dressing for the occasion yes yes I've
put on my famous chemists tie most of
them all quite a few Nobel Prize winners
though a few predate them just about to
do the video about the Nobel Prize I
need somebody to sit in Diane's office
yes it will come this year's prize deals
with cells and Sensibility
the Royal Swedish Academy of Sciences
it's really more for biochemistry and
molecular biology and I don't know
either of the people but it sounds quite
interesting
this year's prize is for something that
I know nothing about though I can
understand White's importance yes sir my
name's Barry Callum I'm an associate
professor of medicinal pharmaceutical
chemistry here in the School of Pharmacy
at the University of Nottingham
unfortunately when Nobel created the
prize he didn't have anything that
covered what is now called molecular
biology I was really hoping that these
guys would actually get this because
this is this is a reflection of decades
of quality research and so it's right
that some of the chemistry prizes should
be for that when you when you look at
g-protein couple receptors these these
are basically one of the key receptors
that are expressed in in almost all of
your cells throughout the body and they
are effectively acting like the lock
that a key fits in to open up activity
that needs to resign or occur within the
cell for your body to function so your
body is full of cells like this and
circulating through the body are
hormones which are released for example
when you're frightened and I get booed
so one of them most well-known is
adrenaline adrenaline is a key
neurotransmitter in indeed the work of
one of the Nobel Prize recipients Bob
Lefkowitz
he's his major sort of efforts where he
was the first person to actually clone
the receptor or the beat Regina scepter
the adrenaline acts at within the body
and the key point is that the hormones
which are quite small molecules can't go
through the outer layer of the cell the
membrane but instead there are so-called
receptors the subject of this prize
g-protein coupled receptors which sit in
the outer surface of the of the membrane
and go through it so when the molecule
arrives on this side it sends a message
into the cell so these receptors are are
the middleman they are the gatekeeper
that basically translate the message
that that neurotransmitter needs to
deliver to the inside of the cell to
exert its effect in the Nobel Prize
announcement the professor who was
talking about this was quite lucky
had seven rods because the structure of
the molecule involves seven strands
which she had quite nice long rods I've
only got pens so you can see seven of
them then it'll bundle so this is the
outside and this is the inside of the
cell so when the adrenaline goes into
here it pushes the bundles apart because
the chains are rigid like my pen then
what happens at this end effects that
end and the clever thing is depending on
which molecule docks on the outside so
the insides of the rods are pushed down
different amounts inside the cell there
are different proteins swimming around
and if it split pushed out a small
amount this one can go in but if it's
pushed out a much bigger amount then
this one can go in so this is a computer
image of one of the first crystal
structures that came out of Quebecers
lab this is the human beta to audrina
scepter the one that I mentioned that is
in the the tubes of your lungs and it
resides in the membrane through these
these sort of helical units that's where
it binds in the membrane so you have the
cell membrane here and then the ligand
comes in from the top and you can just
see in there that the ligand is bound I
can sort of just quickly sort of so the
ligand is is just bound in here so
that's that's about sort of a third of
the way down and when it binds in it
causes the receptor to change shape and
that information is relayed down to the
part that is in the pointing to the
inside of the cell they are there
beautiful structures they've got the
from called the serpentine receptors
because they weave in and out of the
cell membrane with these seven
transmembrane regions so it looks like
it sometimes we knew you have seen them
in a cartoon in a book that you're like
a snake weaving in and out now the
reason why this is also important is
that about 50% of the drugs that you
annotate the pharmaceutical products
operate have their effect by interacting
with these
scepters and they're not quite the same
shape as adrenaline or dopamine or other
hormones but they're sufficiently
similar that they will affect just some
of the receptors so you can get very
selective behavior and treat a pacific
condition have you ever met these guys I
have met both of them and in fact I'm
talking at a conference in Melbourne
this Christmas just before Christmas on
on g-protein couple receptors and
Lefkowitz and kobilka are topping and
tailing the program with the two
keynotes so I'll get to meet them again
yeah absolutely
now what did actually the two Nobel
Prize winners do the Nobel Prize gets
awarded in December these guys might not
get to your conference I think they
should do
I can't member the date of the Nobel
Prize ceremony is the conference's first
week in December in Melbourne at Monash
University what they did was to work out
this structure by very careful
experimentation isolating these
receptors from the cells and then using
x-ray crystallography to work out the
structure almost in atomic detail so it
sounds to me like these guys have given
you the ultimate blueprint of the
keyhole so all you guys around the world
can now make all the keys absolutely and
from this early work there are now quite
a number of papers that have come out
that have reported other g-protein
couple receptors crystal structures
which is extraordinary that we can now
understand how these receptors work
which are just a small part of each cell
two level of almost the individual atoms
and of course once you know the
structures then you can start designing
even more specific and better drugs so
there are millions and millions of
people worldwide that suffer with asthma
it's a debilitating disease where that
particular disease manifests itself in
their inability to breathe easily
they have constriction of the the tubes
in their lungs and they find it very
difficult to breathe one of the drugs
is used to combat that is a agonist
molecule a molecule stimulates one of
these g-protein coupled receptors this
is the beta audrina scepter that resides
within the bronchioles or the tubes of
the lungs and what you'll notice that
often a patient that has asthma if
they're having an asthma attack will
pull out their classic blue inhaler and
take a puff and that puff delivers a
effectively a molecule that mimics
adrenalin binds to the beecher adrene
acceptors in the lungs and the effect of
that ligand binding to the betrayed
receptor in the lungs is to open the
lungs relax the tube so they open up so
the air can pass more easily into the
lungs and the patient can breathe again
that's just one particular disease state
there are a whole myriad of diseases
where g-protein coupled receptor
modulation by drugs allows people to
live normal lives I think it's a really
well deserved prize and I don't think
anybody could grab such a wonderful
piece of work being rewarded with this
prize
in my pocket I've got this and this is a
real Nobel Prize medal