Our laboratory focuses on two central problems in biology:

High-throughput RNA structure analysis.

Our vision is to address one of the great remaining and intractable problems in cellular and molecular biology -- that of determining comprehensive and quantitative structures for cellular and viral RNAs. By the structure of cellular RNA, we do not mean the relatively small pieces of RNA typically studied by biochemistry or high resolution structure approaches. Instead, we want to make it possible to understand, in detail, the global structure and long-range architecture of all cellular RNAs. To this end, we are developing a high-throughput RNA structure analysis technology involving Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (called SHAPE) with the goal of making RNA secondary and tertiary structure analysis as straightforward, in principle, as DNA sequencing is today.

We seek to understand the fundamental principles that govern function and assembly of large RNAs and RNA-protein complexes. In particular, it is our vision to extend molecular quality understanding of these reactions to very complex systems that play pivotal roles in cellular function. Current projects in this area include (i) RNA folding and protein assembly reactions central to the infectivity and pathogenesis of retroviruses and (ii) assembly of very large ribonucleoprotein complexes inside living cells.