Cell-to-Cell Variability in Chemotactic Signal Integration

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Project Summary Cell-to-cell variability in gene expression and stochasticity in biochemical reactions allow a single genotype to generate many different phenotypes. This non-genetic diversity has relevant medical implications since it leads to antibiotic persistence in pathogenic bacteria and may enhance virulence behaviors. Thus, understanding the role of cell-to-cell variability in the behavior of microbial populations is of critical clinical importance. The proposed work will determine how bacterial populations utilize cell-to-cell variability to process complex environmental signals. Specifically, we will learn how the adaptation machinery of the highly conserved bacterial chemotaxis network allows populations to modulate cell-to-cell variability in sensitivity to different stimuli when background signals are present. Then, we will learn how preferential detection of different chemoeffectors varies in bacterial populations, and whether populations divide signaling labor to detect and respond to stimulus mixtures. These questions will be answered using a novel microfluidic device developed in our lab which can apply fast- switching stimuli to cell populations. Responses to chemotactic stimuli will be determined with a well-established FRET reporter system which was recently further developed for use in single- cell measurements. With our extensive quantitative expertise, we will use our measurements to constrain a mathematical model of how cell-to-cell variability affects signal processing by populations, and how diverse populations process signals differently from single cells.