[Applause]
[Music]
I’m curious which is an advantage you
might
scientists however if you were to ask me
what kind of scientist I would actually
struggle to answer you that’s because
I’m an interfacial scientist one of a
growing number of academics who perform
their research at the interface of
disciplines in my instance my
backgrounds was in via chemistry but I
moved to a chemistry lab to do my PhD
research my next position was in a
physics lab where I studied structural
biology and now I’m a group leader at
the Leiden University Medical Center
were investigating the human immune
system this background was not driven by
any kind of plan academic or otherwise
instead I followed my curiosity this
does kind of mean that I don’t know
everything about anything but it also
means I know about varied fields of
research this background has left me
with an unusual mix of knowledge and
this allows me to build bridges between
fields of science and approach
scientific problems from unusual
unexpected directions this is a huge
advantage because science is one of the
most creative disciplines that one can
follow by its very nature sciences at
the forefront of human knowledge and
scientists are investigating things are
never before being investigated this
also obviously means thinking of things
that have never been thought of before
and this jump into the unknown requires
a burst of inspiration and creativity
being able to make connections between
seemingly disparate fields of research
therefore facilitates such a creative
approach I’m going to tell you today
about how work in my lab is are using
such a multidisciplinary approach to try
and understand how part of our immune
system is activated to do this I’ll be
borrowing ideas from immunology
synthetic biology chemistry and
microscopy this approach was recognized
as an innovative idea by the EU at last
year the European Research Council
awarded me one and a half million euros
[Applause]
thank you the human immune system
comprises two branches the innate and
the adaptive our innate immune system
comprises permanent things our body has
that try and quickly stop infection by
pathogens such as bacteria and viruses
this includes things like our skin and
stomach acid and we also have cells and
proteins that roll around inside us and
try and attack anything seen as foreign
or non-self in contrast our adaptive
immune system as the name suggests can
adapt and evolve over the period of our
lifetime to tackle new problems such an
infection by a brand new kind of virus
this is all mediated by antibodies and
is the basis of vaccination by far the
most important advancement in human
medicine bridging these two branches is
the complement system so named because
it complements the to complement
comprises around 30 proteins present in
our Bloods and tissues many of which
circulate in an inactive form complement
can be activated when antibodies binds
to the surfaces of cells and they form a
platform this platform acts like a
landing pad for the first protein of
complement which binds and then somehow
becomes activated and we want to
understand this process of activation
because complement proteins attack and
destroy targeted cells an understanding
this may lead to new ways of treating
infections and diseases such as cancer
which I’ll talk about later however at
the moment we don’t yet understands this
process of activation and one of the
reasons we don’t is because it is very
difficult to study individual proteins
proteins are the workhorses of our
bodies in us they perform almost all of
the mechanical structural and chemical
work of our bodies they’re made up of
sequential amino acids just like beads
on a string and it’s simply the order of
these amino acids which dictates the
structure and the function of each
protein for example one sequence of
amino acids will always fold to form
hemoglobin which carries oxygen around
our bodies and is the reason I
blood is red another sequence of amino
acids will always fold to form rhodopsin
which is found in our eyes and allows us
to see although there are only 20 common
amino acids predicting a protein
structure and function just from its
sequence of amino acids is incredibly
difficult this is one of the biggest
unsolved questions in biology and is
known as the protein folding problem
it’s actually something I worked on
during my PhD proteins fold reliably
into complex 3d shapes in a bottom-up
process called self-assembly and this is
different to the top-down processes
we’re all much more familiar with things
like sawing sanding and gluing the
chairs you’re sitting on or micro
fabricating the chips within your
smartphone these will require
manufacturing an outside influence
however all of you are here because of
self-assembly when you were conceived
your cells and their contents self
assembled and self organized on their
own to form human embryos that then grew
and divided again and again to form
adult humans no fabrication or
manufacturing step was ever required and
this is what proteins do all of the
information dictating a protein
structure and function is encoded within
the sequence of amino acids of the
protein itself this would be much like
taking all the components required to
