Building a model of the molecular interactions of fertilization

About This Grant

Project Summary Fertility and reproduction have medical, social, and economic impacts on our society and the mechanisms of sperm-egg interactions are of broad scientific interest. For all sexually reproducing species, the creation of a new organism and continuation of the species relies on successful fertilization. Fertilization is the joining of an egg and sperm through proper signaling, recognition, binding, and fusion between the two gametes. A molecular understanding of the processes of fertilization has remained surprisingly elusive. Out of necessity, the field has largely focused on gene discovery and identifying proteins that function specifically in fertilization. However, with the success of these efforts we now have the need to move towards understanding the relationships between these proteins and how these proteins work together. At the same time, our gene discovery work is not finished as having a complete repertoire of fertilization molecules will be essential for a full mechanistic understanding of gamete recognition, adhesion, and fusion. C. elegans make an excellent model system to address these questions. The powerful gene discovery approaches available in C. elegans have led to the discovery of 10 sperm genes specifically required for fertilization. Loss of any one of these genes results in phenotypically wild-type sperm that cannot fertilize an egg. The discovery of this complexity has led to the model of a "fertilization synapse" where fertilization is mediated by complex cis and trans interactions of proteins at the surface of the gametes rather than any single ligand-receptor pair. Most recently, work in C. elegans has led to the discovery that proteins secreted by the sperm contribute to the fertilization synapse. This proposal aims to build a model of the molecular interactions at the fertilization synapse by 1) determining the localization of sperm proteins required for fertilization and how their expression and localization is affected by the absence of other components of the synapse, 2) characterizing a new conserved fertilization molecule, SPE-40 and 3) examining predicted interactions between SPE-40 and the secreted protein SPE-36.