Broadly speaking, we are interested in understanding the causes of variation in rates and patterns of molecular evolution. Our bacterial wet-lab work focuses on the evolution of antibiotic resistance, and patho-adaptation more generally. We also use comparative methods to investigate molecular evolution in both prokaryotes and eukaryotes.
Ongoing projects in the lab include:
- Genetic interactions of antibiotic resistance mutations in bacteria: The study of genetic interactions – also known as epistasis – is integral to contemporary systems biology and to evolutionary genetics. Genetic interactions can provide insight into the functions of previously uncharacterized genes, and can indicate whether genes participate in the same or in parallel pathways. Moreover, in the evolutionary genetics literature, theory and experiment have suggested vital roles for epistasis in determining the trajectory of evolution, in the evolution of sex, and in determining rates of adaptation. Notably, epistasis has important implications for antimicrobial resistance: compensatory mutations that ameliorate costs of resistance often have genotype-specific effects, and there is promise in leveraging epistasis to develop new antimicrobials. We carry out targeted and high-throughput screens to characterize genetic interactions in E. coli, and we use laboratory selection experiments to investigate the evolutionary consequences of epistasis.
- Pathogen comparative genomics: We use comparative genomic methods to understand the population structure of pathogens, and to identify genomic loci contributing to pathogen adaptation. One current study focuses on the evolution of quinolone and beta-lactam resistance in E. coli.