BRAIN EAGER: Solving the Code of Olfaction Using Nano-Robot Switchable Odorants

小(嗅觉)的感觉蕴含着一个重大的谜团：没有任何科学家或香水师可以通过观察一个新分子结构来预测它的气味或分子结构。该项目旨在开发与鼻子中单个嗅觉感受器结合的分子，从而帮助解决气味导致气味感知的密码。拟议的方法具有广泛的影响和应用：它可能为将气味引入日常设备铺平道路。散发气味的电视、电脑游戏机、手机等的想法已经存在了一段时间。然而，这一目标仍然没有实现，主要是因为“简单的”技术原因：即使一个人成功地制造了一个气味发射设备，然后人们又如何处理发出的气味呢？例如，一款赛车电脑游戏可能会发出橡胶轮胎燃烧的气味，但如何才能从房间里疏散燃烧橡胶的气味？此外，鉴于气味挥之不去，人们如何才能迅速从一种气味切换到另一种？这里提出的技术可能会解决这些问题，因为它将需要无味的颗粒，但随着外部可快速切换的电场的作用，它会呈现出特定的气味。如果成功，拟议中的机制将推动气味设备的革命。此外，这种“可切换的化学物质”方法将可扩展到大脑中的其他受体，并可用于询问有关情绪、感觉运动协调、记忆和学习的基本问题，以及开发与受体信号失灵相关的疾病的潜在新疗法。为了开发一种解决嗅觉组合密码的方法，巴切莱特实验室将设计一种名为适体的DNA链，这种适体具有3D结构，可以与单一类型的嗅觉受体特异结合，并诱导信号转导。这些基于DNA的“人造气味”将被贴上一种纳米颗粒的标签，这种纳米颗粒会在外部电磁场的作用下改变其构象。该产品将是人工气味，可以在体内进行外部切换。松岛实验室将使用表达嗅觉受体的组织培养细胞来验证这些可切换的纳米机器人气味的功能和选择性。然后，索贝尔实验室将把这些人造气味应用到人类嗅觉系统中，并在开启和关闭人造气味后测量感知和神经活动。这种三级方法将允许闭合从感受器到知觉的环路，并可能以这种方式回答仍然是嗅觉中的一个基本问题。

The sense of small (olfaction) holds in it a major mystery: No scientist or perfumer can look at the structure of a novel molecule and predict its odor or molecular structure. This project aims to develop molecules that bind to individual olfactory receptors in the nose and thereby help solve the code by which odors result in odor perception. The proposed approach has broad implications and applications: It may pave the path towards the introduction of odor into everyday devices. The idea of odor-emitting televisions, computer game boxes, cell-phones, etc, has existed for some time. However, this goal remains unattained, mostly for "simple" technical reasons: Even if one successfully generates an odor-emitting device, what does one then do with the emitted odor? For example, a car-racing computer game may emit the smell of burning rubber tires, but how does one then evacuate the smell of burning rubber from the room? Moreover, given that odors linger, how can one rapidly switch from one odor to the next? The technology proposed here may solve these problems because it will entail particles that are odorless, yet take on a given odor as a function of rapidly-switchable externally applied fields. If successful, the proposed mechanism will drive a revolution of odor devices. Further, the "switchable chemical" approach will be extendable to other receptors in the brain, and can be applied towards asking basic questions concerning emotion, sensorimotor-coordination, memory and learning, as well as developing potential novel therapies for diseases associated with receptor signaling failure. To develop a path towards solving the combinatorial code of olfaction, the Bachelet lab will design DNA strands called aptamers that assume a 3D structure that will specifically bind to a single type of olfactory receptor and induce signal transduction. These DNA-based "artificial odorants" will be tagged with a nanoparticle that changes its conformation in response to an external electromagnetic field. The product will be artificial odorants that are externally switchable in vivo. The Matsunami lab will use tissue culture cells expressing olfactory receptors to validate the function and selectivity of these switchable nano-robot odorants. The Sobel lab will then apply these artificial odorants to the human olfactory system, and measure perception and neural activity following switching the artificial odor on and off. This three-level approach will allow closure of the loop from receptor to perception, and potentially answer in this way what remains a fundamental question in olfaction.