How does the human fungal pathogen Cryptococcus neoformans avoid death by phagocytosis?

Supervisors: Dr Jason King (BMS) and Dr Simon Johnston (Infection and Immunity)

Application deadline: Friday 4 December 2015

Project Description:

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 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 it is ingested 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.

Key themes: Cell Biology / Development, Evolution, Genetics, Immunology, Medical/Clinical Science, Microbiology, Molecular Biology, Parasitology

Funding:

Competition-funded project (Students worldwide)

Contact details

Dr Jason King

Web: http://www.sheffield.ac.uk/bms/research/king

Email: Jason.King@Sheffield.ac.uk

Dr Simon Johnston

Web: http://www.sheffield.ac.uk/infectionandimmunity/staffprofiles/johnston

Email: s.a.johnston@sheffield.ac.uk

Further Information:

To apply formally for a PhD Studentship or Postgraduate Taught Course, you must complete the University's application form. See our 'How to Apply' page.