EASTBIO High throughput real time imaging of bacterial cells exposed to antibiotics

Our society is currently facing an important problem with the rise of multiple antibiotic resistant bacterial strains. As the development of new antibiotics has stalled in recent years, new strategies are urgently needed to supplement current available therapies. This involves increasing the efficiency of already available antibiotics as well as identifying new targets.

Antibiotics are increasingly used in combination to increase efficacy and limit emergence of resistance. Two important classes of clinically relevant antibiotics target bacteria by either inducing DNA damage or inhibiting cell well synthesis which ultimately leads to stopping bacterial cells growth and killing them. However, the relationship between the cellular physiology of bacteria and their susceptibility to antibiotics is not yet clearly understood. For example in certain growth conditions, treatment with a ribosome targeting antibiotics leads to better survival to a DNA damaging antibiotic. Thus, counter-intuitively, treatment with one antibiotic may lead to decreased efficacy of the second one. The reasons underlying this tolerance are not yet known but the magnitude of the effect depends on the growth conditions indicating that cell physiology plays an important role.

The objective of the project is to characterize experimentally and theoretically how the susceptibility of Escherichia coli cells to combination of various DNA damaging agents and protein synthesis inhibitors depends on the cells’ growth rate and other parameters of their physiology. Importantly, the project will largely involve the development of new cutting edge microscopy techniques to image cells in physiological conditions. Measurement will be performed at single cell level by combining a turbidostat system (to control growth rate) with automated microscopy. Subsequently, we will use a new imaging device that allows in situ imaging directly in the growth vessel thus avoiding any perturbation to cell physiology. The project will developped in close collaboration with Ogi Bio, https://www.ogibio.com, a newly formed start-up from the university of Edinburgh that are developing some of the growth vessels. The experimental results will be used to inform mathematical models of bacterial cell growth under combinations of antibiotics exposure.

Candidates with a background in physics, applied mathematics or quantitative biology interested in working in a highly interdisciplinary environment and keen to learn experimental biology and/or modeling are encouraged to apply.

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