Sensory Transduction in the Vomeronasal System

描述（由申请人提供）：哺乳动物的嗅觉系统包括 至少两个功能不同的器官，主嗅上皮和 犁鼻器（VNO）。VNO是位于喙部的一对管状结构 鼻腔末端，被认为是介导信息素，化学物质 调节生殖和社会行为以及神经内分泌的信号 status. VNO中的感觉传导与主要的感觉传导不同。 嗅觉上皮，仍然知之甚少。描述的实验 在这项授权将测试的假设，感觉转导的VNO是 由类似于介导光转导的信号通路介导 在无脊椎动物中。为了支持这一假设，我们最近发现了一个VNO- 果蝇光激活通道（dTRP）的特异性同源物（TRP 2）， 高度定位于大鼠犁鼻感觉神经元的感觉微绒毛。的 拟议的研究旨在阐明TRP 2通道在以下方面的作用： 犁鼻感觉转导，并在VNO介导的行为。一个核心目标 这项工作的重点是确定激活TRP 2的第二信使途径。 在果蝇中的广泛研究表明，dTRP的激活是下游的， 磷脂酶C，但直接刺激开放dTRP通道是不是 知道的我们将使用膜片钳记录技术和比率Ca++ 在异源细胞类型中成像以研究TRP 2响应于 受体介导的磷脂酶C刺激和直接应用 第二信使第二个目标是确定其他组件 感觉传导级联反应。 这位候选人利曼博士最近加入了牛津大学的教师队伍。 南加州，她是那里的助理教授。伊萨大大 通过给予候选人急需的时间来促进其职业发展， 建立了强大的研究计划，涉及各种复杂的 技术.候选人是一位经验丰富的电生理学家， 分子生物学家，和研究提出将利用她 这些不同的技术来解决生物学中的基本问题 犁鼻系统

DESCRIPTION (provided by applicant): The mammalian olfactory system consists of at least two functionally distinct organs, the main olfactory epithelium and the vomeronasal organ (VNO). The VNO, a pair of tubular structures at the rostral end of the nasal cavity, is thought to mediate detection of pheromones, chemical signals that regulate reproductive and social behavior and neuroendocrine status. Sensory transduction in the VNO is distinct from that in the main olfactory epithelium, and remains poorly understood. The experiments described in this grant will test the hypothesis that sensory transduction in the VNO is mediated by a signaling pathway similar to that which mediates phototransduction in invertebrates. In support of this hypothesis, we have recently found a VNO- specific homolog (TRP2) of the Drosophila light-activated channel (dTRP) that is highly localized to sensory microvilli of rat vomeronasal sensory neurons. The proposed research is aimed at elucidating the role of the TRP2 channel in vomeronasal sensory transduction, and in VNOmediated behaviors. A central goal of this work is to identify second messenger pathways that activate TRP2. Extensive studies in Drosophila, suggest that activation of dTRP is downstream of phospholipase C, but the direct stimulus for opening dTRP channels is not known. We will use techniques of patch-clamp recording and ratiometric Ca++ imaging in heterologous cell types to study gating of TRP2 in response to receptor-mediated stimulation of phospholipase C and direct application of putative second messengers. A second goal is to identify additional components of the sensory transduction cascade. The candidate, Dr. Liman, has recently joined the faculty at the University of Southern California, where she is an assistant professor. This ISA will greatly enhance the candidate's career development by allowing her much needed time to set up a strong research program, involving a variety of sophisticated techniques. The candidate is an experienced electrophysiologist as well as a molecular biologist, and the research proposed will take advantage of her expertise in these disparate techniques to tackle basic questions in the biology of the vomeronasal system.