细胞迁移是器官形成与发育的基础，参与胚胎发生、伤口愈合、免疫反应以及肿瘤转移等过程，细胞膜-微丝骨架动态重排在这过程中起着关键性调节作用。Supervillin(SVIL)是一个重要的膜-微丝骨架结合蛋白，它与微丝，以及MyosinII、Cortactin等微丝调节蛋白相互作用，调控细胞迁移与侵袭；我们最近发现其在肿瘤组织与细胞中特异高表达，但涉及的相互作用网络、信号转导分子机理、生化途径不甚明了。我们拟采用先进的生物光子学、细胞生物学、生物物理学及实验动物学等手段，对SVIL在微丝介导的膜-细胞微丝骨架动力学调控中的功能特性进行精确解析，揭示SVIL相互作用网络、信号传导、磷酸化修饰对其功能调节效应，通过体内外系统阐明SVIL介导的微丝细胞骨架重排在细胞迁移与侵袭过程中的作用机制。进而探索SVIL功能异常引起的病理机制，为相关疾病临床治疗与研究提供理论基础。

Cell migration is a fundamental process in the development and the maintenance for multi-cellular organisms, including embryonic development, wound healing, immune response and tumor metastasis. The remodeling of membrane-actin cytoskeleton plays a central role during this process. Supervillin(SVIL) is a very important membrane-cytoskeleton binding protein, it directly interacts with F-actin and actin-binding proteins such as Myosin II, Cortactin to regulate cell migration and cell invasion. We recently found SVIL is specially over-expressed in tumor tissues and tumor cell lines. However, it is still very limited to the understanding of the function of SVIL in its interacting networks, signaling transduction and biochemical pathway. We propose to combine bio-photonics, cell biology, biophysics and experimental animal model to dissect the properties of SVIL in the actin-based membrane-cytoskeletal dynamics. The aim is to demonstrate molecular mechanism of SVIL-mediated remodeling of membrane - actin cytoskeleton during cell migration and cell invasion. We also want to identify more SVIL interaction partners and reveal the regulatory effect by the interaction network, the signaling pathway and post-modification of phosphorylation. Furthermore, we try to explore the pathological mechanism of the disease resulted from the abnormal SVIL function, which will provide theoretical basis for intervention of related diseases and lay out a solid foundation for future clinical research.