Description of Research Expertise

RESEARCH INTERESTS
Molecular mechanisms of regulation of neuronal excitability; modulation of neuronal ion channels; role of ion channel modulation in behavior

RESEARCH TECHNIQUES
Molecular, biochemical and biophysical characterization of ion channels and associated signaling proteins; antibody generation and characterization; co-immunoprecipitation; molecular cloning and mutagenesis; mammalian cell culture; bacterial and mammalian cell expression; yeast two-hybrid screens; patch clamp and voltage clamp analysis of ion channel activity in neurons and heterologous cells; Drosophila genetics, electrophysiology and behavior

RESEARCH SUMMARY
My laboratory is interested in the long term regulation of neuronal excitability and synaptic transmission. We study the molecular mechanisms that nerve cells use to modulate the activity of individual ion channels, since these mechanisms must contribute to long term changes in neuronal function and ultimately in behavior. The essence of our approach is a combination of biochemistry, molecular biology, genetics and electrophysiology, at the level of individual neurons, synapses and ion channels. We study the electrophysiological properties of native channels in neurons, and of cloned channels expressed in heterologous host cells, using patch recording techniques. In parallel we carry out biochemical measurements of channel proteins, making use of specific antibodies directed against channel epitopes. One theme that we are pursuing vigorously is the idea that channels do not exist on their own in the plasma membrane, but rather are part of a regulatory complex that includes signaling proteins that are involved in the modulation of channel function. For example, we have found that the Src tyrosine kinase, the catalytic subunit of cyclic AMP-dependent protein kinase and the ubiquitous calcium sensor calmodulin all bind directly to potassium channels and influence their function. We also have isolated a novel protein named Slob, which binds to and modulates the Slowpoke calcium-dependent potassium channel. We are investigating the molecular details and physiological significance of the dynamic interactions of Slob, the protein kinases, calmodulin and other signaling proteins with several different kinds of potassium channels. One way we do this is by using genetics to introduce mutant channels and their binding partners into flies and ask questions about the roles of ion channel regulatory complexes in neuronal physiology and behavior.