Grant: CIHR Fellowship

Understanding the mechanisms by which individual cells within an organism overcome stress and damage throughout their birth, growth, and lifetimes is critically important for our understanding of human development and disease. Cells in the early embryo are incredibly robust to sources of damage, including DNA mutations. The responses of cells to damage during embryogenesis mirror the mechanisms that occur in cancer cells, allowing them to survive and proliferate in the presence of deleterious mutations. The Schier lab has recently identified a new population of cells within the early embryo using a combination of computational and genetic experiments (Satija et al, Nature Biotech, 2015). These cells respond to DNA damage by activating a novel cellular mechanism related to programmed cell death (apoptosis). Because they avoid cell death in the presence of damage, the Schier lab coined these the 'seven-sleeper' cells. They were named after the Seven Sleepers of Ephesus, who took cover from prosecution in a cave before emerging once the danger had passed several years later. I propose to completely dissect the developmental origin, function, and ultimate fate of these cells. I will use a combination of genetic, pharmacological, imaging, and computational tools to characterize the 'seven-sleeper' cells. I aim to answer questions about why this program is activated during embryogenesis, how it relates to known mechanisms of apoptosis, and dissect exactly how it works to protect damaged cells. Observations made by me, and results I generate can be translated, and my long-term goals are to add to our understanding of the cellular mechanisms of DNA repair and the regulation of cell death in cancer and other diseases.