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RNA-binding proteins and hyphal mRNA transport in the pathogenic fungus Candida albicans

Project Summary

Candida albicans is a microscopic fungus that lives in human hosts. Although the presence of Candida cells does not affect the health of most human hosts, if the host’s immune system is compromised, C. albicans can cause a range of human diseases, from non-life threatening vaginal or oral infections to severe bloodstream and internal organ infections that are often fatal. The ability of C. albicans to switch growth forms between circular yeast cells and elongated hyphal cells is required for virulence in animal models, indicating the importance of studying all mechanisms involved in these transitions.

Hyphal cells form by directional growth at one end of a “mother” cell and hyphae contain a specific set of proteins required for invading host cells and tissues. Different models can explain how such proteins are found where they need to function. For example, some proteins may be made in the mother cell and then transported long distances into the hypha. A more efficient possibility, however, is that a messenger RNAs (mRNA) that contains the code that directs synthesis of a hyphal protein could be moved from the mother cell into the hypha, allowing local synthesis of multiple copies of the protein from a single mRNA, precisely where the protein is needed in the cell. Our long-term goal is therefore to understand how mRNAs are transported in C. albicans hyphae and how localized protein synthesis affects hyphal growth, function and virulence.

Our work focuses on an RNA-binding protein named Slr1, which is important for proper hyphal formation and which accelerates disease progression in an animal model of bloodstream infection. The objectives of this project are: 1) to test whether Slr1 cooperates with a protein known to transport mRNAs to the hypha and 2) to identify new proteins involved in hyphal mRNA transport that affect C. albicans hyphal formation and function.

Relevance of Research

With Candida infections having a mortality rate of up to 71% and the increasing resistance of Candida species to known antifungal chemotherapies, deepening our understanding of cellular processes that impact virulence is imperative. Our work will advance our fundamental understanding of mRNA transport mechanisms that can impact hyphal formation and function and therefore virulence of this pathogenic fungus. In addition, the undergraduate student researchers involved in the project will receive practical training and experience invaluable for future careers in biomedical sciences and medicine.