CAREER: Stress, Recovery, Regeneration, and Resilience in Reproduction

About This Grant

All living things, including humans, experience trade-offs between directing energy to their own cells and organs, versus directing energy to the reproductive system cells that will make the next generation. The trade-off becomes more complex when animals face cellular stresses caused by short-term difficulty (like starvation), or long-term damage due to aging. These questions are hard (and expensive) to address in long-lived animals; for example, lab mice in aging studies live about two years. This project uses a small short-lived worm (lifespan of weeks to months) that shares many genes and cellular properties with humans, to ask questions about how animal cells and organs respond to starvation at different ages, and how those responses affect the animal’s ability to reproduce later in life. Broader Impacts include creating hands-on and lecture-based courses in developmental biology for undergraduates, and coordinating with a clinical professor at the UNC School of Nursing to teach seminars to nursing students about the biology of pregnancy and human development. C. elegans nematode worms have an alternative developmental stage called “dauer” that is induced by early larval starvation and crowding. Dauer larvae can live for several times longer than the normal lifespan of a worm without eating or noticeably aging. After conditions improve, the worms rapidly resume feeding and growing, and their subsequent lifespan is unaffected by the time spent as dauers. For that reason, dauers have long been considered to be “non-aging”. Recent discoveries in support of this work demonstrate that dauers lose well over half of their germline cells during their first month in the dauer state. Germline shrinking also occurs in starved adults. In adults, differentiation contributes to germ cell loss, but in dauers it does not. After conditions improve, both dauers and starved adults rapidly regenerate the germline and commence producing healthy offspring. This work will investigate the molecular and cellular basis of starvation-induced germline shrinkage and recovery at a genetic level at these two ages. To integrate teaching into this research, a new undergraduate teaching lab will screen for genes required for germline recovery by RNAi knockdown. Candidate pathways include Wnt, Netrin, Notch, insulin-like signaling, programmed cell death, autophagy, and DNA repair, all of which are conserved with humans. This research is funded by the Cellular Dynamics and Function Program of the Division of Molecular and Cellular Biosciences. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.