Postdoctoral Research Associate - Medical Research

A postdoctoral Research Associate is required immediately to carry out research in molecular simulation and multiscale modelling to investigate metalloenzymes involved in antibiotic resistance in Gram-negative bacterial pathogens.
Our targets are two metalloenzyme classes involved in resistance to key antibiotics used to treat infections by Gram-negative bacteria such as Escherichia coli or Pseudomonas aeruginosa. Zinc-dependent (metallo) beta-lactamases (MBLs) are hydrolytic enzymes that protect these organisms by degrading almost all classes of beta-lactam antibiotics, including the carbapenems- key agents in the treatment of healthcare-associated infections by multiresistant Gram-negative bacteria. The phosphoethanolamine transferase MCR-1 protects bacteria from the action of the polymyxin antibiotic colistin- the drug of last resort reserved for the most resistant pathogens- by modifying the lipid A component of the bacterial outer membrane. In both cases combinations of antibiotics (carbapenems or polymixins) with specific inhibitors of resistance enzymes may restore antibiotic susceptibility of producer organisms, enabling resistance to be overcome and prolonging the effective lifetime of available antibiotics.

The main aim of this project is to identify such inhibitors and characterize their interactions with their targets. The postholder will formulate, set up, perform and analyse molecular simulations, applying a range of molecular and biomolecular simulation tools (including in silico docking, density functional theory (DFT), molecular dynamics (MD), hybrid quantum mechanics/molecular mechanics (QM/MM) methods and QM calculations) specifically with the aim of investigating the interactions of these enzymes with substrates and inhibitors.

The post is supported for one year with funds from the US National Institutes of Health and the UK Medical Research Council. It will be housed in the School of Cellular and Molecular Medicine, although close interaction is required with collaborating researchers in the Schools of Biochemistry and Chemistry. The project would suit a recently qualified PhD. graduate with experience of in silico ligand discovery and/or molecular simulations. Applications from candidates with experience of multidisciplinary working are particularly encouraged. The project involves collaboration with experimental scientists within the Spencer group, at other UK Universities (Cardiff, Oxford) and with external institutions in the USA, Argentina, Uruguay and China.

Informal enquiries would be welcome to: Dr. J. Spencer (Jim.Spencer@bristol.ac.uk).

The closing date is midnight on Wednesday, 7 June 2017.

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