Cryptococcus neoformans is a fungus that is able to infect humans and cause serious disease. The nickel containing enzyme urease is essential for the ability of C. neoformans to survive within the lung and establish infection. Nickel has the potential to be toxic to the cell so that C. neoformans will have evolved mechanisms to acquire and distribute this metal ion in a way that does not cause cellular damage.
The objective of this proposal is to define the nickel homeostasic pathways of C. neoformans. Initially, genetic screens will be carried out to identify genes that are required for the acquisition, distribution and sensing of nickel in C. neoformans. The regulation of the identified genes and their respective gene products will be analysed using standard molecular techniques.
The cellular localisation of the relevant gene products will be identified and preliminary analysis of any nickel binding proteins carried out. This will establish C. neoformans as a model organism for the study of nickel metabolism as it relates to a fungal pathogen. This is a novel area of research that will provide the applicant with a biological system that will be the basis of his research for many years. Consequently, this proposal will help the applicant return to Europe from the United States and establish himself as an independent scientist.
This research falls within the life sciences, genomics and biotechnology thematic priority of the Specific Programme. In particular, this proposal provides a multidisciplinary approach to a basic biological process that has implications for human health.
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