Novel microfluidic technologies to interrogate bacterial pathogens with single-cell precision, Biosciences – MPhil/PhD (Funded

The University of Exeter’s College of Life and Environmental Sciences, in partnership with Defence Science and Technology Laboratory (DSTL), is inviting applications for a fully-funded PhD studentship to commence in January 2018 or as soon as possible thereafter. This studentship is only available to UK nationals. For eligible students the studentship will cover tuition fees plus an annual tax-free stipend of at least £14,553 for 4 years full-time, or pro rata for part-time study. The student would be based in the Living Systems Institute at the Streatham Campus in Exeter and must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree in one of the following areas: Biosciences, Biochemistry, Chemistry, Physics or Engineering.

The use of microfluidic devices has recently allowed us to recognise that isogenic microbial populations contain substantial cell-to-cell differences in gene expression (Tanouchi et al., 2015 Nature 523:357) and growth rate (Wang et al., 2010 Curr. Biol. 20:1099). However, the cell-to-cell differences in the response of pathogens, to physical, chemical or environmental stresses remain to be established. Scrutiny of bacterial phenotypes at this level of detail is of particular relevance for pathogens, where the infectious dose can be very low (1-10 bacteria) and some persistent and viable but non-culturable phenotypes can survive for long periods of time in the environment.

This project will fill this gap in our knowledge by bringing together extensive expertise and experience in microscopy and microfluidic systems available in Dr Stefano Pagliara group at Exeter and expertise in the handling and manipulation of dangerous pathogens available at Dstl. The successful candidate will develop miniaturised devices for the isolation, manipulation and study of thousands of single bacteria including biological warfare agents. Bacteria will be organised in two geometries: linear microcolonies (Wang et al., 2010 Curr. Biol. 20:1099) and biofilms (Kim et al., 2012 Lab Chip 12:1157), the latter permitting to evaluate decontamination efficiencies. The student will firstly optimise microfluidic and imaging protocols on the experimentally tractable Escherichia coli model system and then adapt them to study pathogens such as Bacillus anthracis UM23, Burkholderia thailandensis, Francisella tularensis LVS and Coxiella burnetii strain Phase 2. This will allow evaluation of heterogeneity in the response to environmental stressors such as heat, nutrient depletion and antibiotic exposure.

The scientific outcome of this project will be the development of tools to enable an increased understanding, on a single-cell level, of the fundamental biology of bacteria in response to external single or multiple stresses, such as antibiotics or a combination of nutrient limitation and drug exposure. This information will expand our capability to treat pathogenic and biological warfare agent infections and it will also underpin several other research areas such as animal model development and the identification of novel antimicrobial targets. Information regarding the variability within bacterial populations will also likely inform other areas of importance such as detection and diagnostics. As such, this ground-breaking technology has the potential for broad and significant impact in all engineering, biological, pharmaceutical and medical research focussed on the evaluation of environmental stressors on the different phenotypes within a population of pathogenic bacteria.

If you have any general enquiries email [Email Address Removed] or phone +44 (0)1392 725150/723706. Project-specific queries to, Dr Stefano Pagliara, [Email Address Removed]