Phosphoinositide Signaling in Mammalian Olfaction

气味在我们的一般生活质量和健康中发挥着越来越重要的作用，这种作用受到疾病，药物，衰老和环境对嗅觉能力的冲击的影响。初级嗅觉感受器神经元具有检测和传导气味刺激的关键功能。 任何导致受体细胞活化的细胞过程的破坏都会损害嗅觉功能。 我们的实验室保持着一个正在进行的NIH资助的研究计划，以龙虾为动物模型，研究嗅觉传导的机制。 利用从龙虾模型中获得的见解，我们假设通过探索3-磷酸肌醇途径的潜在参与，我们可以牵连在哺乳动物中的磷酸肌醇信号。 这样做，我们将重新访问的重要，但有争议的问题的作用，如果有的话，磷酸肌醇信号在哺乳动物的嗅觉转导。 与另一个实验室合作获得的初步数据支持这一论点。 我们建议将这一重要发现发展为围绕哺乳动物模型（特别是小鼠和大鼠）建立的独立调查线。 由于这是我们实验室首次尝试哺乳动物模型，因此我们认为在将这一研究线作为R 01提交之前，更好地记录我们使用哺乳动物模型的能力是明智的。这一新的、令人兴奋的研究领域应该会对该领域产生很大的影响，一旦获得了拟议的额外初步数据，它将成为R 01资金的竞争对手。

Odors play an increasingly appreciated role in our general quality of life and well being, a role that is compromised by the effect of disease, drugs, aging and environmental onslaught on olfactory competence. Primary olfactory receptor neurons serve the critical function of detecting and transducing odor stimuli. Disruption of any of the cellular processes leading to receptor cell activation would impair olfactory function. Our laboratory maintains an ongoing NIH-funded research program on mechanisms of olfactory transduction built around the lobster as an animal model. Using insight gained from the lobster model, we hypothesized that by exploring the potential involvement of the 3-phosphoinositide pathway we could implicate phosphoinositide signaling in mammals. In doing so, we would re-visit the important, but controversial question of the role, if any, of phosphoinositide signaling in mammalian olfactory transduction. Preliminary data obtained in collaboration with another laboratory support that contention. We propose to develop this important finding into a separate line of investigation built around mammalian models, specifically mouse and rat. As this is the first venture of our laboratory into mammalian models, we feel it prudent to better document our ability to work with mammalian models before submitting this line of investigation as an R01. This new, exciting line of investigation should have high impact on the field, making it competitive for R01 funding once the proposed additional preliminary data are in hand.