Cell volume regulation - the search for a volume sensor

动物细胞体积是决定多种细胞功能的重要因素，包括细胞生长和死亡、离子转运和细胞代谢。细胞体积的变化在许多病理条件下，如脑损伤、糖尿病并发症和其他疾病。细胞体积是通过激活膜转运蛋白和代谢过程来严格调节的，这些过程提供了细胞内渗透压的净损失或净增加。然而，在我们对细胞如何检测体积扰动的知识中存在着一个重大的差距。细胞体积传感器的识别仍然是细胞体积调节领域中最重要的挑战，而这一研究领域的进展主要是由于缺乏合适的方法来监测单个活细胞的体积变化。我们的实验室最近发明了一种新的方法，可以对单个活细胞进行三维成像。在提出的研究方案中，我们建议进一步改进我们的单细胞体积监测系统原型，并将其应用于阐明细胞体积传感机制(S)。我们还将应用这项技术来研究被包裹用于治疗输送的细胞的体积调节。这项研究计划既保证了单细胞成像技术的创新，也保证了我们对细胞如何感知其体积变化的理解的显著进步。对这些机制的探索对于全面了解正常和病理条件下广泛的相关细胞过程是必不可少的。这项研究的性质涵盖细胞生理学、细胞生物学、显微镜成像、暗室设计和软件开发，将使我们能够以多学科的方式更好地培训学生。

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.