Steve L. Bonilla, Ph.D.

Research

My lab investigates how RNA molecules fold into three-dimensional structures to drive complex biological processes. In particular, we want to understand how viruses use dynamic RNA structures in their genome to hijack the cellular machinery of their host and regulate their life cycles. Understanding these processes will allow us to identify RNA structures that can be targeted by small molecules for the development of novel antivirals. 

Viruses consist of little more than genetic information wrapped in a protective protein coat. Some viruses—such as dengue, Zika, yellow fever, and human immunodeficiency virus (HIV)—carry their genes in the form of RNA. This RNA not only contains the instructions needed to make the proteins necessary for viral replication, but it can also fold into structures that physically interact with host and viral proteins to co-opt the biochemical machinery of the cell. Yet how viral RNAs adopt the range of three-dimensional configurations needed to engage with the host components is not understood, in part because RNA’s inherent flexibility makes it hard to study via standard structural methods. Now, using state-of-the-art techniques in single-molecule biophysics, cryo-electron microscopy, and computational modeling, we will visualize the dynamic structural ensembles adopted by the RNAs of important human-infecting viruses—such as dengue and Zika—as well as plant-infecting viruses that serve as useful model systems for understanding generalizable principles. Using the structural models derived from our studies, we will then introduce mutations into the viral RNA that are predicted to stabilize or disrupt certain structural intermediates and determine how these alterations perturb viral function—findings that could point toward RNA structures that are targetable by novel antiviral therapeutics.