PhD Studentship: Developing microfluidic platforms to fight infectious diseases and bio-threats
Click to apply Deadline: 26th June 2017

Project Description

This MRC funded project will screen for novel antimicrobial compounds in marine sediments and in soil by creating a miniaturised device to culture microorganisms in their natural environment. A similar macroscopic approach recently led to the discovery of teixobactin, a novel compound with potent antibiotic activity, in a soil field in Maine (Ling et al., 2015 Nature 517: 455 ). The principal supervisor (Dr Stefano Pagliara) has introduced a variety of novel microfluidic-microscopy approaches into his laboratory to grow, manipulate and characterise live cells (Pagliara et al., 2014 Nature Materials 13: 638 [PDF]; Otto et al., 2015 Nature Methods 12: 199 [PDF]).

This project will build on this expertise to design and fabricate microfluidic devices for growing microorganisms in their natural environments. You will use photolithography to produce silicon molds and replicate these devices in elastomeric materials to produce microfluidic chips. You will test the consistency of this novel approach by interfacing these devices with the microfluidic-microscopy platform at Exeter to confirm the reported antibiotic activity of known compounds extracted from soil microorganisms and will screen for novel compounds from marine samples taken from the coastal station L4, the marine station of Banylus-sur-Mer and from Thailand soil. You will work in the laboratories at the Defence Science and Technology Laboratory (Dstl, Porton Down), under the supervision of Dr Sarah Harding, where you will test novel isolated compounds with promising antibiotic activity against bacterial species relevant to bio-threat agents.

This project will open the way for the growth of previously unculturable microorganisms and the discovery of novel molecules with antibiotic activity against human pathogens thus helping our fight against infectious diseases and biothreats.

PhD Studentship: Novel microfluidic technologies to interrogate bacterial pathogens with single-cell precision
Click to apply Deadline: 24th July 2017

Project Description

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, 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 at Dstl. 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.