Overcoming nutritional immunity: micronutrient acquisition mechanisms of pathogenic fungi. (360G-Wellcome-102549_Z_13_Z)

During infection, mammalian hosts restrict the availability of key micronutrients in a process called nutritional immunity. Pathogens, therefore, must possess specialised, high affinity micronutrient acquisition systems to grow in the human body and cause disease. The first aim of this project is to characterise the molecular mechanisms of micronutrient uptake and intracellular mobilisation in pathogenic fungi. I will identify these components using a combination of bioinformatics, transcriptomi cs and high throughput screening of mutant libraries. The phenotypes of C. albicans mutants lacking micronutrient scavengers will be examined. The second aim will be to assess the contribution of these genes to resisting host enforced nutritional immunity. This will be achieved by testing C. albicans mutants in defined cell culture infection models, tailored to mimic specific aspects of nutritional immunity. The third aim is to define the impact of micronutrient exploitation on the outcome of in fection. I will use animal models to elucidate the contribution of selected C. albicans genes towards commensal colonisation and invasive infection. Furthermore, I will use the information gathered in C. albicans to investigate the function of conserved components in other pathogenic fungi. This will validate whether the identified pathways represent broad-spectrum therapeutic targets.