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 establishing comprehensive and quantitative structure-function relationships for intact 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 several high-throughput RNA structure analysis technologies including 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.

Complex RNA Folding and RNA-Protein Assembly Reactions

We seek to understand the fundamental principles that govern function and assembly of large RNAs and RNA-protein complexes. In particular, we use the high-throughput technologies created by our laboratory to study very complex systems that play pivotal roles in cellular function and human disease. 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 large and biomedically important ribonucleoprotein complexes inside living cells.

Structure of an HIV RNA Genome