Cells sense changes in their environment and respond, often in an all-or-none fashion, modulating motility, growth, developmental fate, or synaptic efficacy. Bacterial chemotaxis is a pre-eminent model system for studies of sensory transduction, where mechanisms can be understood in atomic detail. E. coli is a nanotechnological marvel, with cells only a micron in size propelled by several helical filaments, each driven at its base by a rotary motor 50 nm in diameter powered by a proton flux. When the filaments spin counterclockwise (CCW), a cell moves steadily forward - it """"""""runs"""""""". When one or more filaments spin clockwise (CW), the cell changes course. A cell counts molecules of interest in its environment and extends runs deemed favorable. The counting is done by receptors that regulate the activity of a kinase that phosphorylates a response regulator that, when phosphorylated, diffuses across the cytoplasm and binds to the base of the flagellar motors, increasing the probability that they spin CW. Using fluorescence resonance energy transfer (FRET) between fluorescent fusion proteins in vivo, we will study receptor-receptor interactions responsible for high system gain, follow the diffusion of the response regulator within single cells, assess mechanisms for motor switching, and to try to learn whether there is feedback linking motors to receptors. We will test our understanding by computer modeling. New methods will be developed to probe motor function: to study proton-transfer in the high-speed limit, interactions of internal motor components, and behavior in an in vitro motor assay. Video analysis will be used to learn more about the motion of fluorescent flagellar filaments: how polymorphic transformations reorient the cell body, and how flagella on different cells interact to generate cooperative movement. While this effort is directly relevant to microbial virulence, it is meant as a study of fundamental biological processes: chemoreception, intracellular signaling, and conversion of chemiosmotic energy to mechanical work.
| Shrivastava, Abhishek; Patel, Visha K; Tang, Yisha et al. (2018) Cargo transport shapes the spatial organization of a microbial community. Proc Natl Acad Sci U S A 115:8633-8638 |
| Turner, Linda; Berg, Howard C (2018) Labeling Bacterial Flagella with Fluorescent Dyes. Methods Mol Biol 1729:71-76 |
| Hosu, Basarab G; Berg, Howard C (2018) CW and CCW Conformations of the E. coli Flagellar Motor C-Ring Evaluated by Fluorescence Anisotropy. Biophys J 114:641-649 |
| Ko, William; Lim, Sookkyung; Lee, Wanho et al. (2017) Modeling polymorphic transformation of rotating bacterial flagella in a viscous fluid. Phys Rev E 95:063106 |
| Hughes, Kelly T; Berg, Howard C (2017) The bacterium has landed. Science 358:446-447 |
| Berg, Howard C (2017) The flagellar motor adapts, optimizing bacterial behavior. Protein Sci 26:1249-1251 |
| Lele, Pushkar P; Roland, Thibault; Shrivastava, Abhishek et al. (2016) The flagellar motor of Caulobacter crescentus generates more torque when a cell swims backward. Nat Phys 12:175-178 |
| Turner, Linda; Ping, Liam; Neubauer, Marianna et al. (2016) Visualizing Flagella while Tracking Bacteria. Biophys J 111:630-639 |
| Hosu, Basarab G; Nathan, Vedavalli S J; Berg, Howard C (2016) Internal and external components of the bacterial flagellar motor rotate as a unit. Proc Natl Acad Sci U S A 113:4783-7 |
| Shrivastava, Abhishek; Roland, Thibault; Berg, Howard C (2016) The Screw-Like Movement of a Gliding Bacterium Is Powered by Spiral Motion of Cell-Surface Adhesins. Biophys J 111:1008-13 |
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