Prof I Roberts, Prof Dave Thornton, Prof Richard Grencis
Applications accepted all year round
Self-Funded PhD Students Only
About the Project
Listeria monocytogenes is an intracellular food borne pathogen responsible for a number of life threatening infections. Following ingestion of contaminated food the bacteria invade via the gut mucosa before disseminating to the liver and spleen. To date little is know about the interaction between L. monocytogenes and host mucus that coats the GI-tract. This project will investigate the interaction between L. monocytogenes and the host mucus. First the project will use RNA-seq to study L. monocytogenes gene expression upon interaction with host mucus. Secondly, using this information, the project will generate defined mutants in L. monocytogenes and characterise their phenotype in response to interaction with, and navigation through, host mucus to reach target epithelial cells. Thirdly, the project will use biochemical approaches to monitor the effects of L. monocytogenes on the integrity of host mucus. Finally the project will investigate the effects on cytokine and chemokine production by epithelial cells following interaction between L. monocytogenes and host cell mucus. These experiments will generate vital information on this unstudied aspect of the life cycle of L. monocytogenes.
The project is interdisciplinary. Training will be provided in molecular microbiology, bioinformatics (analysis of RNA seq data), biochemical techniques to study mucus structure including analytical ultracentrifugation, agglutinin binding and immunology including ELISA and in situ hybridisation.
Funding Notes
Candidates are expected to hold (or be about to obtain) a first class class honours degree (or equivalent) in Microbiology/Biochemistry.
This project has a Band 2 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/).
Informal enquiries may be made directly to the primary supervisor.
References
Wang J, King JE, Goldrick M, Lowe M, Gertler FB, Roberts IS. (2015)
Lamellipodin Is Important for Cell-to-Cell Spread and Actin-Based Motility in Listeria monocytogenes. Infect Immun. 83:3740-8
Houlden, A., Hayes, K. S., Bancroft, A. J., Worthington, J. J., Wang, P., Grencis, R. K., Roberts, I. S. (2015)
Chronic Trichuris muris Infection in C57BL/6 Mice Causes Significant Changes in Host Microbiota and Metabolome: Effects reversed by pathogen clearance. PLoS One 10:e0125945
Corbett D, Goldrick M, Fernandes VE, Davidge K, Poole RK, Andrew PW, Cavet J, Roberts IS. (2017)
Listeria monocytogenes has both a bd-type and an aa3 -type terminal oxidase which allow growth in different oxygen levels and both are important in infection. Infect Immun. 2017 Aug 14. pii: IAI.00354-17. doi: 10.1128/IAI.00354-17. [Epub ahead of print]
Hasnain SZ et al., (2017).
Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion. PLoS Pathog 13(2):e1006218.