About the Project
http://www2.mrc-lmb.cam.ac.uk/groups/JYL/
When bacteria and archaea divide most form a ring structure that facilitates the separation of mother and daughter cells. The best-known component of the cytokinetic ring is FtsZ, the bacterial tubulin homologue. FtsZ polymers guide the assembly of a large number of downstream proteins that collectively form the divisome. The divisome complex 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 a 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 at medium resolutions. For this it is planned to assemble large sub-complexes of the divisome by protein co-expression methods in bacteria and eukaryotic systems and subsequent isolation in order to obtain 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 an exciting field because it is 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 (cryoEM) and the opportunity to learn electron cryotomography (cryoET) of bacterial cells.
References
Szwedziak, P., Löwe J., "Do the divisome and elongasome share a common evolutionary past?" Current Opinion in Microbiology 16, 745-51 (2013)
Szwedziak P., Wang Q., Bharat T.A.M., Tsim M., Löwe J., "Architecture of the ring formed by the tubulin homologue FtsZ in bacterial cell division", eLife 4, 10.7554/eLife.04601 (2014)
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., Löwe J., "CetZ tubulin-like proteins control archaeal cell shape", Nature 519, 362 (2014)
Bharat T.A.M., Murshudov G.N., Sachse C., Löwe J., "Structures of actin-like ParM filaments reveal the architecture of plasmid-segregating bipolar spindles", Nature 523, 106 (2015)
Bharat T.A.M., Kureisaite-Ciziene D., Hardy G., Yu E., Devant J., Hagen W.J.H., Brun Y., Briggs J.A.G., Löwe J., "Structure of the hexagonal surface layer on C. crescentus cells", Nature Microbiology 2:17059 (2017)
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