Drosophila melanogaster as a model for mammalian inflammatory response

Study of blood in the context of mammalian inflammatory response has been hindered by the difficulty to observe and manipulate the response in vivo. However, Drosophila melanogaster may serve as a more effective and efficient model for the mammalian inflammatory pathway because of the multitude of Drosophila genes conserved in humans, vast knowledge of the system, and its convenience as an easily maintained organism. In the case of injury, Drosophila demonstrates an injury response, through the Toll/Dorsal-Dif pathway, very similar to that of the vertebrate Toll Like Receptor/NF-κB pathway. The goal of this study is to identify how blood cell function and hematopoietic development are influenced by injury in Drosophila. To understand the analogous hematopoietic injury response, we are studying the injury induced Toll activation in the hemolymph or blood, in Dorsal-Dif regulated transgenic reporter lines that express fluorescent markers (EGFP and RFP) which provide visualization of the blood system. These transgenic lines are able to monitor blood because they have been created with four or twelve copies of the Dorsal binding sequence that drives the production of GFP or RFP. The lines have been characterized, injured and uninjured, through analysis of whole larvae, blood, and larval lymph glands, which produces blood, via fluorescent microscopy. Once thoroughly analyzed, the optimal fluorescent reporter lines will be used for an in vivo genetic screen to find novel activators of upstream components of the Toll pathway.