Similar approaches are being used to determine the primary components in the signaling pathways of the epidermal growth factor receptor and related tyrosine kinases. Cellular physiology and, in particular, the role of calcium in stimulus-secretion coupling in cells in the immune system are being studied. Biophysical, biochemical, and pharmacological approaches are being used to examine the receptor for immunoglobulin E on mast cells and the signal transduction mechanisms leading to an increase in intracellular calcium and the release of mediators of allergic reactions. A laser-pulse photolysis technique, using photolabile precursors of neurotransmitters synthesized by the laboratory, with a microsecond time resolution, is used. Effects of receptor malfunction in nervous system disease and of therapeutic agents and abused drugs on the receptors are investigated.
Drug design involving combinatorial synthesis is based on the mechanistic studies.
The photolabile neurotransmitter precursors are also used to map neuronal circuits controlling measurable responses in Caenorhabditis elegans . Investigation of the regulation and mechanisms of exocytosis in different cell types, including nerve terminals, chromaffin cells, and granulocytes. Focus is on measuring exocytosis of single vesicles to study the mechanisms of and relations between docking, fusion pore formation and expansion, and transmitter release. Methods include patch clamp capacitance measurements, amperometry, patch amperometry, fluorescence microscopy, computer modeling, optical trap, molecular biology, and biochemistry. Investigations are being made on the molecular and biophysical characteristics of excitatory amino acid-activated ion channels in primary neuronal cultures and in transfected cell lines.