Structural studies of the molecular systems that maintain and spread antibiotic resistance in bacteria by single particle cryo-electron microscopy
The extensive use of antimicrobial compounds over the past decades has led to the evolution and spread of antibiotic resistance against these compounds. This emergence and spread of resistance is increasingly becoming a global health crisis. Resistance against antibiotics are encoded by antibiotic resistance genes (ARGs) that are mostly harboured within extra chromosomal plasmid DNA. Plasmid borne resistance is on the rise as they provide the right platform for hijacking genes from the genome and spread them via horizontal gene transfer. A crucial process that guarantees the prevalence of these plasmids in the host cells is chromosome independent replication. Several clinically important plasmids replicate via an asymmetric replication process called the ‘rolling circle replication’ (RCR). Bacterial conjugation, the important means for the spread of resistance genes among bacteria also utilizes the RCR mechanism during conjugative DNA transfers.
The project aims are to biochemically capture the intermediates of these processes and to elucidate the near atomic structure of complexes using cutting-edge single particle cryo-electron microscopy. The structural studies will be supplemented by biophysical and biochemical analysis. This project will pave the path for rational drug design thus targeting the persistence and spread of antibiotic resistance genes among bacteria.
The proposed project will provide training in biochemical isolation and in vitro reconstitution of large macromolecular complexes, biophysical characterization of these complexes and in single particle cryo-EM workflow. This work will take advantage of the transmission electron microscopes at the NanoVision Centre located within Queen Mary and the state-of-the-art electron microscopy infrastructure at the Francis Crick Institute and Diamond Light Source.
The studentship will cover UK/EU tuition fees and provide an annual tax-free maintenance allowance for 3 years at the Research Council rate (£16,777 in 2018/19).
Applications are invited from candidates with, or expecting to be awarded, a degree (UK 1st or 2:1 or equivalent qualification) in a relevant area. A masters degree is desirable, but not essential, and relevant research experience may also be taken into account. Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our entry requirements for details: https://www.qmul.ac.uk/sbcs/postgraduate/phd-programmes/entry-requirements/
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FTE Category A staff submitted: 23.39
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