Yvonne Jones: Cancer and Protein Crystallography
Cells communicate through receptors on their surface. Diseases are triggered when these finely tuned systems don’t work correctly. We can now look at the signalling complexes down to the atomic level. This knowledge might help us develop therapies to grow nerve cells through a scar in the spinal cord, stop cancer from growing and spreading, or develop anti-cancer vaccines.
Q: Hello Yvonne. Why is cell-cell communication important for our health?
YJ: Because our bodies are made up of millions and millions of cells and they all need to be able to communicate with each other and work out: are they in the right place, doing the right thing, at the right time? Do they need to move to somewhere different? Do they need to multiply up? Do they even need to die because they are not needed anymore?
Q: What happens when the signalling systems don't work properly?
YJ: One example would be cancer. That is a case where signalling systems aren't working correctly in terms of telling cells not to just carry on growing and multiplying. The particular aspect that I am currently working on is in the latter stages of cancer - metastasis - when cancer cells start moving from that particular tissue where they have started growing to different tissues. So they are no longer staying where they should be, they are invading other parts of the body. That would be one example. Another example would be the immune system not recognising that we have been infected by particular organisms, so the immune cells aren't spotting this fact and fighting things off fast enough.
Q: Could you tell us how cells communicate?
YJ: The way that they do that is through receptors on their cell surfaces - it is like they have got lots and lots of little aerials sticking out from their surface, but in this case they are proteins and what they are doing is waiting to recognise and to dock into proteins either from neighbouring cells or that are secreted by cells. Sometimes over very long distances they build up gradients, so they're acting as messages for cells to grow or divide or, in the case of the cells that I am interested in at the moment, for metastasis for cancer cells, then they are determining this balance between whether a cell is sticking somewhere or whether it is being pushed away and moving off. They are acting as guidance queues, almost like cellular SatNav!
Q: What are the most important lines of research that have developed in the past 5 or 10 years?
YJ: In my view it would be our ability to look at these signalling systems right down to the atomic level detail. It is a bit like understanding how a clock works or how a car works - it is all very well trying to describe it in words, but if you can actually see it in detail, open up the bonnet and see inside at all the different bits of a motor, then you can understand how it works. And once you can understand how it works you have some idea of how you can go in and manipulate it to make it work correctly when things go wrong.
Q: Why does your line of research matter, why should we put money into it?
YJ: Because if we can understand what these things really look like and how therefore they work, then we can go in and either block them in the case of a cell guidance queue that is now acting to guide cells in cancer metastasis to where they shouldn't be in the body, so we want to actually block it. You could design a drug, a small molecule that would go in, fit very specifically the shape of the antennae, the little structure on the cell surface, and block it. Or else in the case of the repair of the spinal cord when there has been serious injury, there the problem is that the nerve cells aren't able to regenerate and grow through the scar. And if we can stop the signals that are stopping them and instead give them signals to encourage them to grow through the scar, then we can help regenerate after damage.
Q: How does your research fit into translational medicine within the department?
YJ: Well obviously what I am doing is very basic research but I can then discuss with my colleagues how my basic insights can feed through to the clinic, and that is one of the exciting things about being part of the Nuffield Department of Medicine. It takes a long time, but one example of something that we have been doing now for over a decade is looking at the way that the cells in the immune system are able to recognise when a cell is infected. In particular we have been looking at how they recognise cancer cells for melanoma, and that is work I'm doing with Enzo Cerundolo who is based at the Weatherall Institute of Molecular Medicine. He is a tumour immunologist, and from taking my basic insights he is now able to work to try and improve anti cancer tumour vaccines which can be given to patients when they have got melanoma as one of the ways of trying to combat it.