Understanding the adaptability of Aspergillus fumigatus (360G-Wellcome-320833_Z_24_Z)

Serious fungal infections pose a unique challenge to human health, causing severe and life-threatening disease. Antifungal medications are essential for the treatment of fungal disease, but resistance is rapidly emerging across the globe. This is particularly concerning for Aspergillus fumigatus (Af) which is responsible for more deaths than any other fungal pathogen. Understanding the factors driving the remarkable adaptability of Af is essential for developing effective strategies to mitigate the risk of resistance emergence. Adaptability in Af is driven by multiple mechanisms including mutation, horizontal gene transfer and sexual reproduction. Here, I will investigate the contribution of each to understand how Af adapts to complex and changing environments by developing and implementing interdisciplinary tools. I will determine the interplay between mutator phenotypes, which I have recently identified, and stress in generating genetic diversity. Next, I will develop a new framework to understand hyphal fusion and horizontal genetic transfer in Af. Finally, I will map the polygenic and epistatic architecture of Af, explaining how Af adapts to complex multi-stress heterogenous environments. By unravelling the complex interplay of genetic and environmental factors that shape Af evolution, this research will provide critical information needed to combat the growing threat of drug-resistant fungal infections.