Dr Paul Skehel is a senior lecturer in the University of Edinburgh’s Centre for Integrative Physiology.
Human bodies are built from hundreds of different types of cells. The shapes and properties of these cells differ depending on what part of the body they help to form. The cells of the nervous system have a huge diversity of different shapes and properties. Nerve cells make specialised contacts, called synapses, with other nerves and other cells types. We are interested in how these contacts are formed and maintained.
UNRAVELLING SYNAPTIC PROTEIN MUTATIONS
Everyone carries a very small number of mutations in their genome that are not present in the genes of either parent. We think that these de novo mutations most likely arise during the production of the egg and sperm. If a person has a condition such as intellectual disability, but neither parent are similarly affected, then it is possible that a de novo mutation is responsible. Several such mutations have been identified in genes that encode proteins forming the synaptic structures that mediate communication between neurons.
In collaboration with colleagues in the Patrick Wild Centre, we are studying the properties of de novo mutations in synaptic proteins that have been implicated in autism spectrum disorder (ASD), intellectual disability and epilepsy.
Together with Giles Hardingham, David Wyllie and Katie Marwick, my lab is using molecular and electrophysiological methods to investigate the properties of mutations in the NMDA family of glutamate receptors that have been identified in people suffering from ASD, intellectual disability and epilepsy.
We also work in collaboration with Peter Kind, David Wyllie and Lindsay Mizen on the molecular biology of another synaptic protein called SynGAP. SynGAP is produced in several subtly different forms, and the exact function of these proteins is not yet clear. Previous work however has suggested that the different forms of SynGAP can modulate the activity of neurons during critically important periods of development. Again, genetic mutations in SynGAP have been found in people with ASD and intellectual disability, and we hope that through studying how these mutations affect SynGAP we may understand better how the properties of synapses are regulated during development.