build a computer just throwing them
together and then in the computer build
itself and it is this process of
self-assembly that is incredibly
difficult to understand and predicts
hence the protein folding problem so
what my lab is doing is bypassing this
big problem and instead using a material
that we do understand deoxyribonucleic
acid or DNA is the recipe book for our
bodies in us it contains all of the
information in the format of a genetic
code required to program a human body
but we can also use DNA as a nano scale
building material this is possible
because unlike proteins we do understand
how DNA self-assembles this is thanks to
work by physicists over the past couple
of decades who have uncovered many of
the rules governing how DNA folds
nowadays all we have to do is design the
shape we want mix together the correctly
strands and the desired construct will
spontaneously form we can make this DNA
cheaply in the lab only around the price
of a pack of aspirin we can also ensure
there contains no genetic code is
therefore biologically inert and safe is
just a building material the ability to
program strands of DNA to self-assemble
into complex 3d architectures is
essential because these kind of
molecules are far too small to be
manufactured using any kind of manual
process this tetrahedron in the corner
is only around 30 nanometers across
that’s about 5,000 times thinner than a
human hair to give you a sense of scale
if my thumb if the tetrahedron was a
size of my thumb then one of my hairs
would be about five times as wide as
this lecture theater and long enough to
reach the edge of space a hundred
kilometres up what we’re now doing is
making tiny DNA constructs that can bind
to proteins and guide them to adopt
specific shapes
we’re therefore reducing the protein
folding problem by using the DNA as a
kind of template or scaffold and the
reason we’re doing this is because we
already know that antibodies have to
form this platform to activate our
immune system and we also know that the
size and shape of this platform is
critical for immune system activation
with DNA we can easily change the size
and the shape of this antibody antibody
landing pad without having to understand
the much more complex folding rules of
the antibodies themselves we want to
look at exactly how this DNA is
affecting these antibodies and
activating our immune system however
proteins are very small and the protein
that activates the complement system is
only around 20 nanometers across that’s
even smaller than that DNA I was talking
about earlier to see such tiny molecules
we use a technique called electron
microscopy electron microscopes are very
similar in concept to the light
microscopes you’re all more familiar
with from school except they are very
large and very expensive this one cost
around 6 million euros but the reason we
use electrons is because we can give
them enough energy to
the actual atoms and individual protein
molecules themselves what you can see
here is a kind of cell shown in gray and
the complement system has literally
punched a hole in the top of it I was
able to take this information and
reconstruct the 3d shape of this pore to
understand how complement is killing
cells however giving electron so much
energy also means that they damage the
sample to limit this damage we cool
everything down to minus 180 degrees
Celsius which we do with liquid nitrogen
and this gives the technique its name
cryogenic electron microscopy or cryo am
the pioneers in the field of cryo-em won
the Nobel Prize in Chemistry last year
and we are fortunate enough to have in
Leiden two of the world’s most advanced
microscopes in the world that we’re
going to use to look at our DNA protein
complexes and the reason we’re doing all
of this is because we want to understand
how to activate our immune system
because when we understand it we can
exploit it I’ve already said that our
own immune system doesn’t attack our own
cells this is good we don’t want our
immune system attacking our bodies
however cancer is a disease of our own
cells tumors are caused when our cells
divide uncontrollably when and where
they shouldn’t
using these DNA templates or scaffolds
we’re hoping to target specific cancer
cell types to force our immune system to
destroy them in contrast to chemotherapy
all we have to do is add DNA and natural
substance and our immune system will
take care of the rest they should offer
a simple and cheap effective treatment
for cancer following my curiosity has
led me to come up with this research
idea and it’s led me to some exceptional
labs in both the UK and the Netherlands
we have met some really interesting
people and learn a lot about how
scientists from different disciplines
approach scientific problems and I’ve
learned that if you know everything
about something it means you’re at the
forefront of your field however if you
know a lot about a few things it means
you can create your own field so I would
say it doesn’t matter if you’re a
scientist or an artist to the politician
or an architect
we should all follow our curiosity we
should all learn as much as possible
about as many things as possible because
you never know what creative connections you’ll be able to make thank you
[Music]
