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. 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 creating new high-content "chemical microscopes", including Selective 2'-Hydroxyl Acylation analyzed by Primer Extension (SHAPE), that enable generic and highly accurate RNA secondary and tertiary structure analysis.
Structure and Function in the Transcriptome
We then apply these new approaches to compelling, and otherwise intractable, problems in biology. 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. Students in the lab meld and, collectively, make use of the methods of physical and mechanistic biochemistry, bioorganic chemistry, structural biology, virology, microbiology, and computational bioinformatics and biophysics. Current projects include (i) RNA-mediated reactions central to the replication of human viruses, (ii) biomedically important ribonucleoprotein complexes inside living cells, and (iii) facile analysis of small molecule binding to RNA.