Dr Gillian Fraser
Bacterial motility and flagella biogenesis
Pathogenic bacteria are often motile and their ability to swim through liquids and migrate over surfaces facilitates pathogen-host interactions and colonization of nutrient–rich environments. Many bacteria build complex nanomotors, called flagella, which rotate rapidly to drive swimming and swarming motility. We are investigating how these flagella are built. Specifically, we aim to uncover the molecular mechanisms underpinning flagellar type III export, focusing on the interactions between flagellar structural proteins and components of the membrane export apparatus. This project is co-directed by Colin Hughes.
Bacterial cell polarity
Bacteria are structurally complex and frequently display striking asymmetry. The bacterial cell poles are particularly specialised microenvironments, often enriched for structures such as signalling proteins, export machinery, adhesins, and flagella. Polarity is clearly seen in Vibrio cholerae, a highly motile pathogen that swims by rotating a single polar flagellum. During flagellum assembly, flagellar proteins are localised to the old cell division pole and exported from the cytosol via a dedicated type III protein export apparatus. Vibrio flagellum biogenesis seems to be tightly coupled to the cell division cycle, as each cell possesses only one flagellum. We are investigating Vibrio flagellum biogenesis as a tractable model to study the broadly significant themes of cell polarity, intracellular protein targeting and export, and the co-ordination of flagellum biogenesis and the cell cycle.
Bacterial nucleoid structure and gene expression
The bacterial nucleoid is a large dynamic structure containing DNA, RNA and proteins. To fit into the cell the nucleoid must be compacted extensively, and must fold in ways that allow genetic information to be replicated and transcribed. This is especially important in bacteria as their survival depends on their ability to adapt rapidly to the external environment by modulating gene expression and growth rate.
We aim to understand how the nucleoid folds and how this folding influences transcription. Nucleoid folding is orchestrated, in part, by specialized DNA-binding proteins called nucleoid associated proteins (NAPs). We have mapped the genomic binding sites of several NAPs - including Fis, HNS, IHF and HU - in the model bacterium E. coli K12. We have also determined the effects of NAP binding on both gene expression and genome-wide binding of RNA polymerase. We are now building on this work to study how NAPs influence long-range DNA interactions and the 3D structure of the nucleoid.