Electron Tomography Cellular electron cryotomography allows the study of individual microbial cells in their native state and in three dimensions at macromolecular resolutions. Our experiments rely on highly sophisticated and specialized equipment. We have access to the electron microscopes at the NeCEN, the dutch cryo-electron microscopy center located in the Biology Institute of the Leiden University. The available instruments include 2 TITAN Krios microscopes with state-of-the-art equipment for highest quality data collection, as well as a fully equipped sample preparation laboratory. Bacterial Chemotaxis Nearly all motile prokaryotic cells utilize a highly sensitive and adaptable sensory system to detect changes in nutrient concentrations in the environment and guide their movements towards attractants and away from repellents. This chemosensory system allows the cells to selectively colonize preferential environments and is also involved in host infection by some pathogenic bacteria.The bacterial chemoreceptor array is a highly organized sensory patch composed of thousands of transmembrane receptor proteins. Attractants and repellents bind to the sensory domains of these receptors, thereby regulating activity of the histidine kinase CheA, which phosphorylates a soluble messenger protein. This messenger protein in turn diffuses through the cytoplasm to the flagellar basal body, where it modulates the direction of flagellar rotation.Chemoreceptor arrays are composed of trimers of receptor-dimers that are connected by rings of the histidine kinase and a linking protein, CheW. We are now working towards unraveling the structural changes that occur upon attractant binding, and understand the basis for the high cooperativity of the chemoreceptors in the array.Besides unraveling the detailed structure and function of the chemotaxis system in model organisms, we are interested in understanding their unexplored diversity across the bacteria and archaea, how they control bacterial behavior and how they are involved in pathogenicity.  

Electron cryotomography and bacterial chemotaxis. I am interested in understanding how microbes sense and respond to their environment. In order to gain insight into the structure and function of the molecular complexes involved in these behaviors, my lab uses electron cryotomography (ECT). This technique allows us to directly study microbes in their native state at resolutions capable of visualizing individual proteins.