Molecular and Cellular Mechanisms of Wound Repair

项目摘要/摘要 身体的大多数细胞都暴露在各种各样的生理和环境压力下 它们的正常日常功能会导致细胞质膜的破坏和潜在的 皮质细胞骨架。细胞修复日常磨损损伤的能力也是如此 由于创伤或从感染到疾病/癌症等病理条件引起的疾病，是 对它们的生存至关重要。这项建议的总体目标是了解细胞如何应对这些 细胞膜和皮质细胞骨架的破坏。我们已经开发了一个单细胞修复模型，使用 合胞果蝇胚胎被证明是体内细胞研究的极好模型 修复是由于它对活体成像的适应性以及它在其他细胞中所不具备的遗传易感性 伤口修复模型。我们的长期目标是描绘出分子和细胞机制 管理细胞创伤修复。这项建议的具体目标是1)确定细胞如何撕裂 质膜被快速重新密封和重塑；2)确定最初如何均匀修复 信号导致修复因子在时空上精确地募集到伤口部位；以及3) 确定肌动蛋白环附着于上一层质膜的性质和调节 促进细胞伤口的愈合。我们的发现应该跨门而外推，补充工作 在其他实验系统中完成，提供了对细胞修复的关键事件和影响的新见解 在其他领域工作，帮助理解相关的基本细胞和 发育过程。虽然我们的研究是基础性的，但也将具有重要的医学意义 相关性，因为了解控制细胞创伤修复的事件将对发展 治疗细胞损伤(或增强现有损伤的有效性)或 一些学科，如再生医学，将基于细胞的结构植入以重建 纸巾。

PROJECT SUMMARY/ABSTRACT Most cells of the body are exposed to a wide range of physiological and environmental stresses during their normal daily functions that can lead to disruption of the cell’s plasma membrane and underlying cortical cytoskeleton. The capacity of cells to repair general day-to-day wear-and-tear injuries, as well as ones resulting from trauma or pathological conditions ranging from infection to diseases/cancer, is essential for their survival. The general aim of this proposal is to understand how cells cope with these membrane and cortical cytoskeleton disruptions. We have developed a single cell repair model using the syncytial Drosophila embryo that is proving to be a superb model for the in vivo study of cellular repair owing to its amenability for live imaging and its genetic tractability that is unavailable in other cell wound repair models. Our long-term goal is to delineate the molecular and cellular mechanisms governing cell wound repair. The specific aims of this proposal are 1) to determine how a cell’s torn plasma membrane is rapidly re-sealed and remodeled; 2) to determine how the initial uniform repair signal results in the precise spatio-temporal recruitment of repair factors to the wound site; and 3) to determine the nature and regulation of the actin ring attachment to the overlying plasma membrane facilitating cell wound closure. Our findings should extrapolate across phyla, complement work being done in other experimental systems, provide new insight into key events of cellular repair, and impact work in other fields by contributing to the understanding of related fundamental cellular and developmental processes. While fundamental in nature, our studies will also be of significant medical relevance, as understanding the events controlling cell wound repair will be important for developing new strategies for treating cellular damage (or for augmenting the effectiveness of existing ones) or for disciplines such as regenerative medicine where cell based constructs are implanted to reconstruct tissues.