Dissecting bacterial infection strategies at the single cell level

Mammals have central cellular defence systems that resist infection by a range of pathogens. These involve the NF-κB and STAT signalling systems, which we have shown to use dynamics and timing to encode pathogen-associated signals (Adamson et al. Nat Comms 2016 7:12057). We have recently developed novel tools to study the direct interaction of immune cells with relevant pathogens at the single cell level. These demonstrate that host cell and pathogen encounters are inherently dynamic and stochastic, leading to “seemingly” probabilistic infection outcomes in single cells. In particular we discovered that only a very small faction of the important food-borne bacterial pathogen Listeria monocytogenes could establish a successful infection of macrophages. This raises fundamental questions about the host and pathogen inputs that regulate the intracellular fate of Listeria in host cells, a key event in controlling infection.

The aim of the project is to develop new mechanical understanding of the of single cell host-pathogen interactions. In particular, the project will focus on the role of the NF-κB/STAT dynamics as well as microbial virulence systems in driving outcomes of Listeria infection in single and populations of host cells. The highlight is use of live-cell imaging and state-of-the-art single-cell genomics approaches to gain unique and exiting insights into the single cell infection process. The candidate will be joining an interdisciplinary group located in the Systems Microscopy Centre (http://www.systemsmicroscopycentre.manchester.ac.uk).

Training in novel and topical live-cell microscopy and single cell biology approaches will be provided to fit student’s interests and complement his/her existing skills.