Identifying limitations on microbial host jumps

Of all the potential pathogens around us, we, like other multicellular species, can typically be infected by only a small subset. However, when a microbe manages to break such host barriers, it can quickly spread through the new host population. To predict when a pathogen will make a host jump, we need to understand what limits pathogen adaptation to different host environments. My research program focuses on investigating the factors that limit the adaptation of microbes to new host environments. Specifically, I address this question from the perspective of an evolutionary geneticist and microbiologist. I identify bacterial genetic mechanisms important for colonizing different hosts and use comparative and functional genomics to understand how they evolve. Recent work from myself and others demonstrated that both host genetics and the surrounding microbes influence the ability of a pathogen to move between hosts. The relative importance of host genetics and surrounding organisms as well as interactions between these factors are largely unknown. I recently developed a study system in the broad host range bacterial genus Pseudomonas that lays the groundwork for studying what limits the adaptation of pathogens to new hosts. My lab is now developing methods to identify genome-wide those loci in Pseudomonas important for colonizing different host environments. We have also curated natural variation data for thousands of Pseudomonas genomes collected from diverse hosts. Ongoing efforts are determining the associations between Pseudomonas genetic variation and differences in pathogen specificity. Over the next five years, the focus of my research program is to determine the relative importance of host genetics and surrounding microbes in limiting Pseudomonas adaptation to new hosts. To address this question, I will lead projects under three broad themes: (1) identify how surrounding microbes constrain evolution of Pseudomonas to a new host (2) determine how the genetic requirements for colonization change across host species (3) determine how horizontal gene transfer influences Pseudomonas adaptation to new hosts. Together these three projects will contribute to our understanding of how host genetics and the surrounding microbes influence Pseudomonas adaptation. I have selected these projects to start my lab because the question of what limits bacterial adaptation is a question generalizable to all bacteria. The mechanisms we discover are likely to be relevant to the study of other bacteria as many bacterial species share mechanisms of colonization, and this work is also relevant more broadly to general questions about niche evolution. My long-term objective is to use the knowledge gained from these studies to predict which microbes will undergo host jumps.