Molecular and Cellular Mechanisms of Wound Repair

项目概要/摘要 人体的大多数细胞在发育过程中都暴露在广泛的生理和环境压力下， 它们的正常日常功能，可能导致细胞质膜和底层的破坏， 皮质细胞骨架细胞修复一般日常磨损损伤的能力，以及 由于创伤或从感染到疾病/癌症的病理状况引起的， 对他们的生存至关重要。这项建议的总体目标是了解细胞如何科普这些 膜和皮层细胞骨架破坏。我们已经开发了一个单细胞修复模型， 合胞体果蝇胚胎被证明是体内细胞研究的极好模型， 由于其对活体成像的顺从性及其在其他细胞中不可用的遗传易处理性， 创伤修复模型我们的长期目标是描绘分子和细胞机制 控制细胞创伤修复这项提案的具体目标是：1）确定细胞是如何被撕裂的， 质膜迅速重新密封和重塑; 2）以确定最初的均匀修复 信号导致修复因子精确地时空募集到伤口部位;和3） 确定肌动蛋白环附着在上覆质膜上的性质和调节 促进细胞伤口闭合。我们的研究结果应该跨门推断，补充工作是 在其他实验系统中完成，为细胞修复的关键事件提供了新的见解， 在其他领域的工作，有助于了解相关的基本细胞和 发展过程。虽然性质基本，我们的研究也将是重要的医疗 相关性，因为了解控制细胞创伤修复的事件对于开发 治疗细胞损伤（或增强现有治疗的有效性）或 诸如再生医学的学科，其中基于细胞的构建体被植入以重建 组织中

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.