INVESTIGATOR: Kathryn Ramsey, University of Rhode Island
MENTOR: Steven Gregory, University of Rhode Island
THEME:  Environmental Health Sciences

ABSTRACT: The rising incidence of tickborne diseases is a public health threat in the United States. A particularly infectious tickborne pathogen and potential bioweapon, the Gram-negative intracellular pathogen Francisella tularensis, can be transmitted to humans through arthropod vectors, aerosolization, or contaminated food or water. How F. tularensis controls gene expression to adapt to these diverse environments is not understood and much remains to be learned about gene regulation in this pathogen. The goal of the proposed work is to determine how distinct ribosomal protein (r-protein) paralogs influence ribosome function to control gene expression and virulence. Preliminary work lead us to a model in which “specialized ribosomes,” or ribosomes with distinct composition and function, are created in F. tularensis by incorporation of different r-protein paralogs and control gene expression at the level of translation. Our proposed aims will address this model by identifying how a particular r-protein paralog influences expression of specific genes at the molecular level and how r-protein paralogs influence transcription and translation genome-wide. Together, these studies will yield specific information about how F. tularensis controls gene expression at the level of translation, provide new avenues of investigation in ribosome biology, and may significantly impact how we design ribosome-targeting antimicrobial therapeutics. Finally, our results may shift our view of bacterial ribosomes from constitutively functioning units to highlight their potential as programmable and regulated machines, a finding which may be applicable to virtually all bacteria.

HUMAN HEALTH RELEVANCE: Vectorborne and zoonotic diseases are an ongoing and increasing public health threat in the United States. The work proposed here will improve our fundamental knowledge of tickborne disease and potentially reveal novel targets for antimicrobial drug development.