Grant: Discovery Grants Program - Individual

Bacteria, viruses and other microbes adapt much more rapidly than humans. I use mathematical models to predict how quickly this microbial evolution unfolds. To do this, we need to predict which types of mutations might be beneficial to the organism, and how large their effects might be; this is called the ""distribution of selective effects"". Since many mutations, even if they are beneficial, are eventually lost from an evolving population, we would also like to predict whether new beneficial mutations will successfully spread through the microbial population, the ""fixation probability"". Finally, we would like to understand the ""adaptive walk"", that is, the process through which several beneficial mutations are acquired in sequence as the microbial population adapts to its environment.*Sophisticated mathematical treatments of each of these questions have been previously described in the literature. In particular, the fixation probability was first estimated, mathematically, nearly 90 years ago by some of the ""founding fathers"" of population genetics, but has never been tested. Although experimental techniques which could test these concepts have finally become available, recent work has demonstrated that our mathematical predictions must be precisely tailored to the organism and to the experimental protocol. Thus, quantitative experimental tests of these foundational quantities will only be possible after new mathematical predictions, specific for microbial populations, are developed. This is my research program.*The significance of understanding microbial adaptation is clear. The techniques developed here will be critical in predicting the rate of loss of microbial biodiversity, and the rate at which the microbiome will adapt to climate change. From a public health perspective, this work will also allow us to better predict the rate at which new pathogenic microbes will emerge, and the emergence of drug-resistance.*