Dissecting small RNA pathways using comparative genetics and genomics in C. elegans and C. briggsae

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RNA interference (RNAi) is a cellular process whereby the expression of a specific gene is silenced by the action of an enzymatic complex composed of a small RNA molecule acting with an Argonaute protein. These small RNA molecules provide sequence-specific gene targeting activity to the Argonaute, which is the catalyst of silencing. RNAi has been the topic of much interest over the past decade, during which time it has become a nearly ubiquitous laboratory tool, revolutionizing studies in some research systems that were previously genetically intractable. RNAi also holds great therapeutic potential; imagine being able to turn off a specific gene that contributed to cancer progression at will, thus halting oncogenesis. Other cellular mechanisms closely related to RNAi are conserved in various organisms, from plants to worms and humans. Such endogenous gene silencing pathways play key roles in regulating gene expression during normal processes such as cell differentiation, development, and gamete formation. Thus, studies of endogenous silencing will reveal a deeper understanding of the basic cellular functions that contribute to development and differentiation in various organisms. The tiny nematode C. elegans has proven an ideal model for understanding the molecular mechanisms of RNAi and endogenous small RNA pathways. Accordingly, we will use C. elegans and a distinct nematode species called C. briggsae to better understand the evolutionary differences in small RNA-mediated gene regulatory mechanisms, and to increase our overall knowledge of the molecular mechanisms of these critical gene silencing pathways.