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Using the nematode Caenorhabditis elegans, our laboratory takes a molecular genetic approach to investigate questions regarding sperm differentiation and function.
Our major strategy is to identify mutations that make sperm defective and then to use a combination of molecular cloning and genetic analysis to study the functions of the genes defined by these mutations. Several spermatogenesis genes we have identifed closely resemble human genes, and we expect that some of our findings will apply to human genes as well.
We study spermatogenesis and fertilization in the nematode Caenorhabditis elegans because of its superior genetic and reproductive biological tools. Like mammals, the C. elegans spermatid surface must be remodeled by secretory vesicle fusion in order for cell-cell fusion to occur during fertilization. Consequently, we focus on mutants that are either directly defective in fertilization or defective in the sperm secretory vesicles (analogous the the acrosome in mammalian sperm) that must fuse to generate a fertilization-competent surface. We are currently focused on the developmental control of sperm vesicular acidification and how this relates to fertilization. We showed that the vacuolar ATPase regulates sperm vesicle acidification using genetic and pharmacological approaches. Using pH sensitive vital dyes, we discovered a mutant defective in vesicular acidification and showed that it encodes an ubiquitin E3 ligase. At least two of the seven known fertilization defective mutants encode membrane proteins that are placed on the sperm surface by secretory vesicle fusion. We are currently exploring how acidification of sperm secretory vesicles prepares them to deliver proteins to the spermatozoon surface so that it can participate in fertilization.
