Live imaging and genetic dissection of immunothrombosis in Drosophila

果蝇免疫血栓的实时成像和基因解剖

• 批准号: MR/W017407/1
• 负责人: Brian Stramer
• 金额: $ 58.71万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW017407%2F1
• 关键词: Live; imaging; genetic; dissection; immunothrombosis

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.

受伤后，血凝块立即形成，以止血和阻止感染。随后，炎症细胞被募集到伤口以去除组织碎片并防止感染，最后修复受损组织。控制这些伤口愈合反应的机制对于生存至关重要，并且几乎发生在所有动物中。然而，现在的挑战是了解这些看似不同的组织修复过程是如何协调的，因为很明显凝块形成不能与伤口反应的其他方面分开。（果蝇），在增强我们对伤口愈合和炎症的理解方面，以确定凝血是如何调节的，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。我们将第一次在果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伤口修复的其他方面。我们将首先利用我们获得活体果蝇中凝块形成、炎症和伤口愈合的电影的能力，检查整个组织修复过程中凝血反应的动力学。随后，我们将利用我们的能力，快速分析果蝇中特定基因的功能，以确定控制凝块形成的机制，包括从受损组织或炎症反应中发出的已知信号。最后，我们将测试凝血功能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。由于果蝇中的许多伤口反应信号与高等生物相似，因此这里确定的机制可能提供新的途径，使我们能够干预和调节人类的炎症和组织修复。