Structure, Function, Evolution, Systems Biology, and Biotechnology
Our laboratory studies gene expression, RNA splicing, mobile self-splicing introns, and retroviral-like genetic elements in eukaryotes and prokaryotes. We are interested in mechanisms by which mobile introns integrate site-specifically into DNA, how proteins promote RNA folding and RNA catalysis, the mechanism and function of RNA helicases and their relationship to cancer, the evolution of introns and splicing mechanisms, and the evolution and origin of retroviruses and reverse transcription. Our research employs a combination of genetic, biochemical, molecular biological, and structural approaches. In practical applications of our work, we have used mobile group II introns to develop a new type of gene targeting vector, dubbed "targetron", which can be programmed to insert efficiently into desired DNA sites. Targetrons are widely used for the genetic engineering and systems biology of diverse bacteria, and we are developing methods for using them in higher organisms, with potential applications in gene therapy. Our work on mobile group II introns led to the discovery of a new family of intron-encoded reverse transcriptase. We are studying these enzymes biochemically and structurally and have developed them as tools for applications in next-generation RNA sequencing, transcriptome profiling, analysis of RNA structure and RNA-protein interactions, and diagnostics. These novel reverse transcriptases open new approaches, which we are using in the lab for the discovery and profiling of miRNAs and other non-coding RNAs involved in important biological processes and human diseases.