Investigating the evolutionary trajectories of P. aeruginosa

“Life will find a way….” In a now famous quote from the 1993 movie Jurassic Park, the “chaotician” Ian Malcolm nicely captures the essence of adaptation through evolution. But series evolutionary change often requires multiple mutations to arise – the changes arising from SNPs and indels in single genes usually amount to little more than phenotypic “tinkering”. So what would happen if we could “step on the evolutionary gas pedal” and accelerate the pace of change? Or alternatively, what would be the consequences of “slamming on the evolutionary brakes” to prevent adaptation? Well, these are just the kind of approaches that we have developed in the Welch lab, and we are applying these to look at how the opportunistic bacterial pathogen, Pseudomonas aeruginosa, adapts to the presence of infection-relevant selection pressures. Essentially, we’ve engineered the mismatch-repair system to come under the control of an inert chemical inducer, and so can “rheostatically” modulate the rate of mutation from very high (1000 x the wild-type level) to very low indeed (eliciting a state of “hypomutation” in which evolutionary change essentially grinds to a halt).

Using this system, we aim to investigate the evolutionary trajectories of P. aeruginosa when challenged with intense selection pressures e.g., in a polymicrobial environment, or upon exposure to antimicrobial agents or nutrient limitation. Project will involve elements of synthetic biology, microbiology, evolutionary biology, modelling and genomics. A stable polymicrobial culture system has recently been developed by the lab and is available for use.