RNA interference (RNAi) is the surprising ability of double-stranded RNA — but not antisense RNA — to target a corresponding mRNA for destruction.  RNAi is one manifestation of a broader set of RNA silencing pathways that defend cells against external threats, such as viral infection, and internal threats such as the ‘jumping’ of transposons, and that also regulate endogenous genes, shaping gene expression during development and in response to external environmental stimuli.  RNAi has become an important tool for studying gene function in worms, flies, cultured mammalian cells, and mice, and may lead to new drugs to treat human genetic disorders.  Our laboratory studies the mechanism that underlie RNA silencing pathways in plants and animals.  The laboratory combines biochemistry with genetics and cell biology to understand the biological functions and the molecular basis of these pathways.

To study these pathways, we have developed methods to examine the RNA silencing in vitro, using extracts made from Drosophila embryos and ovaries, wheat embryos, and from cultured human and insect cells.  To ensure that our in vitro experiments faithfully recapitulate in vivo biology, we combine our biochemical tools with classical genetics and developmental biology in the fruit fly and microarray profiling in cultured human cells.  We also seek to apply what we learn about RNAi to human disease.  In fact, my laboratory, together with the laboratory of Neil Aronin, is trying to develop small RNA molecules to treat Huntington’s disease.

The best characterized types of small RNAs acting in RNA silencing are small interfering RNAs (siRNAs) and microRNAs (miRNAs). A major focus of the laboratory is to understand how these small RNAs are made, sorted into distinct "Argonaute" protein loading pathways, and how they are loaded into Argonaute proteins to form the protein-RNA complexes that mediate RNA silencing.