The molecular mechanisms of odorant recognition and discrimination (olfaction) are poorly understood. The long term objectives of this work are the identification and characterization of the genes and molecules that confer specificity to odorant recognition and signal transduction in C. elegans. These molecules should include the odorant receptors themselves, which have not been identified in any animal. Studying ,the regulation of signal transduction may elucidate its role in development and neural signalling, and its disruption in cancer. Odorant responses of C. elegans will be studied at the behavior, cellular, genetic, and molecular levels. The chemosensory cells that recognize each of the different categories of odorants will be defined by laser ablation of identified neurons. These experiments will show how chemosensory information is sorted and encoded by sensory neurons. Mutants with defects in the responses to the volatile odorants benzaldehyde and diacetyl will be sought. These and existing mutants defective in odorant responses will be characterized genetically and behaviorally to determine which might bear mutations in odorant receptor genes, which affect the signal transduction and integration processes, and which affect the development of the chemosensory neurons. Molecular clones of the odr-2 gene will be isolated. Based on genetic and behavioral criteria, odr-2 seems likely to be involved in the response to specific odorants. The sequence of odr-2 and its pattern of expression in wild-type and mutant animals will be determined. This analysis will determine the molecular basis for the genetic function of this gene. We will also clone the gene(s) that are the strongest candidates for odorant receptors, based on genetic analysis. Finally mutants defective in the ability to discriminate among different attractants will be sought; these mutations may affect the regulation and integration of chemosensory information.