Cell volume regulation - the search for a volume sensor

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Animal cell volume is an important factor that defines various cellular functions, including cell growth and death, ion transport, and cell metabolism. Cell volume changes in many pathological conditions, such as brain injuries, diabetic complications and other disorders. Cell volume is tightly regulated via activation of membrane transporters and metabolic processes that provide a net loss or gain of intracellular osmolytes. A major gap, however, exists in our knowledge of how cells detect volume perturbations. Identification of the cell volume sensor remains the most significant challenge in the field of cell volume regulation, and progress in this research area is mainly hindered by the lack of appropriate methods to monitor volume changes of single, living cells. Our laboratory has recently invented a novel method which allows imaging single, live cells in 3 dimensions. In the proposed research program we propose to further improve our prototype single-cell volume-monitoring system and apply it to elucidate cell volume-sensing mechanism(s). We will also apply this technique to study volume regulation in cells encapsulated for therapeutic delivery. This research program promises both innovation in single-cell imaging techniques and notable advancement of our understanding of how cells sense changes in their volume. Exploration of these mechanisms is essential for full understanding of a broad range of related cellular processes in normal and pathological conditions. The nature of this research encompassing cell physiology, cell biology, microscopy imaging, chamber design and software development will allow us to  train students in a multidisciplinary manner.