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 lung, bone, and urinary tract infections. Structural biology of bacterial biofilm formation is poorly described, and this is a relatively unexplored area of fundamental biology. The aim of this project is to understand how different bacterial molecules are organized in the extra-cellular matrix of biofilms, forming a phase-separated environment protecting cells within biofilms from antibiotic treatment.
The DPhil project will involve studying bacterial biofilm formation using state-of-the-art structural and cell biology techniques. We will provide training in microbiology, molecular biology, biochemistry, and electron cryomicroscopy (cryo-EM). 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 ~£16,777 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See https://www.path.ox.ac.uk/content/prospective-graduate-students for full details and to apply.
References
Melia, C.E., Bharat, T.A.M. (2018) Locating macromolecules and determining structures inside bacterial cells using electron cryotomography. BBA - Proteins and Proteomics, 9, 973-981
Bharat, T.A.M., Hoffmann, P., Kukulski, W. (2018) Correlative microscopy of vitreous sections provides insights into BAR-domain organisation in situ. Structure, 26 (6), 879-886
Bharat T.A.M., et al (2017) Structure of the hexagonal surface layer on Caulobacter crescentus cells. Nature Microbiology, 2, 17059
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., et al (2012) Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy. Nature 487, 385-389
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