Investigating the structure and function of the divisome, the multi-protein complex that facilitates cell division in bacteria.
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When bacteria and archaea divide most form a ring structure that facilitates the separation of the mother cell into two daughter cells. The best-known component of the cytokinetic ring is FtsZ protein, the bacterial tubulin homologue. FtsZ polymers guide the assembly of a large number of downstream proteins that collectively form the divisome, the complex that synchronises events that have to take place for daughter cell separation. For example, constriction of the inner membrane needs to be coordinated with changes in the cell wall and outer membrane, in cells where those exist. Our aim is the mechanistic understanding of the divisome, how its various components work together and how it is assembled.
In the past, we have worked on many aspects of this problem but we would now like to utilise the power of new methods in electron cryomicroscopy (cryoEM) that enable the interpretation of the data with atomic models, directly leading to mechanistic insights. For this it is planned to assemble large sub-complexes of the divisome by protein co-expression methods in bacteria and subsequent mild isolation in order to obtain meaningful samples for cryoEM investigation.
It may then become possible to combine these data with volumes extracted from cellular electron tomograms, showing the divisome in their normal cellular environment, bridging the gap between structural and cell biology.
Prokaryotic cell biology is a new exciting field because it is thought to be possible to provide complete atomic descriptions of phenomena that in eukaryotes have eluded this goal because of their complexity, such as cell division, cell shape changes, motility, chemotaxis, chromosome segregation and many more.
The project will include many molecular biology techniques as well as protein purification, electron cryomicroscopy and the unique opportunity to learn electron cryotomography (cryoET) of bacterial cells.
Szwedziak, P. and Löwe J. (2013)
Do the divisome and elongasome share a common evolutionary past?
Current Opinion in Microbiology 16, 745-751
Szwedziak P., Wang Q., Bharat T.A.M., Tsim M. and Löwe J. (2014)
Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division
eLife 4, 10.7554/eLife.04601
Duggin I. G., Aylett C. H. S., Walsh J. C., Michie K. A., Wang Q., Turnbull L., Dawson E. M., Harry E. J., Whitchurch C. B., Amos L. A. and Löwe J. (2014)
CetZ tubulin-like proteins control archaeal cell shape
Nature 519, 362
Bharat T.A.M., Murshudov G.N., Sachse C., Löwe J. (2015)
Structures of actin-like ParM filaments reveal the architecture of plasmid-segregating bipolar spindles
Nature 523, 106