I’m curious which is an advantage you
might
scientists however if you were to ask me
what kind of scientist I would actually
struggle to answer you that’s because
I’m an interfacial scientist one of a
growing number of academics who perform
their research at the interface of
disciplines in my instance my
backgrounds was in via chemistry but I
moved to a chemistry lab to do my PhD
research my next position was in a
physics lab where I studied structural
biology and now I’m a group leader at
the Leiden University Medical Center
were investigating the human immune
system this background was not driven by
any kind of plan academic or otherwise
instead I followed my curiosity this
does kind of mean that I don’t know
everything about anything but it also
means I know about varied fields of
research this background has left me
with an unusual mix of knowledge and
this allows me to build bridges between
fields of science and approach
scientific problems from unusual
unexpected directions this is a huge
advantage because science is one of the
most creative disciplines that one can
follow by its very nature sciences at
the forefront of human knowledge and
scientists are investigating things are
never before being investigated this
also obviously means thinking of things
that have never been thought of before
and this jump into the unknown requires
a burst of inspiration and creativity
being able to make connections between
seemingly disparate fields of research
therefore facilitates such a creative
approach I’m going to tell you today
about how work in my lab is are using
such a multidisciplinary approach to try
and understand how part of our immune
system is activated to do this I’ll be
borrowing ideas from immunology
synthetic biology chemistry and
microscopy this approach was recognized
as an innovative idea by the EU at last
year the European Research Council
awarded me one and a half million euros
[Applause]
thank you the human immune system
comprises two branches the innate and
the adaptive our innate immune system
comprises permanent things our body has
that try and quickly stop infection by
pathogens such as bacteria and viruses
this includes things like our skin and
stomach acid and we also have cells and
proteins that roll around inside us and
try and attack anything seen as foreign
or non-self in contrast our adaptive
immune system as the name suggests can
adapt and evolve over the period of our
lifetime to tackle new problems such an
infection by a brand new kind of virus
this is all mediated by antibodies and
is the basis of vaccination by far the
most important advancement in human
medicine bridging these two branches is
the complement system so named because
it complements the to complement
comprises around 30 proteins present in
our Bloods and tissues many of which
circulate in an inactive form complement
can be activated when antibodies binds
to the surfaces of cells and they form a
platform this platform acts like a
landing pad for the first protein of
complement which binds and then somehow
becomes activated and we want to
understand this process of activation
because complement proteins attack and
destroy targeted cells an understanding
this may lead to new ways of treating
infections and diseases such as cancer
which I’ll talk about later however at
the moment we don’t yet understands this
process of activation and one of the
reasons we don’t is because it is very
difficult to study individual proteins
proteins are the workhorses of our
bodies in us they perform almost all of
the mechanical structural and chemical
work of our bodies they’re made up of
sequential amino acids just like beads
on a string and it’s simply the order of
these amino acids which dictates the
structure and the function of each
protein for example one sequence of
amino acids will always fold to form
hemoglobin which carries oxygen around
our bodies and is the reason I
blood is red another sequence of amino
acids will always fold to form rhodopsin
which is found in our eyes and allows us
to see although there are only 20 common
amino acids predicting a protein
structure and function just from its
sequence of amino acids is incredibly
difficult this is one of the biggest
unsolved questions in biology and is
known as the protein folding problem
it’s actually something I worked on
during my PhD proteins fold reliably
into complex 3d shapes in a bottom-up
process called self-assembly and this is
different to the top-down processes
we’re all much more familiar with things
like sawing sanding and gluing the
chairs you’re sitting on or micro
fabricating the chips within your
smartphone these will require
manufacturing an outside influence
however all of you are here because of
self-assembly when you were conceived
your cells and their contents self
assembled and self organized on their
own to form human embryos that then grew
and divided again and again to form
adult humans no fabrication or
manufacturing step was ever required and
this is what proteins do all of the
information dictating a protein
structure and function is encoded within
the sequence of amino acids of the
protein itself this would be much like
taking all the components required to
build a computer just throwing them
