We have generated a mouse knockout for the gene called Dicer, which is the catalytic engine of small RNA production in cells. We are using this mouse to explore the role of small RNAs in developmental and immune biology settings. The roles of small RNAs may be much broader than anticipated, thus Dicer may be a ‘master regulator’ in a number of different contexts. Genetic data in C. elegans indicates that Dicer depletion results in loss of the ability to do RNA interference and developmental defects. In S. pombe, knockout of Dicer results in loss of heterochromatic silencing, suggesting a potential role for small RNAs in transcriptional gene silencing. In fact, evidence is accumulating that small RNAs may key mediators in DNA methylation. We believe that the small regulatory RNAs that have discovered are just the ‘tip of the iceberg’ in a set of important biologies that we are far from understanding.

Current projects include the use of RNA expression arrays (both mRNA and microRNA), mouse transgenics (both knock-outs and knock-ins), and biochemical approaches in cell culture aimed at dissecting mechanisms of small RNA biology.