Title: Helping People through RNA Structure
Abstract: The genomic era spurred a new phase of discovery, including the expanded regulatory roles of RNA that act via RNA structure, RNA modifications, and coordinated binding of RNA-binding proteins that together specify gene expression. These genomic approaches have been foundational to discovery but do not provide the quantitative information that will needed to predict gene expression. In contrast, biochemical approaches have predictive ability, by determining the kinetic and thermodynamic constants that describe transition rates, conformational states, and interactions. However, biochemical approaches have lacked the scale needed to address cellular complexity. To understand how these interactions regulate the gene expression program and modulate them for therapeutic intervention, we need predictive models for RNA structure and protein-binding—for an arbitrary RNA sequence—and we need to be able to predict their functional outcomes.
To address these questions requires systematic and quantitative approaches that extend beyond traditional functional genomics. Accordingly, I have developed high-throughput cellular biochemistry (HTCB) to bring biochemistry to genomic scale in cells. Using a designed library that varies individual RNA features that contribute to folding combined with DMS-MaPseq chemical probing, we measured the thermodynamic stability of thousands of RNA structures in vitro and in cells. This method allows for the quantification of differences in RNA structural ensembles in and out of cells, of the extent cellular unfolding, and of deficiencies in standard computational models used to predict RNA structures. With this, I can establish a comprehensive model for RNA folding in cells that is predictive, testable, and can be extended to relate the energetics of RNA structure to downstream effects on gene expression.
Bio: Lauren was born and raised in Birmingham, AL. She earned her Ph.D. in Chemistry at the University of Illinois at Urbana-Champaign combining organic synthesis and chemical biology developing RNA- and DNA-targeting drugs under the mentorship of Prof. Steve Zimmerman. She is currently expanding her expertise in RNA biology from translational to fundamental, combining biochemistry and genomics to study RNA interactions in cells as a HHMI Hanna H. Gray Fellow advised by Prof. Dan Herschlag (Stanford) and Prof. Silvi Rouskin (Harvard Medical School). In her independent lab she plans to combine fundamental biochemistry with drug discovery to predict the effect of RNA modifications on gene expression and to design new therapeutics and chemical probes for RNA- mediated diseases and processes.
Key Words: RNA structure; Drug Discovery; quantitative predictive models
Host: Prof. Tina Wang