Species from several fungal genera, including Candida, Aspergillus, Pneumocystis and Cryptococuss have the potential to give rise to serious clinical infections and are estimated to cause 1.5 million deaths per year. Despite their importance as human pathogens, our understanding of how they affect immune cells, and how this might be affected by the presence of other pathogens is incomplete.
Advances in mass spectrometry have made it possible to look at changes in the total and phospho proteomes in cells. Using these techniques, the changes induced by infection by Candida albicans alone or in combination with Pseudomonas aeruginosa will be examined in iPS derived human macrophages. Pseudomonas is a common pathogen in the lungs of cystic fibrosis patients and co-infection with Candida has been linked to a worse clinical outcome. The proteomic data will be used to map novel signalling networks induced in the macrophages and the functional significance of selected components of these networks investigated via generating knockouts via CRISPR/Cas9 mediated technology.