Watching Cancers At The Nano-scale
Chris - Tell us about your work, literally zooming in and seeing things on the microscopic level and cancer in action.
Stephen - That's right. In many cancers there's a molecule called epidermal growth factor receptor involved. You may well have heard about herceptin in the news recently. It's involved in one of a family of four molecules of which epidermal growth factor receptor is one. What happens in order for the cell to divide is that a signal has to come in in the form of a molecule from another cell. This molecule attaches itself to the epidermal growth factor receptor on the cell membrane. When that happens, there is a change in the shape of the receptor molecule. It would be possible if we knew exactly what the change in shape was and how it progressed in time for somebody else to take this knowledge away and design a drug which prevented it.
Chris - In other words, just block up the receptor so that the cancer cell doesn't hear that signal.
Stephen - Yes, and this is a normal process. It happens in all our cells anyway, it's just that it basically goes into overdrive in cancers. So what we can do to exactly see what this change of shape is, is to attach little fluorescent tags to different parts of the receptor molecule. There are things like green fluorescent protein (GFP) that's been extracted from jellyfish and you can stick that into the molecule. You can attach quantum dots, which are little cadmium selenide molecules. These are very small little nanoparticles, which you can tag onto the different parts of the receptor molecule. If we excite them with a laser, they will then emit fluorescence and the wavelength of the fluorescence that's emitted and the polarisation of the fluorescence gives us information both on the distances and angles between different fluorescent tags on different parts of the molecule.
Chris - So you can begin to build up a three-dimensional picture of what this docking station receptor looks like on the cell surface.
Stephen - That's right. The idea is that in real time we can see exactly the change sin shape that are occurring in this molecule.
Chris - And what about if you throw a drug on. Does it tell you about what happens to the receptor when they're present?
Stephen - That's the idea in the future. Herceptin only works on HER2 of this family of four molecules. All four molecules are involved in different cancers and we want to study all of them.
Chris - So you've been able to label individual parts of the receptor in order to see how they all interact. How is this going to translate into a new form of herceptin and in what sort of time scale? How is this better than the traditional way of doing things?
Stephen - The receptor molecule itself and its structure has been studied using things like x-ray crystallography. This gives you a static picture of what the molecule looks like and it tells you what it looks like in solution rather than in an actual cell, which is a completely different thing altogether. What we can do is look at the receptors in real cells and in real time. Hopefully this will be a quicker and more physiological method of getting the basic science necessary in order to design a drug. You could study how the drug was working and how effective it is by using these microscope methods as well.