Live imaging and genetic dissection of immunothrombosis in Drosophila

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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.