New approaches to identify molecular mechanisms of touch and pain in mammals

描述（由申请人提供） 翻译后摘要：机械转导是机械能转换成电信号或生化信号的过程。在哺乳动物中，机械传导是各种感觉的基础，包括听觉、触觉和本体感受。基本的生理过程，如血压调节和膀胱功能，也依赖于正常的稳态功能的机械转导。尽管其广泛的重要性，很少有人知道的哺乳动物的机械转导的分子机制。不同的细胞是否使用相同的转导分子，这些分子被细胞环境所修饰？或者，是否有多个机械传感器专门用于感测不同类型的机械刺激？他的目标是确定哺乳动物躯体感觉神经元中介导机械传导的分子，这些细胞传达我们的触觉和疼痛感。虽然已经确定了一些候选mechanotensors，这些候选人的异源表达并没有产生功能mechanosensitive通道，也没有基因敲除研究证实的作用，这些候选人在哺乳动物躯体感觉mechanotensortransduction。我的实验室将采用几种无偏倚的方法来鉴定新的候选机械转导分子。该提案的具体目标是：（1）识别机械传导机制的组成部分和（2）检查候选分子对体内躯体感觉的贡献。这些研究将提供新的见解分子力传感器，哺乳动物mechanotransduction的基础。 公共卫生相关性：虽然疼痛令人不快，但它警告我们不要受到环境中的有害刺激，并唤起保护性反射。但疼痛也可能是一种慢性的、使人衰弱的痛苦，不再起保护作用。慢性疼痛不仅发生在创伤引起的炎症和组织损伤之后，而且还由许多疾病引起;疼痛是癌症、艾滋病和糖尿病患者的主要主诉。了解引起急性和慢性疼痛的机制可能会导致急需的新药物和疗法的发展，以减轻疼痛。

DESCRIPTION (Provided by the applicant) Abstract: Mechanotransduction is the process by which mechanical energy is converted into electrical or biochemical signals. In mammals, mechanotransduction underlies a variety of senses, including hearing, touch and proprioception. Basic physiological processes, such as blood-pressure regulation and bladder function, also rely on mechanotransduction for normal homeostatic function. Despite its widespread importance, little is known about the molecular mechanisms underlying mechanotransduction in mammals. Do different cells use the same transduction molecules that are modified by cellular context? Or, are there multiple mechanotransducers that specialize in sensing different types of mechanical stimuli? The goal of his proposal is to identify molecules that mediate mechanotransduction in mammalian somatosensory neurons, the cells that convey our sense of touch and pain. While some candidate mechanotransducers have been identified, heterologous expression of these candidates has not yielded functional mechanosensitive channels, nor have gene knockout studies confirmed a role for any of these candidates in mammalian somatosensory mechanotransduction. My laboratory will undertake several unbiased approaches to identify new candidate mechanotransduction molecules. The specific aims of this proposal are to: (1) Identify components of the mechanotransduction machinery and (2) Examine the contribution of candidate molecules to somatosensation in vivo. These studies will provide novel insight into the molecular force transducers that underlie mammalian mechanotransduction. Public Health Relevance: Though unpleasant, pain warns us against harmful stimuli in the environment and evokes protective reflexes. But pain can also be a chronic, debilitating affliction that no longer serves a protective purpose. Chronic pain not only occurs after trauma-induced inflammation and tissue injury, but also results from many diseases; pain is the major complaint of patients suffering from cancer, AIDS, and diabetes. Understanding the mechanisms that evoke acute and chronic pain may lead to the development of much needed, new drugs and therapies to alleviate pain.