Bacterial Chemotaxis in Complex Dynamical Landscapes

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Chemical signals from a cell's environment can induce motion of that cell. This phenomenon, called chemotaxis, in the E. coli bacteria is one of the most extensively studied biological response. The E. coli chemotaxis network has become a paradigm for cellular behavior and signal transduction pathways and in this project the PI aims to understand signaling and behavior in E. coli considering them in the context of their function and the specific challenges they have evolved to address. The current experimental project is motivated by a recent theoretical work by the PI, which applies advanced tools of statistical physics to such biological problems. In the proposed experiments, a chemotaxis assay of a new type will be specially built to test those key predictions of the new theory. This project has the potential to change a widely accepted part of the paradigm of E.coli chemotaxis and possibly change the perspective on directed motion of other cells and organisms. The study synergistically combines theoretical analysis, innovative microfluidic technology, microbiology and molecular biology techniques, quantitative experiments with cells, and advanced microscopy and data analysis. The PI and Co-PI have complementary areas of expertise and have known each other for more than a decade from their previous work on mixing in chaotic and turbulent flows. Graduate students will be trained in cross-disciplinary environment and benefit from the synergism of the two groups involved in the proposed project with their complementary areas of expertise. The PIs will also continue to be involved in education, instruction and training that closely interface with the proposed work. The project is an experimental study of the role of adaptation in chemotaxis of Escherichia coli in different types of gradients of chemo-attractants and of adaptation in aerotaxis and pH-taxis of E. coli. A remarkable feature of E. coli chemotaxis is the perfect adaptation to changes in the concentration of aspartate, a commonly used attractant. The response of E. coli to a short-term change in aspartate concentration has asymmetric positive and negative lobes, with the integral equal to zero. The proposed experimental study is driven by a recent theoretical analysis by the PI, showing that the main advantage of the perfect adaptation is optimal navigation through environments with time-varying, complex spatial distributions of nutrients. Environments of this type are likely to be present in liquid E. coli cultures at the entry to the stationary phase, where E. coli motility is at its maximum. This analysis represents an alternative to a common narrative that the main function of the perfect adaptation is the retention of sensitivity to shallow gradients over a broad range of background concentrations. The theoretical predictions will be tested with a two-pronged experimental approach. First, chemotaxis of freely swimming wild-type and mutated E. coli will be studied in static linear profiles of attractants, for which the perfect adaptation is predicted to be non-optimal. Therefore, perfectly adapted E. coli are expected to have lower chemotactic efficiency than some of imperfectly adapted E. coli. Second, E. coli chemotaxis will be studied in a custom-built microfluidic device, which creates time-varying spatially non-uniform gradients of attractants. Based on the theory, the perfectly adapted E. coli are expected to outperform all competitors, securing highest average concentrations of the attractant along their swimming trajectories. The experiments will be facilitated by a technique recently developed by the PI that extracts temporal responses from trajectories of freely swimming cells. The proposed study will also apply this technique to the analysis directed motion of E. coli in well-defined gradients of oxygen and pH in a microfluidic device recently built by the Co-PI.