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Investigating novel treatments for sepsis by understanding the pathogenesis of invasive infection


Project Description

We have recently discovered that bacteria, previously considered extracellular pathogens replicate within a subset of macrophages before causing invasive infection (Ercoli et al., Nature Microbiology 2018). This work is now extended to pathogens relevant for zoonotic and veterinary infections in addition to work on human pathogens. The observations that many bacteria replicate in a hidden and protected nice prior disease is a game-changing observation as it may allow to design new treatment and prevention strategies which could have significant impact on health and wellbeing not only of humans but also of animals.

The work will address bacterial replication within the host, using ex vivo models and whole human organ perfusions (Chung et al., ALTEX 2018). This cutting-edge work on whole organs will be integrated with work on tissue cultures and primary cell cultures. Analysis will include confocal fluorescent microscopy, flow cytometry, and molecular methodologies. These approaches will require interdisciplinary training spanning from cell biology, microbiology, to next generation sequence analysis. In addition, the student will be introduced to methods necessary to perform the mathematical modelling of the bacterial fate during pathogenesis of infection.

The student will be integrated in a vibrant research group and we anticipate that the work will provide the student with a set of significant publications and a strong interdisciplinary training which should favour further academic work and employability.

For any further request of information please email the Pi MR Oggioni at for discussion of the project or to be put in contacts with the other PhD students of the group for further information.

Techniques that will be undertaken during the project

Biosafety level 2 microbiology techniques, cell culture, work on whole organs, organ slice cultures, confocal microscopy, flow cytometry and cell sorting, next generation sequencing and qPCR for gene expression analysis and mathematical modelling. These techniques map to multiple different fields spanning from Medicine, Animal work to Genetics, Cell Biology, Bioinformatics and Mathematics. Tis breath of work will give the student excellent interdisciplinary skills.

Available to UK/EU applicants only
Application information
https://www2.le.ac.uk/research-degrees/doctoral-training-partnerships/bbsrc

Funding Notes

4 year funded BBSRC Midlands Innovative Biosciences Training Partnership Studentship (MIBTP)
The funding provides a stipend at RCUK rates and UK/EU tuition fees for 4 years

References

1. Chung, W., Wanford, J., Kumar, R., Isherwood, J., Haigh, R., Oggioni, M., Dennison, A. and Ercoli, G. 2018. An ex vivo porcine spleen perfusion as a model of bacterial sepsis. ALTEX - Alternatives to animal experimentation. (Aug. 2018). DOI:https://doi.org/10.14573/altex.1805131.
2. Ercoli G, VE Fernandes, WY Chung, JJ Wanford, S Thomson, CD Bayliss, K Straatman, PR Crocker, A Dennison, L Martinez-Pomares, PW Andrew, ER Moxon, MR Oggioni. 2018. Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia. Nature Microbiology, 3(5):600-610. doi 10.1038/s41564-018-0147-1

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