The long term objective of this research program is to define the set of regulatory mechanisms which control the behavioral actions of neuromodulators, particularly neuropeptides. Recombinant DNA, immunohistochemical, biochemical and electrophysiological techniques are used to follow the flow of information encoded in neuropeptide genes beginning at the level of gene expression extending to the physiological activities which directly modulate animal behavior. Due to the tremendous numerical complexity and cellular diversity of the mammalian central nervous system, a reductionist approach is appropriate. Two invertebrate systems are for these studies. The fruit fly, Drosophila melanogaster is the most widely studied and best understood eucaryotic organism at the genetic level. A set of peptides related to the four amino acid neuropeptide PheMetArgPhe-amide will be investigated at the genetic, biochemical and behavioral level. The marine snail, Aplysia california has a central nervous system consisting of only 20,000 cells. The cells are large, identifiable and the behavioral roles of many neurons have been established. Many of the large neurons express neuropeptide genes at high levels facilitating studies of proteolytic processing, packaging and transport of the peptide products. Aplysia also offers the opportunity to study molecules which are copackaged with the peptides. Defining the causes of various mental illnesses requires a through understanding of the cell biology of neurons. The fundamental mechanisms used by invertebrate neurons to regulate the actions of neuromodulators are likely to be common to all species including man. Thus these studies will help in providing insight into the mechanisms of psychiatric disorders, thereby moving research efforts closer to effective therapies.
| Misura, K M; Gonzalez Jr, L C; May, A P et al. (2001) Crystal structure and biophysical properties of a complex between the N-terminal SNARE region of SNAP25 and syntaxin 1a. J Biol Chem 276:41301-9 |
| Misura, K M; Scheller, R H; Weis, W I (2001) Self-association of the H3 region of syntaxin 1A. Implications for intermediates in SNARE complex assembly. J Biol Chem 276:13273-82 |
