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

嗅觉是一个很大的谜团：没有科学家或调香师可以通过观察一种新分子的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受体结合的分子，从而帮助解决气味导致气味感知的代码。提出的方法具有广泛的含义和应用：它可能为将气味引入日常设备铺平道路。散发气味的电视、电脑游戏盒、手机等的想法已经存在了一段时间。然而，这个目标仍然没有实现，主要是由于“简单”的技术原因：即使成功地制造了一个气味发射装置，那么人们对发出的气味做什么呢？例如，一款赛车电脑游戏可能会散发出橡胶轮胎燃烧的气味，但人们如何将燃烧的橡胶气味从房间中疏散出去呢？此外，考虑到气味会持续存在，人们如何快速地从一种气味切换到另一种气味呢？这里提出的技术可能会解决这些问题，因为它将需要无气味的颗粒，但具有给定的气味作为快速切换的外部应用领域的功能。如果成功，该机制将推动一场气味装置的革命。此外，“可转换化学”方法将扩展到大脑中的其他受体，并可应用于询问有关情感，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传导失败相关的疾病的潜在新疗法。为了找到解决嗅觉组合密码的途径，巴切莱特实验室将设计一种被称为适体的DNA链，这种DNA链具有3D结构，可以特异性地与一种嗅觉受体结合，并诱导信号转导。这些基于dna的“人造气味剂”将被贴上纳米粒子的标签，纳米粒子可以根据外部电磁场改变其构象。该产品将是在体内外部可切换的人造气味剂。Matsunami实验室将使用组织培养细胞表达嗅觉受体来验证这些可切换的纳米机器人嗅觉剂的功能和选择性。然后，索贝尔实验室将把这些人工气味剂应用于人类嗅觉系统，并在打开和关闭人工气味后测量感知和神经活动。这种三层次的方法将关闭从受体到感知的回路，并有可能以这种方式回答嗅觉中仍然存在的一个基本问题。

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.