Copper homeostasis in fungal pathogenesis

The project will use Cryptococcus neoformans as a model system to explore copper (Cu) homeostasis in microbial physiology and pathogenesis. It will study the fungus's rapid cellular adaptations between high and low Cu states, particularly its Cu-resistant state during toxic Cu exposure in macrophages and its Cu-foraging state during Cu limitation in the central nervous system. A key focus is the Cuf1 transcription factor, the primary regulator of the cellular response to Cu levels. The research will build on prior work characterizing the Cuf1-dependent transcriptome to define conserved and novel mechanisms of eukaryotic copper biology. Specific aims include exploring the roles of Cu homeostasis and Cu-containing enzymes in cell wall/cell membrane function (SA1) and defining the impact of failed copper regulation on microbial pathogenesis (SA2).