So close I can taste it!
Favourite Thing: Shooting Crystals.
Newcastle-Under-Lyme School – GCSEs (1994) A-levels (1996) BSc in Biochemistry from the University of Birmingham in 2000.
MRes in Structural Biology, PhD in Protein Crystallography
2 and a half years at Cancer Research UK in London, 7 years at the University of Manchester
Post Doc at the University of Manchester
The University of Manchester, funded by Arthritis Research UK.
Me and my work
I’m trying to figure out how and why we get Arthritis.
I am interested in a protein found in our blood called “Inter-alpha-Inhibitor” (I-alpha-I for short). When we get Arthritis (or other joint injuries and diseases) this protein gets into our joints. At the moment, we don’t know if this is a good thing or a bad thing.
It might be trying to repair our joints, or it might be making them worse!
We are looking at the 3D structure of this protein, and how this protein affects cells in the joint to try and figure out what it is doing, whether it is “friend or foe”.
If it turns out it is a friend – then that’s great – we could perhaps inject more of it into the joint to speed up the repair process.
If it turns out to be a foe, we can try and find ways of stopping it getting into the joint, or stopping it doing harm once it is there.
In the end, we want to try and help people with arthritis get better, faster.
My Typical Day
Grow cells, kill cells, extract protein, crystallise protein, shoot crystals, repeat.
I’m a crystallographer and a biophysicist, so I tend to spend a lot more time in front of a computer than most biologists. I also drink an obscene amount of coffee to try and keep me going through the day!
I spend quite a lot of time making my own reagents to conduct experiments – these are normally proteins or bits of proteins that we are interested in studying.
Having made the proteins, I can then go and test their activity on all sorts of equipment – I am mostly interested in which other proteins my proteins stick(bind) to – when proteins bind to one another there is often a functional result that might be important for the disease I am studying – so it is really important that I understand this for my protein.
I am also a crystallographer, which means that I use crystallography to understand the precise structure of my protein, down to where the individual atoms within the protein sit. In order to do this, I crystallise my proteins(s) using amazing crystallisation robots – these machines can fire a 50 nanolitre drop (50 billionths of a litre) of protein solution accurately onto a spot the size of a pinhead. We can setup thousands of crystallisation experiments every hours – and the more experiments we setup, the more likely we are to be able to grow crystals of our protein!
When we get crystals, we take them to Synchrotrons (mini versions of the large hardon collider – the one near Oxford is “only” 560 metres around, rather than 27 kilometres for the LHC), and shoot these crystals with high powered X-ray beams. This gives us diffraction data which then allows us to figure out what the protein looks like!
Sounds simple. Can take years!
What I'd do with the money
Buy a small tablet and projector to take my “Bluffers Guide to Crystallography” talk on the road!
I’ve given a public engagement talk about protein crystallography a couple of times. So far, this has involved going to “Cafe Scientifique” or “Science Bar” groups. Next Year is the UN International year of Crystallography – I’d like to use the money to take my talk on the road and tell everyone about how awesome crystallography is!
I have also been interviewed about science and crystallography on the Dessert Lionel Discs podcast.
I also tweet incessantly, often about science and Crystallography – @XtalDave
How would you describe yourself in 3 words?
Caffeinated, Curious, Creative.
Who is your favourite singer or band?
What's your favourite food?
I really like bacon. And ginger. In my spare time I am trying to create ginger-flavoured bacon.
What is the most fun thing you've done?
Recent family holiday in Spain – dodging big waves in the surf with my boys!
What did you want to be after you left school?
I didn’t know! Either a Vet or a Scientist!
Were you ever in trouble in at school?
What was your favourite subject at school?
What's the best thing you've done as a scientist?
Seeing structures of proteins that no-one has ever seen before.
What or who inspired you to become a scientist?
My Dad (a Vet) and going to Jodrell Bank Radio Telescope as a kid..
If you weren't a scientist, what would you be?
If you had 3 wishes for yourself what would they be? - be honest!
Happy, Wealthy and Wise.
Tell us a joke.
Neutron walks into a bar, orders a pint of beer and asks how much it costs. Barman says “For you, no charge”
So, if you are chatting with me, or I have been answering your questions, I am most likely sat here
I spend an awful lot of time sat at my computer processing data, but in order to generate data to process, I need to have crystals, like this
– so I need to get myself in the lab! My lab bench is absolutely covered in bottles of reagents that I have made/brought to allow me to do the experiments I want to do – it looks very messy (and it is) but every bottle has a role, and I know where everything is – it’s a bit like organised chaos!
When I’ve made the protein that I want to study, I need to collect some structural data about it – this is what Crystallography is all about – finding out about the structure of molecules that we think are important in whichever disease or process it is that we are studying.
Here is me (fully bearded) setting up to collect X-ray data from a solution of one of my proteins – this is the setup for a technique called “SAXS” (Small angle X-ray scattering) – it is just like Crystallography, but without crystals!
This is useful as it allows us to get some data on proteins that we can’t crystallise, but the data quality is nowhere near as good as Crystallography.
When we get diffraction data from our crystals, we see images containing lots of regularly spaced diffraction spots – using sophisticated, custom-made computer programs, we can generate 3D models of our proteins, which may look a bit like this:
or (better still) we can make animations so that we can better appreciate the 3D nature of the structure:
This is a protein that certain bacteria make that is responsible for gas gangrene!
Having figured out what our protein looks like, we can try and figure out what it does – biology is driven by how molecules interact with each other, so one of the most useful things we can learn is what a protein binds to. This is the biophysics lab at the university of Manchester where I use all sorts of different techniques to look at which proteins my protein binds to, and how it does it!
Once we’ve learned something new, we need to share our results with other scientists – this is mostly done by writing scientific papers, but a much more fun way of sharing is to go to conferences and give presentations about our work to other specialised groups of scientists (I am on the right here – honest!).