The evolution of host manipulation by bacteriophage.

The idea of parasite manipulation is well known in animal behaviour, with famous examples like the cordyceps ?zombie? fungus of ants. Yet, the most abundant and diverse parasites on earth do not target animals but rather bacteria. They are the bacteriophages, or phages. My hypothesis is that it is in phages that we will find the most important examples of parasite manipulation, examples that will help us both understand and control bacteria, and their impacts. I will focus on the recently-discovered Regulatory Switch (RS) phage, which reversibly excise and reintegrate into the bacterial chromosome to shift the host between different physiological states. I, and others, have shown that RS phages influence a wide variety of bacterial traits including sporulation, biofilm formation, mutation rates or bacteriocin production. However, we do not understand when, how or why these viruses cause such large changes to bacterial behavior. The goal of my project, therefore, is to understand how and why RS phage evolve as a new candidate model of parasite manipulation. Specifcally, I will answer: 1) When and how do RS phages alter host behavior? 2) What is the molecular basis for the effects of RS phage? 3) Why have RS phage evoved to change bacterial behaviours, and is there evidence of counter strategies in their bacterial hosts? I will work with the bacterium Bacillus subtilis, which is strongly affected by RS phage and a model organism, allowing me to employ the very latest molecular methods. My goal is to demonstrate that parasite manipulation is a major factor in the ecology and evolution of bacteria, whereby many bacteria are essentially puppets of their phage masters. Understanding how phage achieve this manipulation also has the potential for broad impacts in an era when the need to find new ways to control bacteria becomes ever greater.