Our Research Projects

The mechanics of sRNA-mediated gene regulation in E. coli

In E. coli, there are more than 100 distinct sRNAs that regulate gene expression by base-pairing with mRNAs. sRNA-mRNA base-pairing can lead to changes in mRNA translation or stability depending on the nature of the interaction. These sRNAs fall into distinct classes with some utilizing Hfq, ProQ, both Hfq and ProQ, or neither Hfq nor ProQ. Our goal is to understand at a molecular level how these different class of sRNAs regulate distinct mRNAs, and how this regulation alters particular aspects of E. coli physiology or behavior.

RNA decay in E. coli

While most of the RNases that perform RNA decay in E. coli have been identified, much remains unknown about even the most extensively studied ones such as the exoribonuclease polynucleotide phosphorylase (PNPase) and the endoribonuclease RNase E. We are focused on understanding at a molecular level how these RNases function.

The infrastructure for sRNA-mediated gene regulation in S. pneumoniae

In Gram-negative bacteria such as E. coli or Salmonella species, much is known about the proteins involved in sRNA-mediated gene regulation including chaperones involved in protecting sRNAs from RNases and facilitating sRNA-mRNA annealing and RNases carrying out the decay of sRNAs and their target mRNAs. Nearly all of these proteins are absent from the genome of the many Gram-positive bacteria including S. pneumoniae. What are the proteins that carry out these functions and how do these factors do it? Using bioinformatic and genetic approaches, we are identifying these players, and utilizing genetic, molecular, and biochemical methods, we are elucidating their roles in sRNA-mediated gene regulation.

The contribution of sRNAs to S. pneumoniae host colonization, dissemination, and transmission.

More than 100 sRNAs have been identified in S. pneumoniae by us and other research groups, yet almost nothing is known with regards to the role of these sRNAs in the regulation of S. pneumoniae virulence determinants. Our research is focused on elucidating the contribution of distinct sRNAs to specific aspects of S. pneumoniae pathogenesis using high throughput RNA sequencing, genetic, molecular, and biochemical based approaches.