Advanced single-molecule biological physics tools to understand cellular complexity during division and DNA replication

Biological processes in living cells possess enormous complexity involving highly cooperative and coordinated effects between remarkable, nanoscopic molecular machines composed of individual protein molecule components.

The PhD student will work with Prof. Leake (http://single-molecule-biophysics.org/) co-hosted by the Departments of Physics and Biology at York, and Prof. Foster in the Dept of Molecular and Biology and Biotechnology at Sheffield, both of whom have outstanding international reputations in their respective fields of single-molecule biophysics and microbial cell biology. The project will apply new bespoke super-resolution optical microscopy methodologies to image multiple protein components simultaneously in single, living cells down to a precision of single molecules with a spatial precision of a few tens of nanometre and a millisecond temporal resolution, permitting the real-time observation of functional molecular machines across all spatial regions of single live cells [1, 2].

The project will study the coordination of cell division and DNA replication in bacteria as a system for developing new physical science techniques into an application area with direct relevance to understanding the action of antibiotics [3]. The work will be highly interfacial using existing and newly developed fluorescent protein labelled strains in which key cell division components have been tagged in live Staphylococcus aureus cells. This pathogen is notorious as the antibiotic resistant ‘super-bug’ MRSA/VRSA. The tagged bacteria will be analysed using novel multi-colour and multi-polarization high-speed fluorescence imaging in living cells at the single-molecule level, under conditions of both normal and impaired DNA replication. This will take the bespoke optical microscopy into a new ‘multi-dimensional’ regime, addressing fundamental biological questions, which are essentially intractable using other methods.

3-year PhD studentships with EPSRC minimum stipend of £13,726 p.a.* are available. EU and overseas students are also encouraged to apply. [ *N.B., this is the 2013/14 minimum EPSRC stipend rate. Subject to annual adjustment. ]

This project forms part of a new White Rose studentship network ‘New single molecule techniques for understanding the physics of living systems’ and is made up of a team of collaborators from the Universities of Sheffield, Leeds and York. The goal of the network is to develop new physical approaches to answer biological questions and new ways for working collaboratively across the physics-life science interface to maximise the impact of these approaches.

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