Water is fundamental to all life.
Digestion, brain chemistry, drug metabolism...
Almost all biology, even if you can't see it, has to take place in water.
It's the most important liquid of life.
So most of the time when people think about water they think about it as this magical
substance where biology happens.
It isn't until quite recently that we really paid attention to what water is doing in biology
on the atomic scale where everything is actually happening.
Hi, my name is Sylvia, I run a research group at the University of Oxford in the Dept of
Biochemistry,
where we're trying to understand how water interacts with the processes of life.
What we're looking at is the structure of molecules in solution.
Biomolecules, things like proteins or DNA, but importantly we're looking at thow the
structure of molecules are hydrated by water in solution.
The difficulty with understanding water, especially in solution and at the atomic scale, is it's
difficult to measure by most techniques.
In many techniques the water itself is invisible.
If you take a protein as an example, pretty much every organism has proteins.
They're the 'working horses' in our bodies.
DNA code gives the blueprint to make protein.
Proteins are made from very long chains of building blocks which we call amino acids,
which fold up into these complex three-dimensional structures in order to function.
All of this for the most part takes place in solution.
More interestingly, it has to fold in exactly the right way or it won't work.
And I mean exactly.
Somehow, your proteins in your body, in solution, fold into the same structure over and over
and over and over again.
But nobody really knows why.
If you can understand the mechanisms that control the way proteins fold,
you would have a very good way of trying to prevent different forms of disease.
My name is Alan, I'm an instrument scientist.
I do neutron scattering experiments on a whole variety of liquids and disordered material.
Cancer, Alzheimer's, dementia, any of these diseases are almost invariably something to
do with proteins not folding the way they're suppose to.
So there's been a huge debate going on about what interactions with the water cause these
proteins to fold the way they do.
The current theory as to what water is doing in this process is that water is basically
passive,
that's it's just a medium where proteins fold up.
Traditionally the idea has been that the water forms like a shell,
around groups in the protein molecular that are called hydrophobic:
they are 'water fearing'.
They dont' like water being around them.
Water doesn't like to form bonds with them.
The idea was that it was these hydrophobic groups that were pushing the protein into
the structure it had.
Most of this theory is based on computation, which is a good thing,
but it needs to be experimentally verified.
So some of the work that we've been doing is showing that water's playing a more active
role than previously had been thuoght.
We think that it's actually doing things like providing a helping hand and allowing proteins
to start that folding process.
We're using a technique that's more commonly used in physics to look at the structure of
water around biological molecules in solution.
To do this, we go to the ISIS Neutron and Muon Spallation Source in order to do our
experiments.
Well, ISIS is a neutron source, obviously.
Accelerates particles of protons, hit heavy metal targets, which produce a neutron pulse
by a process called spallation.
We have a linear accelerator, and then a synchotron, which groups the protons together into packets,
then we run them down and hit them into a target, and once they hit the target they
spallate, and the neutrons then come off really fast so we have to cool them down, it's a
process called moderation.
Then after moderation we guide them in a collimator down to be incident on our sample.
We're firing neutrons at our sample, which is in solution, so it's in the liquid state,
and they bounce off your nuclei and interact with each other when they bounce off and create
a pattern which we can use to understand the three-dimensional structure of what's happening
in our solution.
If you think about a molecule that's moving, you're going to take individual snapshots
here, here, here, here and here...
So in a way we can trap different bits of our protein in teh process of folding.
But at each stage we can see what the water's doing because we're building up a comlpex
snapshot of everythings that's happening.
Then you can put it all together in a picture of how water is hydrating the molecules, how
different the sizes of the chains are, how far apart they are.
Importantly we're measuring on the atomistic scale, so you see the atoms and how close
the water atoms get to each other.
I think the overarching theme that keeps emerging to us is that water really is being active.
It's not just being passively excluded from a protein interior adn then going about its
business,
it's actually doing something.
It has to be there,
and it has to be there to drive this process.
So the water is acting as an intermediary between the hydrogen bond sites on different
parts of the protein and pulling them together.
That seems to be the picture we're getting out of this.
We don't see evidence for this so-called hydrophobic interaction.
If we're right about water-mediated processes and water has a quite integral role to biology,
then this has significant implications.
It has implications for disease control, it has implications for designing better drugs,
that hydrate in the right way so that they can map for instance the way hydration is
in the place in a protein where the drug has to bind to in order to have its function.
But we may not be right either.
This is the way theories develop in science.
You take a set of evidence, and then you come up with your best theory of that evidence
and it works great until you get another piece of evidence,
and then it all falls apart, and so you have to restructure your theory or modify it or
just be proven wrong.
I think as a scientist you're not really doing your job if you're not proven wrong at least
once or twice in your career.
We're working at the edge of stuff and just starting to get new data so it's not something
that's old.
We're pushing the boundaries of our techniques and the way we think about things,
and that's the fun part.