Project Summary/Abstract Infertility impacts one in five couples globally. For many of these couples, the sperm and egg look morphologically normal. This complicates determining treatments for infertility. Despite the societal burden of infertility and the need for reproductive control through new contraceptive targets, the genes and molecules required for fertilization particularly the genes on the egg side are still largely unknown. The persistent lack of molecular mechanisms surrounding fertilization often hinders determining therapeutic interventions. There are many reasons that it been difficult to find egg function genes. This spans from redundant gene function, pleiotropy, lack of validation from biochemical approaches, and challenges in maintaining sterile mutants. These challenges highlight the importance genetic approaches to understand the genes required for these mechanisms. I will use the Caenorhabditis elegans model system to conduct this research as it has a high percentage of genetic homology with mammals, a quick generation time, and robust genetic tools. To facilitate the identification of egg function genes, I designed and validated a forward genetic screen in Caenorhabditis elegans using newly available balancer chromosomes to isolate uncharacterized genes involved in egg binding and fusion as well as factors required for egg activation/the oocyte to embryo transition. This proposal will determine the molecular mechanism of several of these newly discovered genes. I propose the following research aims: 1) Investigate the molecular function of PGM-3 in the oocyte 2) Explore the effects of a newly identified sperm supplied factor required for egg activation 3) Characterize other new gamete function mutants that were previously identified. This mentored postdoctoral period of funding will provide me with the time and resources to learn super resolution microscopy and proximity labeling as well as the skills to navigate a career as an independent researcher. These skills are essential for my future career development goals which include obtaining a faculty position and leading my own research program. To facilitation completion of these goals, I have established a scientific advisory committee and a career development mentoring committee. Each are comprised of experts in my field to assist me in my training. I also propose taking a microscopy course to ensure that I have formal training in this complex subject. The K99 portion of this award will take place at Rutgers University which has both a robust research and career development infrastructure for postdoctoral training. The K99/R00 funding mechanism will allow me to learn and apply novel technology to accelerate discovery of the molecules required for fertilization.