Ground control to Major Tom.

In the last post, I mentioned that I work on exploring the complex network of interactions between genes, proteins and microRNAs that mediate a cells response to its environment. This field is known as cell signalling and the possible routes through the network are signalling pathways.

To give you an example of how a typical pathway might work, suppose a cell is attacked by a virus. The virus might emit a protein that the cell, over millions of years of evolution, has learned to recognize as indicative of that threat. In this case, it will have evolved so that the viral protein binds to another protein on the cell surface, triggering a cascade of protein-protein and protein-gene interactions within the cell. The triggering happens because the binding causes a third protein to detach from the interior of the cell surface, which then floats off into the cell interior. Along the way it interacts with many other proteins in a huge variety of ways. For example, it might bind to another protein in such a way that causes the bound pair migrate towards the cell nucleus, before binding to a third protein that allows the bound state to pass into the nucleus. Once there, the three bound proteins could separate and one could then bind to a different protein, causing the travelling protein to change its configuration. After the change, the reconfigured protein might detach itself and bind to a gene, instigating the manufacture of a new protein. Perhaps the new protein binds to another gene, triggering the production of another new protein and, as the last link in the chain, this protein could be shuttled to the cell surface in order to help with the fight against the virus.

Whilst this is a wildy hypothetical example, its also wildy over simple. Real pathways are much more complicated. The reality is that they contain ten times to a hundred times more proteins and genes and exploit feedback to create complex patterns of signals. Studying these signals is complicated further by the dramatic interweaving between different pathways. Cell's don't conveniently mediate their signals with a set of distinct pathways, insulated from each other. The various pathways have a significant overlap and for a given triggering protein, there will be many stimulated pathways.

All this makes it damn hard to study what's going on in a cell. At the outset, you have no clue about how the network or pathways works and its only through expensive and time consuming experiments that this picture can be put together, literally one link at a time. The whole process is like trying to assemble a 10,000 piece jigsaw with no picture on the box.

But despite the overwhelming scale of the challenge, we persevere because there is the potential to exploit the pathway structures to develop extraordinary medical therapies. By understanding these tapestries of pathways, we can learn how to correct the malfunctions cause disease. This will lead us to better designed treatments that have a maximised impact on the ailment with a minimised number of side effects. Viva la revolution!

If you'd like to read more about cell signalling, here's a good review in Nature.