In nature, animals grow up in different and often changing environments. Harsh environments such as cold weather or inadequate food can cause animals to slow their growth or even pause growth altogether. Despite this severe interruption to their development, if the environment improves, animals will continue their growth and ultimately become normal adults. The genes and proteins that allow animals to develop normally after a long interruption are unknown and are a major knowledge gap. This project builds on previous work from the PI to study this question in the microscopic nematode C. elegans. These worms are a valuable model because of their simplicity and ease of use for experiments. Furthermore, C. elegans shares 7,663 genes with humans, meaning that what we learn from C. elegans is often relevant across species. As part of this study, a new program will engage student teachers in research. This program will foster teacher-leaders who will then provide effective STEM education at the K-12 level. This education is critical for the US to maintain its leadership in scientific disciplines, and to provide students with skills that employers value. Furthermore, this study will result in the training of many undergraduate and graduate students, both in the PI's research lab and in lab-based courses taught by the PI.
The proposed work capitalizes on the power of C. elegans as a model to elucidate mechanisms that enable development to occur normally after diapause. In favorable environments, C. elegans develops continuously through four larval stages separated by molts. In contrast, adverse environments promote entry into diapause ("dauer") midway through larval development. Despite this interruption, if favorable conditions are again encountered, development proceeds normally due to the modulation of developmental pathways and re-setting of cell fate. Prior work from the PI indicates that the potentiation of microRNA activity is a key component of the post-dauer developmental program. This project builds on that work to discover and characterize factors involved in post-dauer microRNA pathways. Preliminary data suggest that two transcription factors, ZTF-16 and FOXO/DAF-16, are important players in the post-dauer pathway. Genetic and molecular experiments will test the hypotheses that ZTF-16 is a microRNA target and that FOXO/DAF-16 is a modulator of microRNA activity. In addition, genomic approaches will identify factors that enable proper post-dauer development. Completing this project will define mechanisms by which microRNA pathways that control cell fate are modulated after dauer and lay the foundation for future work.
