Cell populations often display substantial phenotypic diversity, even in homogeneous environments. At the same time, biological functions are not typically carried out by isolated cells, but rather by populations of varying functional abilities. The conflicts between phenotypic diversity and collective behavior have scarcely been examined. This project will address the gap in our understanding of these conflicts using Escherichia coli, a well-studied model system that exhibits both individuality and collective behavior. Groups of E. coli in a uniform field of nutrient form migrating bands mediated by the well-characterized chemotaxis system, which enables them to chase a gradient of nutrient generated by their consumption. However, single cells in an isogenic population of E. coli climb standing gradients with very different drift speeds, as recently characterized by the Emonet lab. How are these cells able to migrate together? We recently discovered a compensatory mechanism in which the fastest gradient-climbers localize to the front of the traveling band where the gradient is shallow, and the weakest performers localize to the back where the gradient is steep. But not all phenotypes are able to travel, indicating that collective migration can limit the amount of phenotypic diversity in the population. Here, I will examine the mechanisms by which bacteria resolve the conflicts between phenotypic diversity and collective behavior.
Aim 1 will determine how phenotypic diversity in the band shapes the traveling gradient of attractant, and how receptor adaptation together with the shape of the gradient in turn affect which phenotypes can travel. The results will produce a quantitative understanding of how bacteria use spatial organization to resolve the conflicts between phenotypic diversity and collective behavior.
Aim 2 will determine how differential growth and leakage of phenotypes off the back of the group affect collective migration. These studies will deepen our understanding of the extent to which growth can counteract the effects of collective behavior on population diversity.
Phenotypic diversity poses major medical challenges, permitting pathogenic microbes and cancer cells to outlast drug treatment and eventually develop permanent, drug-resistant mutations. It is unclear how phenotypic diversity is maintained during collective biological functions, such as neural crest migration or cancer metastasis. This project will investigate this question by studying collective migration of bacteria, which is mediated by the same core chemotaxis system that is important for pathogen infection and biofilm formation.
