Vacancies

If you are interested in joining the group there are a number of avenues that we could explore, please get in touch.

PhD studentship: Phage-antibiotic therapies. Apply

Bacterial infections are one of the leading causes of death worldwide and are estimated to lead to 300 million deaths by 2050. Antibiotics save millions of lives combatting infectious diseases. However, several bacteria, particularly those having a double membrane that makes them more impermeable, are resistant to antibiotic treatment. Therefore, we urgently need to develop strategies to overcome the current impasse by enhancing the uptake of antibiotics in bacteria or by using complementary tools for eradicating bacteria such as phage that are viruses targeting bacterial but not human cells (Lancet Infect Dis 19, 2, 2018). In order to understand the biological mechanisms underlying antibiotic and phage uptake in gram-negative bacteria, you will use a novel microfluidic technology that has recently been developed in Dr Pagliara team at the Living Systems Institute, University of Exeter (BMC Biol. 15, 121 2017; Lab on a Chip 20, 2765 2020). You will work in collaboration with the team of Dr Blaskovich at the University of Queensland, and Dr Van Houte at the Environment and Sustainability Institute, University of Exeter, to synthesise fluorescent derivatives of commonly used antibiotics and phage, respectively. Combined with a fluorescence microscope these microfluidic devices and fluorescent probes will allow you to measure antibiotics or phage entering or exiting individual bacteria as well as measuring the efficacy of these compounds in killing infecting bacteria. You will then apply mathematical models for analysing these data to understand how population heterogeneity detected in the single-cell data affects population and evolutionary dynamics. This work will be carried out under the supervision of Dr Ashby at the University of Bath and will allow to select potent phage and antibiotic combinations for the eradication of bacterial pathogens. This project also offers the possibility for collaboration visits to the National Physical Laboratory and the Defence Science and Technology Laboratory. Over the past ten years, single-microbe research has taken off around the globe engaging teams of scientists from different disciplines. As part of our battle against antibiotic resistance, by studying phage and antibiotic uptake in single bacteria your project will provide crucial novel knowledge for the development of new antibacterial therapies and a better use of existing ones.

PhD studentship: Uptake and toxicity of novel antibiotics. Apply

Antimicrobial resistance is recognized as a major global health threat, and treatment failures in patients with microbial infections are predicted to cause 10 million deaths annually by 2050. There is thus a desperate need to refresh the antibiotic development pipeline and develop new technologies to optimize antibiotic treatment. Infections caused by Gram-negative bacteria are of particular concern, due to the protection against antibiotics provided by the complex double-membrane cell envelopes of these organisms. This project aims to develop novel microfluidics and cytomics technologies to simultaneously investigate the uptake, efficacy and toxicity of both existing and novel antibiotics. In order to do this, you will use a novel microfluidic technology that has recently been developed in Dr Pagliara team at the Living Systems Institute, University of Exeter (BMC Biol. 15, 121 2017; Lab on a Chip 20, 2765 2020). You will work in collaboration with the team of Dr Blaskovich at the University of Queensland, and Dr Ben Housden at at the Living Systems Institute, to synthesise fluorescent derivatives of antibiotics and develop novel flow cytometry, respectively. The technology you will develop will represent a step-change in the way drug accumulation in bacteria and compound toxicity are studied, with potential benefits to the drug development and diagnostics industries, infectious disease specialists, as well as to the large academic community studying antibiotic transport in Gram-negative organisms.

PhD studentship: Ageing in microbes. Apply

Senescence, the accumulation of biomolecular damage leading to age‐related declines in reproduction and survival, is pervasive across the animal kingdom and has become a key focus of research in evolutionary biology and biomedicine. It has long been thought that unicellular organisms typically do not senesce, because without a clear germ soma divide any damage accumulated by one generation would be passed to the next, leading to the progressive deterioration and ultimate extinction of the lineage. However, the advent of high resolution live imaging techniques that allow researchers to track the life histories of individual cells and lineages within clonal E. coli populations has revealed evidence of clearly structured variation in both reproduction and survival among cells, which is now widely interpreted as evidence that bacteria do senesce (Stewart et al. 2005 PLOS Biology). This discovery has triggered a surge of interest in the possibility of bacterial senescence (MogerReischer & Lennon 2019 Nature Reviews Microbiology), both among evolutionary biologists and applied microbiologists. This project will combine cutting‐edge microbiology with experimental evolution to critically assess whether this complex phenotype in E. coli does indeed show the key mechanistic and evolutionary hallmarks of senescence. The project will have two main strands. First, as recent work has questioned whether the observed variation in performance actually does arise via damage accumulation (Lapinska et al. 2019 Philosophical Transactions of the Royal Society B), we will couple high resolution live‐imaging of dividing cell lineages with novel fluorescent markers that allow us to observe damage occurring in real time, to experimentally test whether the variation arises via damage accumulation or novel alternative mechanisms unrelated to senescence. Second, we will develop evolutionary models of microbial senescence, to investigate whether the true pattern of variation in cellular performance is consistent with what one would expect of senescence. We will then test the key predictions of these models by conducting experimental evolution using E. coli populations. This ambitious project is expected to significantly advance our understanding of senescence in microbes, shed new light on the evolutionary origin of senescence, and yield novel insights relevant to the global effort to combat antimicrobial resistance. The candidate will gain cutting‐edge research skills in senescence biology, microbiology, evolutionary modelling and experimental evolution, under the mentorship of a supervisory team with expertise in these areas. They will be based at Exeter renowned Penryn Campus in Cornwall, collaborating closely with colleagues at Exeter Streatham campus and in Bristol.