My research is concerned with the biological chemistry and molecular physiology of signaling in the nervous system. Our approach is to examine mechanisms by which paralytic venoms disrupt synaptic transmission. Spider and scorpion venoms are cocktails of toxins which immobilize prey through specific actions on ion channels in nerve membranes. The ability of many toxins to discriminate between different ion channel subtypes makes them valuable as pharmacological probes for functional analysis. Current research efforts include the isolation and identification of novel toxins and analysis of their structure-activity relationships by site-directed mutagenesis and patch clamp electrophysiology.
Applications of specific toxin-receptor interactions are being found in both medicine and agriculture. Certain highly selective toxins can have therapeutic actions with minimal side effects. Specific ion channel modification by chemical agents such as toxins or drug mimics is emerging as a strategy for treatment of stroke, convulsive syndromes and chronic pain. Likewise, ion channel-specific toxins are finding applications in agricultural pest control strategies. Many toxins are shown to specifically target insect ion channels. Genes for these toxins, when genetically engineered into insect-specific pathogens, constitute novel biological insecticides.
A second major research focus is on neuropeptides that regulate developmental and behavioral processes. The recent discoveries of the epitracheal endocrine system in insects and its secretory product, the ecdysis-triggering hormone (ETH), have revealed new insights into the endocrinology of ecdysis, the crucial stage through which insects must pass repeatedly during development from embryo to adult. ETH triggers a series of complex centrally patterned motor behaviors leading to ecdysis and thus provides an excellent model system for examining the relationships between gene expression, development, and animal behavior.