Faculty in the Department of Molecular Biosciences

Lisa Timmons Ph.D., Johns Hopkins Assistant Professor 5041 Haworth (785) 864-7363; email: timmons@ku.edu Double-stranded RNA (dsRNA) was discovered to have the ability to interfere with gene function in a sequence-specific manner in the model genetic organism Caenorhabditis elegans. dsRNA with sequence homology to that of an endogenous gene or transgene can induce silencing of the corresponding gene or transgene--a process that has been termed RNAi (for dsRNA-mediated genetic interference). RNAi and related gene silencing phenomena have been observed in a number of different plant and animal species, including humans. RNAi has proven a valuable tool in the analysis of gene function, especially for organisms that would otherwise not be amenable to genetic analysis. RNAi is an mRNA degradation mechanism that is triggered by dsRNA and is principally active in the cytoplasm of cells. The RNAi mechanism is potent and serves to protect cells from invading foreign genomes (many viruses and transposable elements have dsRNA features). A common feature of RNAi and other responses to dsRNA is that the responses are triggered by entry of dsRNA into cells. Work from our laboratory is aimed at uncovering the mechanism by which dsRNA enters cells and traffics throughout an organism. Previous work has demonstrated that RNAi of large populations of C. elegans can be achieved using a novel dsRNA delivery strategy, EXIT of dsRNA from cells can be observed using a novel "spreading assay", mutant C. elegans that are defective in dsRNA uptake/spreading can be obtained, and tissue-specific forms of dsRNA uptake exist in C. elegans. These results, assays, and mutant animals form the groundwork on which future experiments will be based.

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