Research +
Overview
RNA secondary and tertiary structure is central to the regulation of numerous biological processes, but it doesn’t always get the spotlight it deserves. As of 2022, there are approximately 1,600 RNA structures in the Protein Data Bank; this is just a fraction of the near 160,000 protein structures that have been published to date. The size, intrinsic flexibility and conformational dynamics of RNA structure make it difficult to study by standard approaches (ie. NMR, x-ray crystallography, and cryo-EM). That’s why our research group focuses on developing and applying biophysical and biochemical approaches to make it easier to study RNA structure and dynamics. Once we harness the molecular details associated with how an RNA is structured, we improve our ability to link it to the biological processes it regulates, and therapeutically target it when it is implicated in disease.
Project Areas
Unveiling the Molecular mechanisms underlying RNA chemical probing experiments
RNA chemical probing experiments enable us to study how RNAs are folded, their dynamics, and their interactions with ligands. We are interested in understanding the molecular mechanisms that underlie RNA chemical probing experiments and how these can be used to better understand the biological processes that govern everyday life.
Long noncoding RNAs
Long noncoding RNAs (lncRNAs) are multi-functional and can regulate numerous biological processes. Our group is focused on identifying the factors that enable lncRNAs to behave as multi-functional transcripts. We are interested in lncRNA splicing, lncRNA structure, and lncRNA interactions with nucleic acid and protein binding partners.
inhibition of viral infections using structure-based drug design
Many RNA viral replication processes rely on structured RNA-protein interactions. When viral RNA genomes experience mutational drift, compensatory mutations preserve the structures adopted by protein-binding RNAs. Our group focuses on disrupting the conserved RNA-protein interactions that are required for viral replication.
Approaches / techniques we frequently use
not familiar with a technique? No worries, we’re a learn-as-you-go lab. Come expand your skillset!
RNA transcription and solid phase synthesis • RNA purification • protein expression and purification • electrophoretic mobility shift assays (EMSA) • isothermal calorimetry (ITC) • nuclear magnetic resonance (NMR) • small angle x-ray scattering (SAXS) • circular dichroism (CD) • cryogenic electron microscopy (cryo-EM) • x-ray crystallography • RNA chemical probing (in vitro and in cells by capillary electrophoresis and next generation sequencing) • RNA enzymatic cleavage • sh-knockdown + RNAseq • westterrrnnnnsssss • DESeq • RNA-protein crosslinking (in vitro and in cells) • fluorescence anisotropy • RNA sequencing (Oxford nanopore) • optical tweezers • surface plasmon resonance (SPR) • molecular dynamics simulations (MD) • machine learning (ML) • bioinformatics • high-throughput drug screening • the list evolves as our projects evolve 🙂
Cash Money
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Folding and Structural Ensemble of the Nascent HIV-1 RRE RNA |
Dean’s Undergraduate Research Fund Spring 2024Ethan Arnold: Frances and Benjamin Benenson Research Scholar – Leveraging RNA 2D Structure to Optimize RNA Interference for Noncoding RNAs Daniel Cohn: Using SHAPE-Map and Protein Titrations to Study Protein Binding Events with Conformationally Dynamic RNAs Jenayah Dunn: Investigating the interaction of U2AF proteins with long noncoding RNAs to assess their role in splicing Isabella Lee: Binding Shift Assays and SHAPE MaP Analysis to Investigate the Role of hnRNPC in the Splicing of LINC00624 Fall 2023Ethan Arnold: Identifying Statistical Correlations Between RNA Atom-Atom Distances and Chemical Reactivity Daniel Cohn: Using Chemical Probing and Mass Spectrometry to Assess Protein Binding with Conformationally Dynamic RNAs |