[Music]
this is Streptococcus pyogenes a
pathogen that is responsible for a whole
host of human diseases from strep throat
to scarlet fever and necrotizing
fasciitis which is also known as the
flesh-eating disease
now despite its general nastiness this
is also a very fascinating bacteria when
you take a closer look at it you see
that it has these extremely long and
thin hair like appendages these are
called pili and they're important
virulence factors the bacteria use them
like hands to feel around and recognize
different surfaces recruit other
bacteria and initiate an infection these
hairs are made from a single repeating
protein unit that is linked together a
bit like links in a chain when you zoom
into the Tomic structure of a protein it
looks a bit like a string that's folded
into a ball this string is made from
building blocks called amino acids now
here's the interesting thing the
proteins that make their hair like
appendages on Streptococcus pyogenes and
other similar bacteria they contain a
very special chemistry that's not really
found in other places in nature these
proteins are not a linear string but
rather a circular string the ends of the
proteins are linked together by
spontaneously forming chemical bond
called an ISO peptide bond basically the
ends react with themselves to form a
very strong rock this makes the proteins
as strong as stones they become
indestructible you can boil them try to
cut them with enzymes or throw them in
strong acids and bases nothing happens
to them in fact these are some of the
strongest proteins that have ever been
discovered now the reason why I'm giving
you this quick primer about the specific
bacterium is that it was the subject of
my doctoral research at Oxford when
researching those strong chemical bonds
together with my advisor mark towers we
engineered these special proteins to
make a new kind of molecular super glue
think of it as a super cool they can buy
at the store you know the one that if
you stick your fingers together it's
impossible to unstick them our glue
creates this kind of a strong bond
except at the molecular level protein to
protein something like this it didn't
exist before it enables a variety of
applications such as engineering new
medicines developing vaccines making
biomaterials building tools at the
nanometer scale and much more so how do
you make goo from a stone strong protein
as I mentioned a protein is like a
string and these super-strong proteins
the ends are linked together by an ISO
peptide bond to make a circle to make a
groove I needed to break the circular
protein into two molecules that could
first specifically recognize each other
and no other proteins and then have the
ability to form a new chemical linked
with each other my working theory was
that if I split the proteins in such a
way as to separate the building blocks
that may be a super-tight bond then
those blocks would maintain the
capability of recognizing each other and
linking together even if they were
originally part of separate strings now
making things more difficult of course
was the fact that proteins have evolved
over many millions of years to form very
specific structures and they're really
like you only mess with those structures
if you try to change them they start
misbehaving and doing strange things so
after carefully studying the atomic
structure identified regions of the
string that would be least disruptive to
break and I start to break the protein
into two molecules and make a small
library of different versions then I
took the two parts and I simply mixed
them together
and indeed as I'd hoped for the two
components without any help we're able
to recognize each other in solution
refold into the original protein
structure
and glued together by forming a highly
specific and irreversible iso peptide
bond now from the slightly some versions
didn't work some worked a bit and some
work really well forming a very strong
bond one that once forms never comes
apart what I had was any kind of glue
that could be used to assemble proteins
and enzymes for instance so on that
basis I started to engineer the two
components try to find the best possible
versions and make it small and fast
screw that pretty much worked in any
situation I called the two components
spy tag and spy catcher so how did they
glue things together putting it simply
the split strings aren't just able to
recognize each other and only each other
but forming unique and special links
that allows them to fold together into a
ball but they're also able to lock again
and form an immovable bond and when they
lock they staple together
anything that's attached to them you can
program the two components into the
actual genes of any two proteins then
you make the proteins and as soon as the
good components to each other they
spontaneously react and form an
irreversible bond wanting the proteins
themselves together this happens in test
tubes on the outside of living cells and
inside living cells in other words
having engineered and formalize these
components allows us to build new
protein shapes as easy as playing with
LEGOs but and heroes always going to be
a but you're not just limited to
proteins you can chemically link the goo
components to other organic and
inorganic molecules like medicines DNA
metals are much more to build nanoscale
objects that can address important
scientific and medical needs and you can
also have a bit of fun along the way
it's kind of like playing nano scale
Lego so of course the enormous benefit
of having a protein glue that lets you
build new and interesting shapes is that
proteins are biology's workhorses
they're very diverse and are pretty much
responsible for everything the cell does
from the way the cells organized
it's shape how it interacts with the
outside wall and so on
that makes them fundamental to the
scientific and medical industries for
instance I mentioned earlier that a
circular bond makes a protein incredibly
strong so if you program the GU
components at the ends of an enzyme to
circularize it you can make that enzyme
resistant to boiling temperatures or
another example you can program proteins
to spontaneously assemble into a
three-dimensional scaffold they can
serve as a framework for holding cells
together for tissue engineering or you
can program bacteria to produce
biomaterials that contain the glue
components so that you can glue various
active parts to create materials that
not only exist or are able to actively
do things like a paint that contains
enzymes to produce new chemicals or if
you use a super glue for developing
vaccines instead of simply presenting
the immune system with a foreign
substance to initiate an immune response
you can break the foreign substance into
smaller parts and glue them onto a
scaffold kind of like decorating a
Christmas tree then by presenting the
decorated scaffold to the immune system
which becomes exposed so many different
parts of the foreign substance all at
the same time you can initiate a
stronger immune response and have a
potentially better vaccine or you can
rapidly assemble new antibody shapes in
many different ways
antibodies are an important part of the
body's natural defense system against
disease and they're also changing the
way we treat disease and having ways of
finding better antibodies can help us
make better medicines with this screw
antibodies can be broken into smaller
parts and reassemble the new
combinations to speed up the process of
finding new medicines now there's a
personal side to the story a decade ago
when I was starting my studies at Oxford
my intention was to develop a new
generation of antibodies for treating
cancer instead I ended up making glue
from the flesh-eating bacteria a glue
that makes building new bi structures as
easy as playing with LEGOs you might
imagine
shape they simply build it with proteins
I didn't get the chance to directly work
on developing a new generation of
antibodies for treating cancer as a
warrants when I first set out but I did
make a GU that many others have used
indirectly if we're trying to find new
antibodies for treating cancer and many
other innovations that could one day
help improve people's lives and I guess
that epitomizes science frustrating
amazing and filled with possibilities
all at the same time thank you
[Applause]