Award details

Bacterial Cell Division: Mechanisms and Regulation.

Reference	BB/C506613/1
Principal Investigator / Supervisor	Professor Jeffery Errington
Co-Investigators / Co-Supervisors
Institution	University of Oxford
Department	Sir William Dunn Sch of Pathology
Funding type	Research
Value (£)	1,476,920
Status	Completed
Type	Research Grant
Start date	01/10/2004
End date	30/04/2006
Duration	19 months

Abstract

Cell division is a fundamental process common to all living organisms. However, in no system is the process understood in molecular detail. This proposal describes a major programme aimed at trying to understand several aspects of cell division in a relatively simple organism, the bacterium Bacillus subtilis. This is an extremely tractable experimental system and one in which there is some prospect of understanding in molecular detail on a reasonable time scale. Division is governed by a tubulin homologue FtsZ which assembles into a ring-like structure at the site of impending division. About 10 other proteins associate with the ring to regulate its formation and help bring about constriction of the cell and synthesis of new cell wall and membrane. This proposal describes a 5 year program of research aimed at improving our understanding of various components of the division machinery. The proposal is divided into three themes. The first part concerns the early, cytosolic proteins involved in division, centred on FtsZ. We want to identify any remaining proteins involved in interactions with FtsZ and to define the network of interactions, with particular reference to the surface of FtsZ. We will use information on the network of interactions to facilitate biochemical reconstruction of the Z ring in vitro. If possible, we will try to exploit advances in imaging technology to improve our resolution of the structure of the Z ring in vivo. The second part concerns detailed characterisation of a new protein we have found that plays a key part in positioning the Z ring relative to the bacterial chromosome. It is responsible for a well-known effect in bacteria called nucleoid occlusion. The protein, Noc, will be analysed genetically and biochemically. It appears to have two separable functions: binding to the chromosome, and inhibition of the division machinery. We will try to reconstitute and characterise these activities in vitro. Finally, we will examine the role of thisprotein in a round pathogenic bacterium, Staphylococcus aureus (as opposed to the rod-shaped B. subtilis). The third theme concerns the late events of cell division, involving a set of transmembrane proteins required for synthesis of cell wall material in the division septum and possibly the membrane dynamics associated with division. We will characterise the last remaining protein of this group, FtsW and test its possible involvement in cell wall precursor synthesis. We will then investigate how the key player in cell wall synthesis during division, PBP 2B, is positioned and regulated by the FtsL, DivlB, DivlC and possibly FtsW proteins. We will then try to characterise the other facet of PBP 2B function by identifying the proteins that it interacts with to bring about wall synthesis. Finally, we will test the possible roles of the FtsL and DivlC proteins in membrane dynamics. Ultimately, this work should lead to a more complete understanding of the set of proteins responsible for cell division in B. subtilis and related bacteria. It should also take us some way towards reconstructing some of the key events of cell division in the test tube.

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
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

Associated awards:

BB/C506613/2 Bacterial Cell Division: Mechanisms and Regulation.

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