Live imaging and genetic dissection of immunothrombosis in Drosophila

受伤后，立即形成血块来止血和阻止感染。随后，炎症细胞被招募到伤口，清除组织碎片，防止感染，最终修复受损组织。控制这些伤口愈合反应的机制对生存至关重要，并且几乎在所有动物中都存在。然而，现在的挑战是理解这些看似不同的组织修复过程是如何协调的，因为很明显，血块的形成不能与伤口反应的其他方面分开。在这里，我们将利用一种简单的生物，果蝇（果蝇），它在增强我们对伤口愈合和炎症的理解方面一直是一个强大的力量，来确定如何调节凝血并随后控制组织修复的其他方面。近年来，我们和其他人已经揭示了这些过程背后的机制，凝血、炎症和组织修复，可以在果蝇的帮助下阐明。这是第一次，我们将在苍蝇中同时全面检查所有这些过程，以检查凝血过程如何控制或受其他方面的控制伤口修复。我们将首先利用我们在活果蝇中获得凝块形成，炎症和伤口愈合的电影的能力来检查组织修复过程中凝固反应的动力学。随后，我们将利用我们快速分析果蝇特定基因功能的能力来确定控制凝块形成的机制，包括来自受损组织或炎症反应的已知信号。最后，我们将测试凝血的丧失如何影响炎症细胞的募集和组织愈合。我们的目标是全面了解凝血级联是如何与组织修复过程的其他方面交织在一起的。由于果蝇的许多伤口反应信号与高等生物相似，因此本文确定的机制可能为我们干预和调节人类的炎症和组织修复提供新的途径。

Upon injury, a blood clot is immediately formed to stop bleeding and block infection. Subsequently, inflammatory cells are recruited to the wound to remove tissue debris and prevent infection, and finally the damaged tissue is repaired. The mechanisms controlling these wound healing responses are critical for survival and occur in nearly all animals. However, the challenge now is to understand how these seemingly disparate tissue repair processes are coordinated as it has become evident that clot formation cannot be disentangled from other aspects of the wound response.Here we will exploit a simple organism, Drosophila melanogaster (fruit fly), which has been a powerhouse in terms of enhancing our understanding of wound healing and inflammation, to determine how clotting is regulated and subsequently controlling other aspects of tissue repair. In recent years we and others have revealed that the mechanisms behind each of these processes, clotting, inflammation, and tissue repair, can be elucidated with the help of fruit flies. For the first time we will holistically examine all of these processes simultaneously in the fly in order to examine how the process of coagulation is controlling - or controlled by - other aspects wound repair.We will first exploit our ability to acquire movies of clot formation, inflammation, and wound healing in the living fruit fly to examine the dynamics of the coagulatory response throughout tissue repair. We will subsequently take advantage of our ability to rapidly analyse the function of specific genes in the fruit fly to determine the mechanisms controlling clot formation, including known signals emanating from damaged tissues or the inflammatory response. Finally we will test how the loss of clotting affects inflammatory cell recruitment and tissue healing. Our goal is to holistically understand how the coagulatory cascade is intertwined with other aspects of the tissue repair process. As many of the wound response signals in the fruit fly are similar to higher organisms, the mechanisms identified here are likely to provide novel avenues that may allow us to intervene and modulate inflammation and tissue repair in humans.