Our laboratory is focused on understanding the "rules" that govern RNA function. We study early development and neuronal plasticity given the pervasive use of post-transcriptional controls in both contexts.
Q1. How do proteins differentiate between similar if not nearly identical regulatory elements? A sizable fraction of our genes (ca. 5%) encode RNA-binding proteins. An essential aspect of understanding their function is probing the specificity for RNA. To form distinct post-transcriptional regulatory networks, RNA-binding proteins must discriminate between similar sequences and structures to achieve specificity. Unbiased assessments of the intrinsic preferences of proteins for RNAs are an invaluable tool for understanding this foundational problem. We develop genomics tools to make this goal achievable. We collaborate with Faruck Morcos on this problem.
Q2. How do RNA-binding proteins control plasticity? Sensory neurons, termed nociceptors, undergo remarkable changes in activity after an injury. These changes require protein synthesis but the identify of sequence-specific RNA-binding factors that decide which mRNAs are controlled are unclear. We generated the first class of RNA decoys for the purpose of identifying these factors in mouse models. We make use of quantitative measurements of behavior and inflammation. We collaborate with Ted Price on this problem.
Q3 How are RNA-protein interactions hardwired? Throughout evolution, RNA-binding proteins have expanded through gene duplication. Extant genes can display remarkable differences in what RNAs they preferentially associate with but how does novel specificity arise? We are interested in addressing what are fundamental aspects of functional diversity with a focus on the role of allosteric regulation via protein-protein interactions in RNA control. We collaborate with Te-Wen Lo, Traci Hall, and Aaron Goldstrohm on this problem.