Grant: Project Grant

Cryptococcus neoformans is an environmental fungus found throughout the world that causes serious disease of the lungs and brain in over one million humans each year. This pathogen is capable of infecting healthy humans and is particularly dangerous for those with weakened immune defences. Interestingly, only a minority of all individuals that are exposed to Cryptococcus neoformans will become ill. We believe that humans have natural differences that influence their susceptibility to severe cryptococcal infection and their response to treatment; however, we lack a firm understanding of the basic mechanisms that control these processes. Precise knowledge of host immune defense would be extremely valuable for diagnosis, prediction and monitoring of disease progression, and personalized therapy of cryptococcal infection. To identify the cellular and molecular mechanisms that control the development of severe cryptococcal disease, we use a mouse model of infection that closely resembles the human disease. We will apply cutting edge technology to analyze the function of lung cells, tissues, and organs and determine how the underlying cellular pathways and genes influence immunity. The knowledge we derive through this project will be translated into improved prevention and clinical management of serious human fungal infections.