PhD Research Project: Host-pathogen interactions of the human fungal pathogen Cryptococcus neoforma
This project will investigate how the fungal pathogen Cryptococcus neoformans interacts with host cells (https://goo.gl/bJaQco). Cryptococcal infection is both a significant opportunistic infection that causes hundreds of thousands of deaths worldwide each year and an excellent opportunity to understand how pathogens avoid killing by the immune system.
Like many opportunistic pathogens Cryptococcus has not evolved specifically to avoid human immune cells. Rather, the normal environmental niche is soil, where its primary concern is capture by predatory amoeba. This project will therefore take a novel approach and use the amoeba Dictyostelium discoideum to investigate what happens to Cryptococcus within a physiologically revelant, model phagocytic cell. This provides an outstanding model system that allows us to genetically manipulate both the host and pathogen, and follow the transit of Cryptococcus through its host in great detail using time lapse fluorescence microscopy. This will allow the successful student to dissect how host and pathogen interact in greater detail than previously possible.
The primary aim of this study is to understand what happens to the human pathogen Cryptococcus neoformans after ingestion by phagocytic cells. This is the first line of defence in the immune system, and the ability of Cryptococcus to manipulate host phagocytes and evade digestion is the major cause of its pathogenicity (goo.gl/IkIf2V). Amazingly Cryptococcus is able to escape macrophages by a process called vomocytosis (goo.gl/BVKzL5). We have shown that Cryptococcus is also able to avoid being killed by Dictyostelium, as well as escape via vomocytosis.
This project with therefore use a combination of genetics, live cell imaging, biochemistry and flow cytometry to identify and characterize how Cryptococcus manipulates its host. This will provide a new level of understanding of cryptococcosis and identify new avenues for therapeutic intervention.
Applications from self-funded students or students with secured funding are also welcome.
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD Studentship, you must complete the University's application form using the following link: http://www.sheffield.ac.uk/bms/prospective_pg/how_to_apply
*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.
For informal enquiries about this project please contact either Dr. Jason King (Jason.King@Sheffield.ac.uk) or Dr. Simon Johnston (email@example.com)
Please see the King and Johnson lab websites for more details, and recent publications:
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