Project 458274

Fungi infect billions of people and kill at least 1.5 million people per year. Candida albicans is a leading human fungal pathogen that can cause life¬ threatening disease in immunocompromised individuals, with mortality rates of ~40%. Not only are there very few antifungal drugs available, but the CDC recently declared drug-resistant Candida species as a serious threat to human health. To combat this, a promising therapeutic approach is to target the fungal traits that help it to cause disease. One of these key virulence traits is the ability of C. albicans to switch from unicellular yeast to multicellular filaments when exposed to warm temperatures, such the human body experiencing fever. The goal of my research is to understand how C. albicans can sense elevated temperature and transduce this environmental cue through signaling pathways to enable filamentation. To accomplish this, I screened a mutant collection covering ~40% of the C. albicans genome and identified 40 genes required for filamentation in response to high temperature. Many of these genes are involved in processes related to actin organization and mRNA splicing, which suggests these cellular activities play a role in orchestrating high temperature induced filamentation. A collection of experiments including targeted mutations, protein-protein interaction assays, and RNA sequencing will be used to explore how filamentation is regulated by these biological processes. My project will identify the genetic mechanisms underlying the complex connection between temperature and C. albicans virulence, which could reveal new therapeutic strategies to cripple this life-threatening disease.