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  Cryo-EM imaging of bacterial biofilm formation


   Sir William Dunn School of Pathology

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  Dr T Bharat  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Bacterial cells can aggregate on surfaces to form large multi-cellular communities called biofilms. Bacterial biofilms have a profound impact on human health because they are implicated in many diseases and infectious processes like cystic fibrosis and urinary tract infections. Structural biology of bacterial biofilm formation is poorly understood, and this is a relatively unexplored area of fundamental biology. The aim of the lab is to understand how different bacterial molecules orchestrate biofilm assembly at the cellular and multi-cellular level using high-resolution imaging coupled with structural biology techniques.

The DPhil project will involve characterization of key proteins mediating bacterial biofilm formation using state-of-the-art structural and cell biology techniques. This is an inter-disciplinary project, and we will provide training in microbiology, molecular biology, biochemistry, electron cryomicroscopy (cryo-EM) and associated image processing techniques. This project will also provide the student a unique opportunity to conduct high-resolution electron cryotomography (cryo-ET) of whole cells and to learn sub-tomogram averaging structure determination.

Depending on the experience and interests of the candidate, there will be flexibility to focus the project towards molecular cell biology, biochemistry or structural biology. Possible projects and further details will be discussed during the interviews

Funding Notes

4 Year DPhil Prize Studentships cover University and College fees, a stipend of ~£16,500 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. Minimum criteria are a relevant degree with at least a 2.1 or equivalent result and if English is not the first language, the standard English language test prior to admission. See http://www.path.ox.ac.uk/content/students for full details and to apply.

References

Bharat, T. A., Murshudov, G. N., Sachse, C., and Löwe, J. (2015) Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles. Nature 523, 106-110

Bharat, T. A., Russo, C. J., Löwe, J., Passmore, L. A., and Scheres, S. H. (2015) Advances in Single-Particle Electron Cryomicroscopy Structure Determination applied to Sub-tomogram Averaging. Structure 23, 1743-1753

Bharat, T. A., Castillo Menendez, L. R., Hagen, W. J., Lux, V., Igonet, S., Schorb, M., Schur, F. K., Kräusslich, H. G., and Briggs, J. A. (2014) Cryo-electron microscopy of tubular arrays of HIV-1 Gag resolves structures essential for immature virus assembly. Proc Natl Acad Sci U S A 111, 8233-8238

Bharat, T. A., Davey, N. E., Ulbrich, P., Riches, J. D., de Marco, A., Rumlova, M., Sachse, C., Ruml, T., and Briggs, J. A. (2012) Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy. Nature 487, 385-389

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