Phosphoinositide Signaling in Mammalian Olfaction

气味在我们的生活质量和健康中扮演着越来越重要的角色，但这一角色却被疾病、药物、衰老和环境对嗅觉能力的影响所削弱。初级嗅觉受体神经元起着检测和传导气味刺激的关键作用。任何导致受体细胞激活的细胞过程的破坏都会损害嗅觉功能。我们的实验室正在进行一项由美国国立卫生研究院资助的研究项目，研究以龙虾为动物模型的嗅觉转导机制。利用从龙虾模型中获得的见解，我们假设通过探索3-磷酸肌肽途径的潜在参与，我们可以在哺乳动物中暗示磷酸肌肽信号。在这样做，我们将重新访问重要的，但有争议的问题的作用，如果有的话，磷肌肽信号在哺乳动物嗅觉转导。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成围绕哺乳动物模型，特别是小鼠和大鼠的单独调查。由于这是我们实验室对哺乳动物模型的第一次冒险，我们认为在将这条调查线作为R01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。这条令人兴奋的新研究路线将对该领域产生重大影响，一旦拟议的额外初步数据到手，它将有竞争力获得R01资助。

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.