Tootle Lab

The Tootle Lab’s long-term objective is to understand how particular prostaglandin signaling events result in specific biological outcomes. Prostaglandins are locally acting, transient hormones that mediate a wide variety of biological activities, from female reproduction to cancer development and progression. Prostaglandins are synthesized at their sites of action by cyclooxygenase (COX) enzymes, the targets of Aspirin and Advil. As prostaglandin signaling is transient and locally acting, to determine the molecular mechanism of prostaglandin action a cell-cell signaling model is needed. Drosophila is an excellent system to use, as Drosophila genetics has been routinely employed to identify and characterize signaling cascades at single cell resolutions.

Previously, we developed Drosophila oogenesis as a new and powerful model for studying prostaglandin signaling. Using both pharmacology and genetics, we discovered that prostaglandins mediate Drosophila follicle development, identified the Drosophila COX1 enzyme, Pxt, and revealed that genetic perturbation of prostaglandin signaling can be used to exam the function of prostaglandins. This research reveals that prostaglandin signaling modulates actin/membrane dynamics, cell migration, stem cell activity, and the timing of gene expression during Drosophila follicle development.

The lab is currently pursuing how prostaglandin signaling regulates actin dynamics during follicle development. Both pharmacology and genetics reveal that prostaglandin signaling is required for nurse cell dumping, a process in which the germline derived nurse cells push all of their cytoplasmic contents into the oocyte. In mutants with no prostaglandin signaling the actin structures required for nurse cell dumping are substantially reduced and often completely eliminated. By using a multifaceted experimental approach that combines Drosophila genetics, cell biology, live imaging, and biochemistry to my lab will be able to determine where the prostaglandin signal is coming from, which prostaglandins are involved, whether this is by the canonical signaling pathway, how prostaglandin signaling interacts with known actin regulators, and the downstream changes in gene expression during nurse cell dumping. The results from these studies are likely to provide general insight into how prostaglandins regulate the cytoskeleton at a cellular level. Such mechanisms of prostaglandin action are likely to be reutilized throughout development, including mediating the cytoskeletal changes that occur during cancer progression and metastasis.