The NIH (National Institute of General Medical Sciences) has awarded our lab an R35 MIRA grant to study the "Impact of ecological interactions on mutant fitness and evolution in microbes." This grant will support a major direction of our lab's research on how cross-feeding and competition for nutrients between microbes affect the fitness of new mutations, and ultimately the evolution of these populations.
Microbes acquire an enormous number of new mutations every day in nature, which enables them to rapidly adapt to environmental changes. At the same time, these microbes are often dependent on interactions between species and strains, especially the exchange of nutrients (cross-feeding). Our ability to predict evolution of microbes in different ecological environments is valuable for treating infectious diseases — for example, anticipating if and how fast a pathogen will evolve resistance to a treatment — as well as for designing personalized medicine based on an individual’s evolving microbiome. The overall goal of our lab's research is therefore to understand the feedback between these evolutionary and ecological processes in microbial communities.
A particular challenge in this field is our ability to quantitatively predict the effects of mutations on fitness, and how those effects vary across ecological environments. The distribution of fitness effects — the set of fitness values for all spontaneous mutations available to a population — is a key input to predicting how a population will evolve, and its variation across environments can reveal unknown gene functions. However, since we cannot empirically measure the fitness of mutations across all possible environments, it is crucial that we develop general principles for how mutant fitness changes across these environments to predict evolution. We need to know these rules, for example, to predict whether cross-feeding certain nutrients is likely to make a species adapt more slowly or more quickly, and how it changes the genes and molecular pathways under selection. In the next five years, our lab seeks to develop principles by which ecological interactions affect mutant fitness by addressing three questions:
Our work on this problem will contribute toward predicting microbial evolution across ecological environments as well as helping discover new functions of genes, especially secondary activities that arise under nutrient conditions not commonly tested in the lab.
