Favourite Thing: The discovery moment – which is usually our first glimpse of the structure of a protein molecule that no-one has ever seen before. Magic!
Me and my work
I study the molecules of life and death in glorious detail in three dimensions
I am a ‘protein crystallographer’. This means that I use X-rays and crystals to reveal the structures of protein molecules, which are among the most interesting molecular machines that keeps cells and anything made of cells (i.e. you!) ticking over.
Proteins do all sorts of interesting things, including digesting your dinner, carting oxygen or fat around the body or allowing ions to flow in brain cells so that you can think. They are often involved in disease, either when they malfunction or if they are working for pathogens such as bacteria or viruses. A lot of our work at the moment is devoted to looking at virus proteins. One of our main interests is the foot-and-mouth disease virus, which causes a very nasty disease in farm animals.
To really understand how proteins work, and to be able to think of new ways of treating disease, we need to know what they look like. In fact we need to see exactly how the molecules are built up from atoms. Unfortunately, we can’t use microscopes since they can’t seen things that are smaller than the wavelength of light (0.0005 mm) and proteins (and atoms) are much smaller than that.
Instead we use a very energetic form of light—X-rays—in a rather unusual way. To study a particular protein, we need to produce a few milligrams of a highly purified sample—this is normally done by genetic engineering–and then try to grow a crystal of the purifed protein (like the ones in the photo above).
We then fire a beam of X-rays at the crystal and can record images like this:
It looks odd, doesn’t it? The spots that you can see on the detector make up a diffraction pattern and look nothing like a molecule. But we can use maths to work out the relationship between the pattern of spots and the structure of the protein that the crystal is made up of. We get computers to analyse the data so that we can determine the structure of the protein. In 3D!
The structures can look a bit complicated because protein molecules typically contain several thousand atoms:
But we try to simplify the view so that people can figure out what is going on. Here’s a more schematic view of the same protein – it’s called the 3C protease from foot-and-mouth disease virus:
What you can see is that the 3C protease (coloured green and purple) is sticking to part of another protein (orange) which it is about to cut into two pieces. Cutting up proteins is one of the jobs that the virus needs to do to build new copies of itself in infected cells.
We study lots of different proteins in this way—to figure out how they work. Sometimes we can use this information to try to come up with ways to stop the proteins from working, especially if they are causing disease.
Anyway, that’s enough words. Here’s a short film I made in 2008 to explain why we are working on the 3C protease from foot-and-mouth disease virus. The cool bit is 2 minutes in… Enjoy! (If YouTube is not available to you, try here).
My Typical Day
In and out of my office writing emails, papers and grant applications, teaching and talking to students and my research team.
Is it too much of a cliché to say, there’s no such thing as a typical day? (Answer: yes). But one of the great things about working a scientist is the variety of things that you get involved in. Since I am a group leader, I don’t actually spend much time doing experiments. I supervise PhD students and research assistants (scientists who already have a PhD), helping them to plan experiments, interpret their results and to solve technical problems. Lots of experiments don’t work first time around, so there’s usually plenty of trouble-shooting.
I am also responsible for making sure that we have enough money to keep running. This means applying for grants, either from the government-funded research councils or charities such as the Wellcome Trust. This is a very competitive process — there are lots of scientists applying for money. Usually only about 20% of applications are successful. Imagine sitting an exam where the teacher told you only the top 20% were going to pass… Stressful!
Since I am employed by a university I also have to teach. Mostly this involves lectures on biochemistry to first, second or third year students. Please don’t tell them that my degree is in Physics and that I only have GCSEs in Biology and Chemistry!
I do like getting up in front of a class and lecturing. But marking exam scripts — there are about 130 student in our classes — is really, really boring.
For me the really fun part of the job is when you have new results to think about and especially when someone on the team has solved a new structure. That’s really exciting because suddenly—and for the very first time—we can see a part of nature that always been hidden from us. That makes the job a real voyage of discovery.
It’s also nice when I get to travel abroad to do experiments (at synchrotrons) or to go to conferences to talk about our work.
At the end of the day I have three teenage kids to keep me busy. But I still manage to find a bit of time for my latest ‘craze’ – astronomy. I got a telescope for Christmas and have been getting to know the moon and the night sky. Here’s a picture I took recently:
What I'd do with the money
Make more videos about the *reality* of science – the good, the bad and the ugly!
**UPDATE (21 June 2010)** Please have a look at the trailer to the film I propose to make if I am lucky enough to survive the 2nd week. Enjoy!
I’ve made just a couple of videos trying to reveal the science that we do (one of them explanatory, one about our experiences at the synchrotron and one just for fun*). I would like to be able to buy props or equipment to make more. I think I’d like to combine some science with interviews with other scientists, at all levels, to explore why they got it. One of the things I’d like to able to show is that you certainly don’t have to be a genius to make a significant contribution to scientific research. I think a good way to do this would be to interview members of my group and other scientists from around the country.
However, I’d be very happy to get suggestions from students about possible video projects.
*If you can’t access YouTube, you may be able to view the videos on page on my web-site at Imperial.
How would you describe yourself in 3 words?
My wife, whose judgement I trust totally, said “Grumpy, funny and kind”. Um, let’s start with that. Quiet at the back there!
Who is your favourite singer or band?
That’s a tough one. I can’t decide between U2/Van Morrison/Talking Heads!
What is the most fun thing you've done?
This question really made me think – and realise that I’m probably working too hard. The most fun things I’ve done recently were seeing comedian Mark Watson perform live stand-up and seeing the surface of the moon through a telescope for the first time. By far the most exciting experiences of my life were the births of my three children, especially the last one who decided to arrive before the mid-wife so I had to deliver her myself!
If you had 3 wishes for yourself what would they be? - be honest!
1. Lots of money for research. 2. Travel into space (nothing too ambitious – a ticket on Virgin Galactic would do). 3. The chance to direct a movie.
What did you want to be after you left school?
Believe it or not, I was really torn between doing science and going into the church. You can probably see how that one turned out…
Were you ever in trouble at school?
Shamefully, almost never. Was once branded ‘one of the most irresponsible boys in the 6th form’ but only by a headmistress with no sense of fun!
What's the best thing you've done as a scientist?
I get a huge kick out of solving a new protein structure – it makes me feel like a heroic explorer of the unknown, to see a piece of the universe that no-one else has ever seen before..
Tell us a joke.
Two beavers are looking up at a massive hydroelectric dam. “I didn’t build it,” says one, “but it is based on my idea!”
All Saints Primary School, Ballymena (1968-75); St Louis Grammar School, Ballymena (1975-82)
1982-85 Imperial College London – Physics BSc
1985-88: PhD in Biophysics at Imperial College; 1989 NHS (a disaster!); 1989-1995 Research assistant in France, UK and USA
Imperial College London
Professor of Structural Biology: Research and Teaching