||Department of Biology, University of York|
|2004 - 2006
||University of Edinburgh|
|1999 - 2004
||University of Liverpool|
||University of Dundee|
||University of Bath |
Research in my lab focuses on the regulation of neuronal function by protein phosphorylation:
(1) The function of the neuronal isoforms of Src tyrosine kinase. The neuronal splice variants of C-Src, N1- and N2-Src, are exclusively expressed in neurons but no specific neuronal function has been attributed to either kinase. Interestingly, the N-Srcs have short inserts in their SH3 domains which dramatically affect their biochemical properties. Clues as to the function of these enzymes are being obtained by discovering their neuronal substrates.
(2) Presynaptic cAMP-dependent signalling in the cerebellum. The activity of parallel fibre synapses in the cerebellum regulates motor learning and co-ordination. cAMP enhances the activity of parallel fibre synapses by increasing neurotransmitter release via PKA phosphorylation. Visualisation of neurotransmitter release and Ca2+ in cerebellar neurons by real time fluorescence imaging is being used to study the cAMP signalling events responsible for regulating presynaptic activity.
We have developed a method for the simultaneous live imaging of neurotransmitter release and calcium influx in cultured neurons. This technique allows us to study the coupling of calcium to neurotransmitter release in individual synapses, which has implications for regulating synaptic strength in processes such as learning.
|Postdoctoral fellow (Full time)
||Dr Chris Dunning
||Function of the neuronal tyrosine kinase N2-Src in synaptic vesicle exocytosis |
||Structure-function studies of the neuronal Src tyrosine kinase|
Mechanisms of silent synapse activation in learning (for 2012 - 13)
It is accepted that learning in the brain involves creating new synapses or increasing the activity of existing synaptic connections between neurons. A subset of synapses are ‘silent' and have no detectable activity under resting conditions but can be switched on by stimuli that mimic learning. A large proportion of synapses in the adult brain are thought to be silent, and therefore a detailed knowledge of silent synapse activation could give important insights into the mechanisms of learning and memory. We have shown that presynaptic silent synapse activation is mediated by protein kinase A (PKA) and this project will focus on the signalling pathway downstream of PKA. Using a wide range of proteomic and cell biological techniques, we will identify presynaptic targets of PKA responsible for silent synapse activation. Promising targets will be characterised using a real-time imaging assay of silent synapse activation in cultured neurons.
References: Cousin and Evans (2011) J Physiol, 589:1943–1955; Evans (2007) Biol Cell, 99: 363–78.