Pamela England, PhD

Chemical Neurobiology: Ion Channel Structure-Function, Synaptic Plasticity

One of the most amazing properties of the mammalian central nervous system is its ability to process and store information. Changes in the strength of synapses appear to underlie such learning and memory. Major research efforts in our group are directed towards understanding the molecular basis for this synaptic plasticity. We use a combination of synthetic organic chemistry, biochemistry, molecular biology and electrophysiology in our research.

Current Projects

1. One project in the lab seeks to evaluate the roles of phosphorylation of glutamate-gated ion channels. These ligand-gated ion channels have been shown to play a key role synaptic plasticity and have been identified as targets for a variety of serine kinases. Conventional methods for characterizing the effects of protein phosphorylation do not include a way to precisely control the timing of this modification. We are using unnatural amino acid mutagenesis to site-specifically incorporate caged (light sensitive) analogs of serine and phosphoserine at individual phosphorylation sites within glutamate receptors. Flash photolysis (millisecond time scale uncaging with ultraviolet light) of the resulting mutant receptors is used to precisely control the initiation of receptor phosphorylation and phosphorylation-dependent events.
2. A second project in the lab seeks to identify the direct substrates for protein kinases implicated in memory formation. The most extensively studied model for memory formation is the long-term strengthening or potentiation (LTP) of synapses in the mammalian hippocampus following brief periods of high frequency activity. Protein kinases are among the 100 or so molecules suspected to underlie this form of synaptic plasticity. We are using methodology developed by the Shokat Lab at UCSF to identify the direct substrates for protein kinases implicated in hippocampal LTP. In this way we will sort out the cellular signaling cascades underlying memory formation.

Lab Website