Grant: Project Grant

The human nervous system is bewilderingly complex. There are over 100 billion nerve cells, but this is just the start of the complexity. The key properties of the nervous system - eg how we respond to stimuli or coordinate our movement - come not from single nerve cells but from the ways they connect with eachother and there are over a trillion such connections in the brain. This raises key challenges. We can understand how cells divide or make energy by studying single cells in a dish, but we cannot understand how the nervous system works by studying a single nerve cell - we need to know how they are connected and how they talk to each other. Rather than study the complex human nervous system, we turn to a simpler nervous system. The nematode worm C.elegans has just over 300 nerve cells - crucially, every connection between them is known and it is the best characterised nervous system of any animal. We study how perturbing the nervous system either with drugs or with genetic mutations affects worm movement. To do this, we built a system for measuring worm movement in a very rapid way - this system is unique to our group. This lets us examine many thousands of mutant worms to look for changes in movement. Crucially, we can use combinations of drugs, or combinations of mutants to look for examples where one pathway appears to affect another, showing cross-talk. We used this system to discover a new crosstalk between nerve signaling pathways. One signal rapidly affects movement, while a second signal slowly shut this down again. Now we want to understand exactly how this cross talk works. Do these pathways affect eachother in the same nerve cells or does one nerve cell talk to another? What are the genes involved? If we understand how these pathways interact in worms, we may be able to regulate them in humans, where they play key roles in multiple disorders of the nervous system.