Cell Excretion: A Novel Mechanism of Apoptotic Cell Clearance - Apoptosis, a form of genetically programmed cell death, occurs at a high rate
throughout life in many human tissues. The resulting cell corpses are typically engulfed by
other cells and degraded in the lysosome. However, recent research has revealed that there
are other routes for elimination of apoptotic corpses as well and that defects in these
alternative cell clearance mechanisms may be linked to human diseases, including cancer.
The overall goal of this study is to characterize a novel mechanism of cell clearance in the
planarian flatworm, Schmidtea mediterranea. Preliminary data suggest that apoptotic cells in
planarians are engulfed by phagocytic cells, just as they would be in the canonical cell
clearance mechanism, but subsequently emptied into the digestive system for excretion
instead of being degraded. This hypothesis will be addressed in two specific aims. First,
electron microscopy will be used to visualize key steps in the cell clearance process in vivo,
while the roles of candidate genes predicted to play a role in engulfment will be evaluated by
RNAi and in situ hybridization. Second, RNA-Seq will be utilized to identify novel genes
involved in apoptotic cell clearance. These genes will also be characterized by RNAi and in
situ hybridization. Because planarians share key characteristics with humans, including the
utilization of an evolutionarily conserved mechanism of apoptosis, this work is likely to be
relevant to our understanding of human health and disease. This project will also offer
undergraduate students at Keene State College an opportunity to engage in discovery-based
research.