The overarching, longstanding aim of the Sontheimer Laboratory is to uncover and understand the roles of RNA molecules during gene expression. This research has included studies of splicing mechanisms and noncoding RNA function in Saccharomyces cerevisiae and studies of RNA interference and related pathways in Drosophila melanogaster and in cultured human cells.
Our current emphasis is on mechanisms of genetic interference pathways specified by CRISPR loci in pathogenic bacteria. We have employed biochemical, molecular biological, and genetic approaches to uncover the fundamental principles that govern these processes, with considerable success. Most notably, we demonstrated in 2008 that the molecular target of CRISPR interference is DNA rather than RNA, setting the stage for the recent explosion in CRISPR-based genome manipulation.
More recently we have identified unique features of the CRISPR/Cas pathway in meningococcus and demonstrated the suitability of this system as a platform for genome editing in human pluripotent stem cells. We are now poised to extend this and other capabilities of CRISPR-Cas systems to accelerate biomedical research and treat human disease.