Tina Tootle, PhD
Uncovering the mechanisms of prostaglandin action
Prostaglandins (PGs) are locally acting, transient hormones that mediate a wide variety of biological activities, from female reproduction to cancer development and progression. PGs are synthesized at their sites of action by cyclooxygenase enzymes, the targets of Aspirin and Advil. As PG 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.
The lab is currently pursuing how PG signaling regulates actin dynamics during follicle development. Both pharmacology and genetics reveal that PG 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 PG 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 we are determining where the PG signal is coming from, which PGs are involved, whether this is by the canonical signaling pathway, how PG 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 PGs regulate the cytoskeleton at a cellular level. Such mechanisms of PG action are likely to be reutilized throughout development, including mediating the cytoskeleton changes that occur during cancer progression and metastasis.
Undergraduate biology course work is required. Genetics and biochemistry course work preferred.
Summer students will participate in a collaborative screen to identify actin regulators mediating PG-dependent actin remodeling events. Experiments will employ a combination of pharmacology, genetics, and imaging techniques.