Spatial organization of phenotypically diverse cells during collective migration

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PROJECT SUMMARY Cells within populations act collectively, allowing them to behave in ways that exceed the capability of a single cell. At the same time, even a genetically homogenous population exhibits phenotypic diversity, allowing the population to adapt in unpredictable environments. Both of these features complicate treatment of cancer, infections, and diseases. It is of critical importance to understand how phenotypic diversity modulates a population’s behaviors, yet this interaction is not fully understood. The proposed project will address this knowledge gap by studying the collective migration of commensal and pathogenic bacteria. Groups of bacteria (and eukaryotic cells) can migrate collectively by consuming attractants in the environment and chasing the moving gradient that they have created. This allows cell populations to travel over much longer distances than what can be achieved by an individual cell following external gradients. Our lab found that bacterial cells within migrating groups spatially organize themselves by their chemotaxis abilities, or the speeds at which they climb chemical gradients. This spatial organization within the migrating group allows cells with diverse motility behaviors to migrate together because it places high performers at the front, where the traveling gradient is shallower, and low performers near the back, where the traveling gradient is steeper. Here, I will examine the consequences of this spatial organization for populations that are migrating in different environments and performing pathogenesis. Aim 1 will determine how the spatial organization of motility behaviors in a bacterial population is altered when the physical properties of the environment are changed. Then, Aim 2 will explore to what extent a population of a human pathogen utilizes the spatial organization of secondary messenger levels and motility behaviors to co-sort virulence phenotypes. Our findings will be used to develop a mathematical model that describes how a migrating group of cells alters the spatial organization of its phenotypes to migrate across different environments. They will also provide insights on how the spatial organization of swimming behaviors can lead to co-organization of secondary messenger levels and virulence traits, allowing pathogens to perform multiple infection-related tasks simultaneously during migration. Because some of the basic mechanisms involved – e.g. phenotypic diversity in motility and the degradation or consumption of an external attractant to drive the collective behavior – are also present during the collective migration of immune cells and cancer cells, the findings in the project will be relevant beyond microbiology.