Award details

Analysis of proteins regulating polar flagellum localisation and number in Vibrio cholerae

Reference	BB/D003733/1
Principal Investigator / Supervisor	Dr Gillian Fraser
Co-Investigators / Co-Supervisors
Institution	University of Cambridge
Department	Pathology
Funding type	Research
Value (£)	208,441
Status	Completed
Type	Research Grant
Start date	03/01/2006
End date	02/01/2009
Duration	36 months

Abstract

Flagellum-based motility is a key virulence factor of the pathogenic bacterium Vibrio cholerae. The flagellum is located at the old cell division pole, a specialised microenvironment that also houses the type II secretion apparatus that exports cholera toxin, other virulence proteins, and the CTXphi phage carrying the cholera toxin genes. V. cholerae builds only one flagellum per cell, suggesting that flagellum biogenesis must be closely coordinated with cell division. I aim to establish a project investigating the factors controlling polar localisation and flagellar number. The proposed work focuses on two V. cholerae flagellar proteins, FlhF and FlhG, that control flagellum localisation or couple flagellum biogenesis and cell division to ensure that each cell has a single polar flagellum. The flhF and flhG genes are conserved in several polar-flagellate pathogens, including Pseudomonas aeruginosa and Helicobacter pylori, and encode proteins with similarity to key effectors of membrane protein targeting (FtsY) and cell division (MinD), respectively. We will build on preliminary data using biochemical and molecular genetic techniques to establish the functions of these proteins and to identify interacting partners, thus mapping out the protein networks that coordinate flagellum biogenesis, polar targeting and cell division.

Summary

The bacterium Vibrio cholerae causes worldwide epidemics and pandemics of the severe diarrhoeal disease cholera. V. cholerae swims through liquids by rotating a long corkscrew-like propeller, called a flagellum, which is an important factor in the ability of the bacterium to colonise the human host and cause disease. The flagellum is positioned at one end, or pole, of the cell, as is the machinery that exports the major virulence factor cholera toxin. To ensure that each V. cholerae cell has a single flagellum at one pole, the cell must carefully regulate when and where this structure is built. I aim to establish a project that will address two questions: How is the flagellum specifically targeted to one cell pole? How is the number of flagella per cell regulated? I will build on preliminary work to determine the functions of two proteins, FlhF and FlhG, that target the flagellum to the right place in the cell and regulate flagellar number, respectively. Through our studies, we will build up a picture of the molecular networks that link flagellum biogenesis, cell asymmetry (or polarity), and cell division.

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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