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  Probing the physical mechanisms of Bacillus subtilis cell division in living cells, one molecule at a time


   Institute for Cell and Molecular Biosciences

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  Dr S Holden  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

Do you want to join an exciting international collaboration to redefine our understanding of bacterial cell division by combining biophysics, bacterial cell biology, super-resolution microscopy and microtechnology?

- What scientific question will you investigate?
How does a bacterium divide? Not only is this one of the most basic questions we can ask about a living organism, but it is also important for medicine and biosciences, since bacterial cell division is a key antibiotic target. Bacteria divide by building a partition wall along the cell centreline against a high outwards pressure (up to 30 atmospheres!). To achieve this, the cytoskeletal protein “FtsZ” assembles a multi-protein division machine to insert cell wall material at mid-cell.

We recently dramatically improved our understanding of bacterial cell division machinery with our recent discovery (Bisson Filho et al, BioRxiv pre-print 2016)) that bacterial cell division in Bacillus subtilis is carried out by individual cell wall synthesis complexes, driven by the treadmilling motion of the bacterial cytoskeleton. You will work to further define the organization and dynamics of these dynamic synthesis complexes at the single molecule level in living cells, in partnership with a leading team of international collaborators (UK, USA, Netherlands). You will achieve this by applying cutting edge biophysical methods to a fundamental problem in bacterial cell biology: you will use single molecule super-resolution microscopy of live bacteria, combined with microfluidics and microtechnology, to directly observe the motion and organization of individual cell division proteins. This project will reveal for the first time the physical mechanism by which the bacterial cytoskeletal protein FtsZ and cell wall synthesis proteins coordinate their coupled motion.

- What will you be doing for your PhD research?
You will perform highly interdisciplinary work, working on both biophysics/ advanced microscopy and microbiology. This will include using super-resolution microscopy to measure the motion and stoichiometry of divisome proteins at the molecular level, microfluidic perturbation and microstructured immobilization of bacteria, quantitative data analysis, creation and genetic manipulation Bacillus subtilis strains containing fluorescently-labelled cell division proteins, and synthesis of new labelling probes for high resolution microscopy.

- What training will you receive?
You will join an exciting collaboration an exciting multidisciplinary international collaboration of biophysicists/ advanced microscopists (Newcastle, UK), bacterial cell biologists (Harvard, USA), biological chemists (Indiana, USA), nanotechnologists (Delft, Netherlands) and biochemists (Liverpool, UK). You will gain experience of each of these disciplines, with particular focus on “bacterial biophysics”, as well as nanotechnology, building on the key enabling technology which we developed between Newcastle and Delft, using microstructured immobilization to vertically orient bacteria for high resolution imaging.

- Is this project right for you?
We are seeking someone from either the physical or biological sciences with a strong interest in bridging the two disciplines and a good degree (BSc/MSci 2(1) or above, or MSc).


For further information see the website: http://www.ncl.ac.uk/camb/

To apply:
Please submit a full CV and covering letter directly to [Email Address Removed]


Funding Notes

This is a 4 year BBSRC studentship under the Newcastle-Liverpool-Durham DTP. The successful applicant will receive research costs, tuition fees and stipend (£14,296 for 2016-17). The PhD will start in October 2017. Applicants should have, or be expecting to receive, a 2.1 Hons degree (or equivalent) in a relevant subject. EU candidates must have been resident in the UK for 3 years in order to receive full support. There are 2 stages to the application process.

References

Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. AW Bisson-Filho, YP Hsu, GR Squyres, E Kuru, F Wu, C Jukes, C Dekker#, S Holden#, MS VanNieuwenhze#,3, YV Brun#, and EC Garner#. BioRxiv doi: 10.1101/077560 . Under review in Science. #Co-corresponding authors.