Sirena Tran

One of the most pressing clinical challenges that we are currently facing today is the antimicrobial resistance (AMR) problem. Historically we have been trying to battle this problem by creating more potent antibiotics. However, it has become evident that this approach is failing. Part of the efforts in the Cover lab are focused on the development of an alternate strategy to resolve this problem: inhibiting evolution. As the first step towards this goal, the lab is identifying and characterizing proteins that accelerate evolution (“evolvability factors”). One of these proteins is the DNA translocase and RNA polymerase interacting protein, Mfd. The lab has recently found that Mfd is required for the rapid development of AMR, to multiple classes of antibiotics in highly divergent bacteria. However, it is unclear 1) how Mfd increases mutagenesis and 2) whether the microbiome impacts Mfd-dependent AMR development (or AMR development in general). To investigate these questions, Salmonella typhimurium will be used as the model system with various biochemical, molecular biology, and genetic techniques. Additionally, a mouse model of evolution will be developed where we can both monitor the kinetics and degree of AMR development in bacterial pathogens in “regular” versus germ-free mice with and without Mfd.

Mentor: Timothy L. Cover, M.D.