Characterizing Competition Between Virulent and Temperate Phages for Biofilm-Residing Host Bacteria - ABSTRACT The human gastrointestinal tract is densely colonized by bacteria that are under threat of infection by phages. To combat threats, bacteria commonly form groups, termed biofilms, comprised of bacterial cells and secreted adhesive matrix. Temperate phages differ from virulent phages as they can either lyse their host cell to produce a burst of new virions, or they can integrate into the host genome and propagate vertically, reserving the ability to enter the lytic cycle under specific environmental conditions. Despite the ubiquity of temperate and virulent phages, the fundamental patterns of how these different life strategies fare when in direct competition within a structured community has never been explored on cellular spatial scales. The first aim of this proposal is to determine competition dynamics between temperate and virulent phages within a biofilm context. We will determine how host availability within structured and unstructured microbial communities alters this competition. We will then determine optimal invasion dynamics for temperate phages as a prophage or as an active virion, as well as how temperate phages propagate through biofilms after prophage induction. The second aim of this proposal is to explore the social evolution of temperate phages. In environments where virulent phages are able to successfully infect bacteria lysogenized with temperate phages, the virulent phages always outcompete temperate phages. How then do temperate phages evolve? We will investigate how temperate phages can win in a global population through the evolution of restraint while still being outcompeted in discrete microenvironments. We will investigate this question in both laboratory experiments and theoretical modeling work. This work will provide medically relevant insight into the interplay phages attempting to colonize and infect residing host bacteria in humans. The proposed training plan encompasses the acquisition of various skills, including the mastery of laboratory techniques, enrollment in an off-campus course at Cold Spring Harbor, the development of effective experimental designs, proficient science communication, and the cultivation of active mentorship abilities. Dartmouth College and my mentorship team are highly equipped to assist in the successful execution of my research project and facilitate my advancement to the next stage of my career as a postdoctoral researcher, with the ultimate goal of securing a faculty position at an R1 institution.
