We are using the unicellular eukaryote Tetrahymena as a model sensory cell to study the chemosensory pathways involved in cellular responses to depolarizing chemorepellents (such as ATP, GTP, and polycations like lysozyme) and chemoattractants (like lysophosphatidic acid) as well as the mechanisms responsible for adaptation to these stimuli. We use targeted gene knockouts to study the involvement of GPCRs (G-protein coupled receptors), their G-proteins and other parts of their chemosensory transduction pathways. We incorporate intracellular electrophysiology, immunolocalization, intracellular Ca++ measurements, RT-PCR, quantitative PCR and other biochemical assays to further understand the pathways and responses of mutants and wild type to these stimuli. We also work in collaboration with several other labs to study the effects of knockout mutations on ciliary waveform, ciliary reversal and ciliary beat frequency. One of the main goals of this work is to see how similar the receptors and sensory response pathways of this simple eukaryotic cell are similar to those of higher organisms. This may allow us to use Tetrahymena as a more humane model system to gain insights into how humans and other organisms respond to chemical stimuli.