together and then in the computer build
itself and it is this process of
self-assembly that is incredibly
difficult to understand and predicts
hence the protein folding problem so
what my lab is doing is bypassing this
big problem and instead using a material
that we do understand deoxyribonucleic
acid or DNA is the recipe book for our
bodies in us it contains all of the
information in the format of a genetic
code required to program a human body
but we can also use DNA as a nano scale
building material this is possible
because unlike proteins we do understand
how DNA self-assembles this is thanks to
work by physicists over the past couple
of decades who have uncovered many of
the rules governing how DNA folds
nowadays all we have to do is design the
shape we want mix together the correctly
strands and the desired construct will
spontaneously form we can make this DNA
cheaply in the lab only around the price
of a pack of aspirin we can also ensure
there contains no genetic code is
therefore biologically inert and safe is
just a building material the ability to
program strands of DNA to self-assemble
into complex 3d architectures is
essential because these kind of
molecules are far too small to be
manufactured using any kind of manual
process this tetrahedron in the corner
is only around 30 nanometers across
that’s about 5,000 times thinner than a
human hair to give you a sense of scale
if my thumb if the tetrahedron was a
size of my thumb then one of my hairs
would be about five times as wide as
this lecture theater and long enough to
reach the edge of space a hundred
kilometres up what we’re now doing is
making tiny DNA constructs that can bind
to proteins and guide them to adopt
specific shapes
we’re therefore reducing the protein
folding problem by using the DNA as a
kind of template or scaffold and the
reason we’re doing this is because we
already know that antibodies have to
form this platform to activate our
immune system and we also know that the
size and shape of this platform is
critical for immune system activation
with DNA we can easily change the size
and the shape of this antibody antibody
landing pad without having to understand
the much more complex folding rules of
the antibodies themselves we want to
look at exactly how this DNA is
affecting these antibodies and
activating our immune system however
proteins are very small and the protein
that activates the complement system is
only around 20 nanometers across that’s
even smaller than that DNA I was talking
about earlier to see such tiny molecules
we use a technique called electron
microscopy electron microscopes are very
similar in concept to the light
microscopes you’re all more familiar
with from school except they are very
large and very expensive this one cost
around 6 million euros but the reason we
use electrons is because we can give
them enough energy to
the actual atoms and individual protein
molecules themselves what you can see
here is a kind of cell shown in gray and
the complement system has literally
punched a hole in the top of it I was
able to take this information and
reconstruct the 3d shape of this pore to
understand how complement is killing
cells however giving electron so much
energy also means that they damage the
sample to limit this damage we cool
everything down to minus 180 degrees
Celsius which we do with liquid nitrogen
and this gives the technique its name
cryogenic electron microscopy or cryo am
the pioneers in the field of cryo-em won
the Nobel Prize in Chemistry last year
and we are fortunate enough to have in
Leiden two of the world’s most advanced
microscopes in the world that we’re
going to use to look at our DNA protein
complexes and the reason we’re doing all
of this is because we want to understand
how to activate our immune system
because when we understand it we can
exploit it I’ve already said that our
own immune system doesn’t attack our own
cells this is good we don’t want our
immune system attacking our bodies
however cancer is a disease of our own
cells tumors are caused when our cells
divide uncontrollably when and where
they shouldn’t
using these DNA templates or scaffolds
we’re hoping to target specific cancer
cell types to force our immune system to
destroy them in contrast to chemotherapy
all we have to do is add DNA and natural
substance and our immune system will
take care of the rest they should offer
a simple and cheap effective treatment
for cancer following my curiosity has
led me to come up with this research
idea and it’s led me to some exceptional
labs in both the UK and the Netherlands
we have met some really interesting
people and learn a lot about how
scientists from different disciplines
approach scientific problems and I’ve
learned that if you know everything
about something it means you’re at the
forefront of your field however if you
know a lot about a few things it means
you can create your own field so I would
say it doesn’t matter if you’re a
scientist or an artist to the politician
or an architect
we should all follow our curiosity we
should all learn as much as possible
about as many things as possible because
you never know what creative connections you’ll be able to make thank you
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