ERI: The Role of a Novel Mechanosensitive Channel Modulator in Inflammation

该工程研究启动奖(ERI)将支持细胞如何检测机械载荷(机械转导)的研究。机械转导将机械负荷转化为生物反应。机械触发的细胞表面开口(机械敏感通道)是最著名的细胞力传感系统。它们对触觉和听觉很重要，对许多人类疾病都有效果。该领域的一个研究挑战是发现可以选择性地触发机械敏感离子通道的分子。一些分子触发这些通道是已知的，但它们如何发挥作用尚不清楚。了解这些人造分子的功能可以在许多方面有所帮助，包括接受它们作为治疗人类疾病的药物。该奖项支持的研究目的是发现一种新的机械敏感通道调节剂的作用机制。这项研究的结果可以用来理解与经络相关的疾病，从而为社会带来好处。多学科研究活动将使多个代表性不足的群体参与研究，从而获得进一步的好处。Piezo(Piezo1和Piezo2)机械敏感通道是非选择性阳离子机械敏感通道，在听觉、触觉和炎症等多种生理过程中发挥着重要作用。该项目的目标是研究新的Piezo1调节剂在炎症中的作用。这一目标将通过以下方式实现：i)鉴定和鉴定一种新型的Piezo1激活剂，这将为未来的机械敏感通道研究提供基础平台；ii)开发对研究机械敏感通道的生物力学特性至关重要的电容钳技术，并为研究离子通道提供电生理平台；iii)建立用于炎症研究的培养星形胶质细胞模型；以及iv)提供炎症的潜在机制。该项目的主要成果将是发现一种通过靶向Piezo1来治疗炎症的新的治疗策略，这将促进神经科学、发育生物学和免疫学的研究和教育。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This Engineering Research Initiation (ERI) award will support research on how cells detect mechanical loading (mechanotransduction). Mechanotransduction converts mechanical load into a biological response. Mechanically triggered openings in the cell surface (mechanosensitive channels) are the best-known cellular force-sensing systems. They are important for the senses of touch and hearing and have effects in many human diseases. A research challenge for the field is discovering molecules that can selectively trigger a mechanosensitive ion channel. Some molecules are known for triggering these channels but how they function in not known. Knowing how these artificial molecules function could help in many ways, including acceptance of them as a drug for treating diseases in people. The research supported by this award has the goal of discovering the mechanism of action for a new mechanosensitive channel modulator. Results from this research could be used to understand channel-associated diseases, producing benefits for society. Further benefits will be achieved through the multi-disciplinary research activities that will engage multiple underrepresented groups in research. Piezo (Piezo1 and Piezo2) mechanosensitive channels are non-selective cation mechanosensitive channels, playing important roles in diverse physiological processes, including hearing, touching, and inflammation. The goal of this project is to investigate the roles of new Piezo1 modulator on inflammation. This aim will be achieved by: i) identifying and characterize a novel Piezo1 activator, which will generate a fundamental platform for future mechanosensitive channel studies; ii) development of a capacitance clamp technique that is critical to study the biomechanical properties of mechanosensitive channels and provides an electrophysiological platform for studying ion channels; iii) development of a cultured astrocyte cell model for inflammation studies; and iv) providing the underlying mechanism of inflammation. The major outcome of this project will be the discovery of a novel therapeutic strategy for treating inflammation by targeting Piezo1 that will promote research and education in neuroscience, developmental biology, and immunology.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.