Molecular mechanism of touch sensitivity in the Schnauzenorgan of the Elephant Nose Fish

象鼻鱼雪纳森器官触觉敏感性的分子机制

• 批准号: 2114084
• 负责人: Sviatoslav Bagriantsev
• 金额: $ 95万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2114084&HistoricalAwards=false
• 关键词: Molecular; mechanism; touch; sensitivity; Schnauzenorgan

This research focuses on the sense of touch – a fundamental physiological capacity present in all animals, including humans, which endows them with the ability to sense the physical world through the skin. The sense of touch is essential for navigation in the environment, for handling tools, manipulating objects, detecting the texture of food, for sensing a mother’s caring touch or the bite of a predator. Even though the sense of touch is important for every aspect of an animal’s existence, it remains one of the least well understood senses. Indeed, we know very little about how touch is detected, and how this ability changes in different species during evolution. This project aims to fill the gap in our knowledge about the sense of touch by studying Elephant Nose Fish (Gnathonemus petersii). G. petersii is a tactile specialist animal who uses its flexible chin appendage, called the Schnauzenorgan, in a manner similar to a finger in order to find food in the bed of murky rivers. The fascinating ability of G. petersii to find food by touch rather than through vision or smell lends a unique opportunity to study this sense from the perspective of a tactile champion. This project will obtain mechanistic insights into the process of touch detection by sensory neurons of the peripheral nervous system of vertebrates. To achieve broader impact, results from this research will be disseminated through an extracurricular outreach program. By combining in-person lectures and experiments with online classes, this outreach program will disseminate scientific knowledge in the area of physiology among students of different ages, with an emphasis on the ethnic and socioeconomic groups traditionally underrepresented among scientists. The scientific and outreach components of this project will provide fundamental training for graduate students to foster their development as researchers and educators.This project will investigate how G. petersii achieves mechanosensory specialization at cellular and molecular levels. The Schnauzenorgan of G. petersii is innervated by myelinated trigeminal touch receptors, which terminate in the skin as bare nerve endings, without forming a complex with corpuscular structures. The goal of this project is to perform functional and histological investigation of the novel type of mechanoreceptors from the Schnauzenorgan of G. petersii, and identify the molecular mechanism of its touch sensitivity. The project will test whether the trigeminal ganglia of G. petersii contains an expanded population of mechanoreceptors, investigate whether mechanoreceptors innervating the Schnauzenorgan of G. petersii have augmented ability to sense touch, and reveal molecules that convert touch into excitation. To achieve this, the project will utilize a multidisciplinary approach, combining electrophysiology, histology and bioinformatics. Results from this proposal will be essential for understanding molecular evolution of mechanosensitivity in vertebrates.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项研究的重点是触觉-一个基本的生理能力存在于所有动物，包括人类，这赋予他们通过皮肤感知物理世界的能力。触觉对于在环境中导航、处理工具、操纵物体、检测食物的质地、感知母亲的关怀触摸或捕食者的叮咬是必不可少的。尽管触觉对动物生存的各个方面都很重要，但它仍然是人们最不了解的感官之一。事实上，我们对触摸是如何被检测到的，以及这种能力在不同物种的进化过程中是如何变化的知之甚少。本计画的目的是借由研究象鼻鱼（Gnathonemus petersii）来填补我们对触觉认知的差距。G. Petersii是一种触觉专家动物，它使用其灵活的下巴附属物，称为Schnauzenorgan，以类似于手指的方式在浑浊的河床中寻找食物。G.彼得西通过触摸而不是通过视觉或嗅觉来寻找食物，这为从触觉冠军的角度研究这种感觉提供了一个独特的机会。本项目将从机理上深入了解脊椎动物外周神经系统的感觉神经元对触摸的检测过程。为了实现更广泛的影响，这项研究的结果将通过课外推广计划传播。通过将面对面的讲座和实验与在线课程相结合，该推广计划将在不同年龄的学生中传播生理学领域的科学知识，重点是传统上在科学家中代表性不足的种族和社会经济群体。该项目的科学和推广部分将为研究生提供基本的培训，以促进他们作为研究人员和教育工作者的发展。Petersii在细胞和分子水平上实现机械感觉特化。G. Schnauzenorgan Petersii由有髓鞘的三叉神经触觉感受器支配，其在皮肤中终止为裸露的神经末梢，而不与微粒结构形成复合体。本研究的目的是对来自于G. petersii，并确定其触摸敏感性的分子机制。本项目将测试G. petersii含有大量的机械感受器，研究是否有机械感受器支配G. Petersii有增强的触觉感知能力，并揭示了将触觉转化为兴奋的分子。为了实现这一目标，该项目将利用多学科方法，结合电生理学，组织学和生物信息学。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的知识价值和更广泛的影响审查标准进行评估来支持。

项目成果

Human TRPV1 structure and inhibition by the analgesic SB-366791.

• DOI: 10.1038/s41467-023-38162-9
• 发表时间: 2023-04-28
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Neuberger, Arthur;Oda, Mai;Nikolaev, Yury A.;Nadezhdin, Kirill D.;Gracheva, Elena O.;Bagriantsev, Sviatoslav N.;Sobolevsky, Alexander I.
• 通讯作者: Sobolevsky, Alexander I.

Mechanotransduction events at the physiological site of touch detection.

• DOI: 10.7554/elife.84179
• 发表时间: 2023-01-06
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Ziolkowski, Luke H.;Gracheva, Elena O.;Bagriantsev, Sviatoslav N.
• 通讯作者: Bagriantsev, Sviatoslav N.