Germ cells are immortal. They are uniquely poised to sustain life across generations through the fusion of oocyte and sperm. Despite the central importance of germ cells to life, a clear understanding of the molecular events that control their formation is lacking. Germ cells are set aside from somatic cells in the embryo and go through specialized meiotic cell cycles as the animal matures. These cell cycles are interspersed with long periods of arrest. In human females, meiosis I is initiated in the fetus. At birth, oocytes are arrested in meiosis I; after puberty, every month an oocyte initiates meiosis II – ovulation. Upon sperm availability these cells are fertilized, generate an embryo, and the cycle-of-life continues. During meiotic I progression and arrest, the fitness of oocytes and their progeny are influenced by environmental cues and signaling pathways. Yet, little is known about how these factors influence oocyte development and embryo fitness. Using Caenorhabditis elegans, we study the influence of the RAS/ERK pathway on female meiosis I progression. Our research focuses on understanding how the RAS/ERK pathway acts through a battery of substrates to direct multiple cell biological events during meiosis I; how environmental cues impact the RAS/ERK pathway and meiotic progression.
Our laboratory is interested in understanding the molecular and genetic factors that dictate the fitness of the maternal gametes. Specifically, we focus on identifying the function of proteins that are phosphorylated and regulated by environmental signaling and the RAS/ERK pathway to execute different response, and the impact of each response on gamete fitness.
We have identified different ERK target proteins that function during germ cell development in C. elegans. Currently, we approach each ERK target one at a time, and using a combination of transgenic methods, phosphorylated antibodies, Crispr mediated gene edits and powerful imaging techniques, we are beginning to delineate the role of individual ERK target proteins in differing events of meiotic progression, oocyte development and embryo fitness.
Given the conserved events of meiotic progression, and the RAS/ERK signaling pathway, our research holds the promise of not only uncovering the molecular control of meiosis I at unparalleled resolution to enable better understanding of factors that dictate maternal health and thus progeny survival, but also is poised to uncover novel ERK targets that are regulated during oncogenesis.