RNA structural dynamics and ligand recognition
Noncoding RNA and ribonucleoproteins (RNPs) perform essential biological functions such as transcription regulation, RNA splicing, RNA processing, and translation, yet the sophistication with which these regulatory elements direct cellular activities is only beginning to be elucidated. These processes are highly dynamic, often with RNA conformational and structural transitions that accompany protein recognition. Failure of these RNAs and RNPs to properly fold and assemble can give rise to diseases such as blood and solid tumor cancers, heart disease, and neurodegeneration. Despite its medical significance many questions remain regarding how RNA folds, assembles with specific proteins in the correct order, and carries out discrete functions.
Our research program uses integrated structural biology, biophysical, and chemical biology tools to investigate the folding and function of regulatory RNAs and RNPs. We aim to elucidate the biophysical properties governing RNP assembly and stability in order to achieve a rigorous understanding of how RNPs regulate gene expression in healthy individuals, and how dysfunction leads to divergent disease phenotypes. The principles deduced from these studies will provide valuable information on RNA conformational dynamics, RNA-protein recognition, and mechanisms of hierarchical protein assembly onto structured RNAs, enabling future studies to probe the mechanism further in vivo and informing the design of therapeutics to target diseases caused by improperly functioning regulatory RNPs. We take a highly interdisciplinary approach using solution NMR spectroscopy, X-ray crystallography, and electron microscopy, as well as biochemical and biophysical methods to investigate RNA structure and dynamics, RNA-protein interactions, and RNP function.
Research in the laboratory provides diverse training opportunities in spectroscopy, calorimetry, structural biology, biophysics, computational modeling, chemical biology, and biochemistry. We are actively looking for additions to the team! Please email us with a brief description of your research interests, past research experience, and CV/resume.