MOLECULAR GENETIC ANALYSIS OF WOUND HEALING--DROSOPHILA

导致组织或组织完整性丧失的创伤构成伤口，并启动伤口愈合或修复过程。 该过程的关键特征包括实现即时组织稳态，排斥微生物，并最终恢复正常组织生理学。人类的创伤和创伤愈合具有相当大的生物学和社会意义。 伤口发生意外，可以造成愤怒，或发生在手术期间，有益的医疗原因。 我们提出的工作的最终目标是了解上皮对伤口反应的基本生物学，长期目标是有助于设计旨在加速愈合或防止过度瘢痕形成的干预策略。 已经开发了许多脊椎动物，特别是哺乳动物，动物模型系统来研究创伤和伤口愈合。 因此，负责适当伤口愈合的分子参与者已经开始被确定。 最近，基因敲除和转基因小鼠技术已被应用于伤口愈合的研究。 然而，哺乳动物模型系统只能在经过仔细的伦理考虑后才能用于创伤研究，自然是耗时且非常昂贵的。 此外，正向基因筛选基本上是不切实际的。 在这里，我们建议追求的分子/遗传策略，是唯一可用的果蝇，调查生物学的创伤和伤口愈合。 最近，我们使用机械和激光方法消融果蝇胚胎中的组织，并发现这种消融之后是快速和强大的愈合。 此外，我们发现，愈合是完全抑制在肌球蛋白重链的结构基因缺陷的纯合子胚胎。 我们建议在果蝇的创伤和伤口愈合的特点，测试的作用，候选位点的创伤和伤口愈合的过程中，并进行正向遗传筛选，以恢复位点，不能正确愈合。 这些研究将直接解决上皮伤口愈合的那些方面，这些方面在5亿至10亿年的进化中保持不变，将昆虫与哺乳动物分开。 他们一起承诺将果蝇遗传学和分子遗传学的强大工具用于解决这一重要的生物学问题。

Trauma that results in loss of tissue or tissue integrity constitutes a wound, and initiates a wound healing or repair process. Key features of that process include achieving immediate tissue homeostasis, repelling microorganisms and ultimately, the restoration of normal tissue physiology. Wounding and wound healing in humans is of considerable biological and social significance. Wounds occur by accident, can be inflicted in anger, or occur during surgery, for beneficial medical reasons. The ultimate goal of the work we propose is to understand the basic biology of epithelial response to wounds with the long range goal of contributing to the design of intervention strategies designed to speed healing or prevent excessive scarring. A number of vertebrate, and especially mammalian, animal model systems have been developed to study wounding and wound healing. As a consequence, the molecular players responsible for proper wound healing have begun to be identified. Recently, knockout and transgenic mouse technologies have been applied to the study of wound healing. Nevertheless, mammalian model systems can be used in wounding studies only after careful ethical consideration, are naturally time consuming and are very expensive. Moreover, forward genetic screens are essentially impractical. Here, we propose to pursue molecular/genetic strategies that are uniquely available in Drosophila to investigate the biology of wounding and wound healing. Recently we used mechanical and laser methods to ablate tissue in Drosophila embryos and found that such ablations are followed by rapid and robust healing. Moreover, we found that healing was completely inhibited in embryos homozygous for defects in the structural gene for myosin heavy chain. We propose to characterize wounding and wound healing in Drosophila, test the role of candidate loci in the process of wounding and wound healing, and perform forward genetic screens to recover loci that fail to heal properly. These studies will address directly those aspects of epithelial wound healing that are conserved over the 0.5 to 1 billion years of evolution that separate insects from mammals. Together, they promise to bring the powerful tools of Drosophila genetics and molecular genetics to bear on this important biological problem.