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

BRAIN EAGER：使用纳米机器人可切换气味剂解决嗅觉密码

• 批准号: 1450993
• 负责人: Hiroaki Matsunami
• 金额: $ 30万
• 依托单位: Duke University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1450993&HistoricalAwards=false
• 关键词: BRAIN; EAGER; Solving; Code; Olfaction

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.

小的感觉（嗅觉）蕴藏着一个重大谜团：没有科学家或调香师能够观察新分子的结构并预测其气味或分子结构。该项目旨在开发与鼻子中个体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。所提出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、电脑游戏盒、手机等的想法已经存在了一段时间。然而，这一目标仍未实现，主要是出于“简单”的技术原因：即使成功地制造了一种散发气味的装置，那么人们会如何处理散发的气味呢？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，但如何从房间中消除橡胶燃烧的气味呢？此外，鉴于气味挥之不去，人们如何能够快速从一种气味切换到另一种气味呢？这里提出的技术可以解决这些问题，因为它将需要无味的颗粒，但会根据快速切换的外部施加场而呈现给定的气味。如果成功，所提出的机制将推动气味设备的一场革命。 此外，“可切换化学”方法将扩展到大脑中的其他受体，并可应用于询问有关情绪、感觉运动协调、记忆和学习的基本问题，以及开发针对与受体信号传导失败相关的疾病的潜在新疗法。为了开发一条解决嗅觉组合密码的途径，Bachelet 实验室将设计称为适体的 DNA 链，其采用 3D 结构，可特异性结合单一类型的嗅觉受体并诱导信号转导。这些基于 DNA 的“人造气味剂”将被贴上纳米颗粒的标签，纳米颗粒会根据外部电磁场而改变其构象。该产品将是可在体内外部转换的人造气味剂。 Matsunami 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纳米机器人气味剂的功能和选择性。然后，索贝尔实验室将把这些人造气味剂应用于人类嗅觉系统，并在打开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关闭从受体到感知的循环，并可能以这种方式回答嗅觉中仍然存在的基本问题。