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

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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.