STTR Phase I: Odorant receptor identification transforms odor design

这个小型企业技术转让(STTR)第一阶段项目的更广泛的影响/商业潜力将是开发气味受体功能生物测定，为开发和配制用于多种商业产品的气味的公司提供服务。这些服务识别负责特定气味感觉的生物传感器，并确定这些传感器如何参与气味之间的相互作用。有了这些知识，几件事成为可能。与想要的嗅觉相关的传感器可以直接定向，促进设计令人愉悦、舒缓或刺激的气味的配方。对令人厌恶的气味做出反应的传感器也可以被识别出来，这为开发这些攻击性刺激的特定阻滞剂开辟了道路。此外，可以表征气味之间发生的高度不可预测的相互作用，并可以识别受这些相互作用影响的传感器。这使得有可能预测混合气味的结果，促进为特定目的设计的新气味的开发。就像了解体内信号分子的作用导致更好的药物开发一样，这些服务将允许更好地操纵气味环境和体验。这一STTR第一阶段项目建议完成两种生物测试的开发，这些测试能够识别和表征对任何气味做出反应的传感器。人类和动物使用了数百种气味感应器蛋白，但对任何给定的气味都有哪些反应尚不清楚。一个主要目标是改进体内测试，以识别哪些传感器对气味做出反应，从而提高其快速筛选气味的灵敏度和能力。这一目标测试了旨在减少变异性的新的分析条件和量化传感器响应的新方法。同样重要的是一项概念验证实验，旨在证明特定传感器蛋白上的气味之间的相互作用可以在体内测量。初步结果支持这样的预期，即实现这些结果将是可能的。另一个目标是将药物的细胞培养试验转变为能够测量单个传感器蛋白对气味的敏感性的试验。这一目标测试了促进这些传感器在细胞培养环境中发挥作用的新方法。细胞培养试验的成功转换取决于从几十个候选者中找到正确的辅助因素组合。

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project will be to develop odorant receptor function bioassays to provide services for companies that develop and formulate odors used in many kinds of commercial products. These services identify the biological sensors responsible for specific odor sensations and determine how these sensors are involved in interaction effects between odors. Armed with this knowledge, several things become possible. The sensors associated with desirable smell sensations can be directly targeted, facilitating the formulation of odors designed to please, sooth, or stimulate. The sensors that respond to repulsive odors can also be identified, opening the way to develop specific blockers of these offensive stimuli. Furthermore, the highly unpredictable interactions that happen between odors can be characterized, and the sensors affected by these interactions can be identified. This makes it possible to predict the outcome of mixing odors, facilitating the development of new odors designed for specific purposes. In the same way that understanding the actions of signaling molecules in the body led to the development of better pharmaceutical drugs, these services will allow better manipulation of odor environments and experiences. This STTR Phase I project proposes to complete the development of two biological assays capable of identifying and characterizing the sensors that respond to any odor. Humans and animals employ hundreds of odor sensor proteins, but which respond to any given odor is unknown. One major objective is to improve an in vivo assay that identifies which sensors respond to an odor, increasing its sensitivity and capacity for screening odors rapidly. This objective tests new assay conditions designed to reduce variability and new ways to quantify the responses of the sensors. Also important is a proof-of-concept experiment designed to demonstrate that interactions between odors at specific sensor proteins can be measured in vivo. Preliminary results support the expectation that achieving these results will be possible. Another objective is to convert a cell culture assay for drugs into an assay capable of measuring the sensitivity of individual sensor proteins to odors. This objective tests new ways to facilitate the function of these sensors in the cell culture environment. Successful conversion of the cell culture assay depends on finding the right combination of accessory factors from among a few dozen candidates.