Understanding within-cell plasmid evolution with synthetic systems

This project seeks to develop our understanding of the biology and evolution of plasmids, small DNA molecules that can transfer traits like antibiotic resistance between distantly related bacteria. The research will develop novel experimental tools and techniques that will be shared broadly with the scientific community. The project will also create engaging educational videos to teach evolution concepts to students and the public and develop low-cost tools for fluorescence experiments suitable for research and teaching labs. These efforts aim to make cutting-edge science more accessible and understandable to a wide audience. The research will investigate how plasmids compete and evolve within bacterial cells, a process critical to understanding bacterial adaptation but previously difficult to study experimentally. Using synthetic biology approaches, the researchers will construct artificial plasmid systems that allow precise measurement of intracellular plasmid competition. They will examine tradeoffs between gene expression and plasmid fitness, probe the molecular mechanisms involved, and explore how selection acts on plasmids across different scales. The project combines experimental techniques like microfluidics, fluorescence imaging, and DNA sequencing with theoretical modeling to gain insights into the evolutionary dynamics of these important mobile genetic elements in bacteria. This work has the potential to transform our understanding of horizontal gene transfer and bacterial evolution, with implications for predicting and potentially manipulating the spread of traits like antibiotic resistance. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.