Profile

Bacteria are rapidly becoming resistant to the drugs we have available and we need to come up with ways of making new drugs, fast.

The importance of antibiotic resistance is highlighted by it’s inclusion in the Longitude Prize (http://www.longitudeprize.org/challenge/antibiotics)

To do try and identify new ways to target bacteria I grow cells that make proteins from superbugs and biological weapons, then I find ways to crystallise them.  These crystals are very small – generally so small you can’t see them with your own eye and you need to use a microscope.  Here are some crystals of a protein called Uridine Monophosphate Kinase – or UMPK for short:

Using these crystals and the very sophisticated equipment at Diamond Light Source, I fire intense beams of light, known as X-rays, at them and measure the scattering of the beams.  This scattering just looks like an arrangement of spots (see below) but thanks to some amazing scientists (William and Lawrence Bragg, Max Perutz and Dorothy Hodgkin, amongst others) some very complex mathematical equations and very powerful computer programmes we can use these patterns to work out the shape and features of the proteins.

Knowing the shape and features of a protein can provide a massive amount of information on how the protein works, how bacteria develop resistance to current drugs, and it can help us develop new drugs for tackling superbugs and biological weapons.

It’s very important to discuss and share interesting results with the scientific community and so sometimes I get to travel to places like San Diego in California and tell people what I have been doing!

Some days I will be doing some synthetic chemistry in a fume hood, making small molecules that we hope could lead to a new drug.

Other days I will be growing bacteria and then I’ll burst them open to get the protein from inside to try and crystallise.  On the most exciting days (or nights) I will head off to Diamond Light Source to fire X-rays at my crystals to try and solve the structure of the protein that the crystals are made off.  Diamond is pretty big circle (around 560 m in circumference) and looks pretty industrial on the inside despite it’s shiny exterior!

The days immediately following trips to Diamond are usually spent at my desk, processing data and trying to solve the structure of my protein.  Using this information, I can design better small molecules which might be better drugs.  Here is a picture of my desk.  On the screens are some protein structures I’m currently working on.

Here is the end product from all of this work.  This is a cartoon of the structure of a protein called MPS1, which is involved in cancer.  I solved this structure as part of my PhD at The Institute of Cancer Research and we are able to use this structure to design potent and selective inhibitors of this protein which could lead to new drugs for treating cancer.

Apart from my lab work, I also help supervise young students in the lab and do a little bit of teaching here and there.