive they’re spoiling for a fight
they’ll kick the hell out of bacteria
but of course they might damage the
surrounding just like in a bar brawl
lots of windows get smashed so they take
out the invaders but they can cause
damage so we have to limit their
aggression and so the barrier cells also
have to send signals to macrophages to
calm them down and in their calm state
they’re chilled out state they’re known
as m2 again very imaginative
so the m2 macrophages are laid-back and
what they do is they stop the m1
macrophages from being aggressive and
the m2 macrophages go in and they repair
any damages done they repair that
barrier those epithelial cells clearly
the signaling between the epithelial
cells and the macrophages is very
important and sometimes the macrophages
return the favor they signal back to the
epithelial cells as we shall see a bit
later on they can instruct the
epithelial cells to do things but this
communication between the cells
regulates the activity and it keeps us
healthy it keeps our lungs healthy as we
breathe we breathe in everything in the
air particles of soot bacteria people
coughing viruses diesel particles
organic matter everything in the air
that we are breathing passes into our
lungs and of course that can cause
damage to the lungs if we know how the
damage is caused and perhaps which
pollutants are causing that damage then
maybe we can do something about it and
the World Health Organization tell us
that in the past year over 7 million
people have died from air
that’s about one in eight of the total
deaths in the world is due to breathing
polluted and contaminated air and that’s
a problem
in our country and particularly in many
of the developing countries around the
world pollutants can corrupt the
signaling between those cells pollutants
very often can activate the em1 those
aggressive macrophages and keep them
switched on so we get lots of damage as
a result of course we can get chronic
diseases asthma COPD chronic obstructive
pulmonary disease and many others that
caused the deaths that we see due to air
pollution other pollutants can activate
the m-2 macrophages and keep them
switched on and what can happen then is
we get aberrant thickening of the
epithelial cells and we might leave
ourselves open to infection from
bacteria and from viruses if we can
understand those signals if we can
understand the language between the
epithelial cells and the macrophages and
how the pollutants can corrupt that
language then maybe we can start to do
something about it
and that’s the task that I set myself
and my research group now the first
thing to do of course is to find some
lungs we want to work on this signaling
between epithelial cells barrier cells
in the lungs and immune cells the
macrophages that interact with them so
I’d like volunteer to donate some of
their lungs it’s all in a good cause in
science yeah I usually get that response
not too many people want to give me some
of their lungs actually there are some
people that do and there’s a technique
called bronchoalveolar lavage where you
put a salt solution into the lungs and
you wash out the lungs and with that
comes some cells and we can grow the
cells but we don’t really want to do
that it’s a bit of an inconvenience and
I wouldn’t recommend that you volunteer
for that
frankly what we’ve done is developed
cells that grow continuously but are
actually very very much like the
alveolar epithelial cells and
macrophages the cells of the lung that
we want to study we can grow these soul
cells together in special chambers in
the lab so they’re like a lab lung so
now we have a system that we can
interrogate we can put different
pollutants into that system and that’s
what we’re doing we can add extracts
from diesel exhaust particles we can add
allergens we can add organic matter
that’s come from composting or intensive
agriculture sites that’s exactly what
we’re doing and we’re looking at the
responses that the macrophages have are
they aggressive are they chilled out
are they m1 are they m2 what’s happening
to the epithelial cells we can study all
these things in this lab lung that we’ve
got now the cells don’t talk to each
other using words would be great if they
did but they talk to each other by
producing small proteins those proteins
are called cytokines so if we can
identify those proteins that would be
like identifying the language and then
we could translate what they were saying
we could understand the language of the
cells so that’s what we need to do and
that’s what we’ve been doing we’ve been
taking samples from our lab lung our
cell cultures that have had different
stimulants added to them different
pollutants and we’ve taken the mixture
containing all the proteins that these
cells are communicating to each other
with and we we’re trying to identify
what they are sometimes the macrophages
talk back to the epithelial cells and if
there are particular stresses in the
environment the macrophages instruct the
epithelial cells to commit suicide it’s
a process called apoptosis
now sometimes this can be actually
beneficial but of course many times it
can be detrimental and if you look at
the difference between the the pictures
the micrographs that you can see on the
slides you can see that on the left
you’ve got a nice mixture of macrophages
and epithelial cells but the main
difference is on the right that many of
those cells have disappeared those are
the epithelial cells that have committed
suicide under instruction from the
macrophages so we’re interested in what
those signals are as well what’s that
language okay to understand a language
we need a translator just much like when
we started I told you about my father
translating languages we have to have a
translator that can understand the
protein language that the cells are
speaking to each other
we have to be able to take all the
proteins in our system put it through a
translator and hopefully some sensible
sentences might come out the other end
and to do that we use sophisticated
equipment called a mass spectrometer
what this does is it smashes up all the
proteins into tiny fragments and then it
separates those fragments according to
their mass and it turns out that the
mass of the fragments are unique to
different proteins so if we can identify
the fragments from their masses we can
work back and tell which proteins are
present and that’s exactly what we’re
doing we’re looking at all the proteins
in our system something called
proteomics we’re analyzing that and then
deciphering what proteins are produced
under different conditions what
pollutants are inducing certain proteins
and what’s the response from our
macrophages so this is the language of
the cells this is the protein language
of the cells it turns out the protein
language is quite complex but we’re
starting to understand it we’ve got a
rudimentary understanding of the
language of the cells and this will
allow us to make predictions about how
the cells might respond in different
situations
so what if we found out we’ve been able
to grow lung cells in the lab we’ve been
able to add different stimulants
different pollutants to these lung cells
and we’ve been able to look at whether
they induce the aggressive m1
macrophages or the chilled-out m2
macrophages and how that impacts on the
barrier cells we’ve been able to find
out some of the protein language that
instructs the aggressive m1 macrophage
or the chilled-out m2 macrophage and
this is allowing us to develop drugs
that can maybe change that language so
that when we’re faced with pollutants or
other stresses that switch on the
aggressive m1 we can change that
language we can modify it back to a
language it tells them to to chill out
of it so we might be able to treat or
even prevent diseases such as asthma and
other airway diseases the more we
understand about this language this
protein language of the cells and more
than that our mini lung is also we can
work the ank language back the other way
we can look at what it’s telling us and
then understand what’s in the
environment around us what is in the air
around us so we’re using our cells as
sensors to tell us what’s around every
breath we take
so please think about the language of
the cells with every breath you take
thank you
[Applause]
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