Quantitative Approaches to Study RNA-Mediated Gene Regulation

Bacteria exist in stressful and constantly changing environments. In order to to sense, respond to, and survive in various stress conditions, microbes have evolved diverse mechanisms to regulate their gene expression. RNAs, and sRNAs in particular, are prevalent mediators of gene regulation in bacteria. The identities of many sRNAs and the stresses they are associated with have often been revealed by traditional biochemical means, but a deeper understanding of the underlying physics that governs how RNAs efficiently regulate their targets could allow us to manipulate and leverage sRNAs for the sake of synthetic biology and human health. Here, I present my contributions to the quantitative study of RNA-mediated gene regulation. First, I present the general model that describes how individual kinetic parameters contribute to the overall efficacy of sRNA-mediated regulation and the hierarchy of the sRNA-regulon. Additionally, I found that certain sRNAs that have canonically been described as post-transcriptional regulators can regulate their targets co-transcriptionally. Next, I describe our recent work regarding interactions between the ribosome and the sRNA accessory protein, Hfq, and how such interactions might contribute to the sRNA target search process. Finally, I offer a set of the image analysis tools I have developed that can be utilized to study RNA-mediated regulation. In all, these tools and findings can help develop quantitative descriptions of the physics of RNA-mediated gene regulation.