This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
Although fusion of sperm and egg to form a new organism was first observed microscopically over 160 years ago, the proteins on the surface of the sperm and egg that facilitate this process are still largely unknown. Over the last decade, the small (~1mm) nematode worm C. elegans has been used to discover seven sperm proteins and six egg proteins that are required for fertilization to take place. The focus of this proposal is SPE-42, a protein that, when mutated, results in complete sterility of the affected worms. Preliminary data, including computer models, suggest that SPE-42 is expressed on the sperm surface, meaning that SPE-42 is potentially available to interact with proteins present on the egg surface. The experiments to be carried out will test this hypothesis by asking (1) where in sperm is SPE-42 located and (2) which parts of the protein are important for its function. A combination of molecular genetic techniques and computer modeling of the SPE-42 protein structure will be used to complete the proposed work. In addition, a collection of new fertilization-defective mutants will be evaluated to find other proteins that are involved in sperm - egg interactions during fertilization. The knowledge gained from these experiments will impact both the fields of infertility treatment and non-hormonal contraceptive development. Americans spend nearly $1.4 billion per year on infertility treatment, and most of the bill is not covered by medical insurance. Because proteins similar to SPE-42 are found in nearly all multi-cellular organisms including humans, what we learn about how SPE-42 works will inform our understanding of animal fertilization in general. This project will provide hands-on training to at least two graduate students and several undergraduates.
