Description
- Abstract:
- The pathogenic yeast Candida albicans can form multiple different cell types, including white cells and opaque cells, which help it to colonize different niches in the host. The transition between the white and opaque cell states is heritable and reversible. A network of transcription factor (TF) regulators governs white-opaque switching, including the conserved transcriptional repressor Ssn6. In an earlier study, we showed that several white-opaque TFs are capable of phase separation, and that this behavior is necessary for their function in regulating white-opaque switching. In this thesis, we examine the capacity of the transcriptional repressor Ssn6 to undergo phase separation, and dissect the protein into four domains: the N-terminal prion-like domain (N), the tetratricopeptide repeats (TPR), the medial prion-like domain (M), and the disordered C-terminal domain (CTD). Surprisingly, while we have shown that the prion-like domains of other white-opaque TFs are critical for function, deletion of either or both prion-like domains in Ssn6 had little impact on phase separation, cell type switching or gene expression. While the TPR has long been known to be critical for transcriptional repression, we now identify a key role for the previously unstudied CTD in mediating Ssn6 condensate liquidity, transcriptional regulation, and promotion of the opaque cell state. Understanding the phase separation behavior of this conserved transcriptional repressor is relevant to the field of Candida biology as well as to cell differentiation processes in higher eukaryotes.
- Notes:
- Thesis (Ph. D.)--Brown University, 2025
Citation
Dowell, Maureen,
"The role of phase separation in a transcriptional repression mechanism in Candida albicans"
(2025).
Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:jpc8j4wa/
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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations
Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department....