- Title Information
- Title
- Chromosome 1 Aneuploidy Regulates White–Opaque Switching in Candida albicans
- Type of Resource (primo)
- dissertations
- Name:
Personal
- Name Part
- Maharjan, Kritika
- Role
- Role Term:
Text
- creator
- Name:
Personal
- Name Part
- Horrigan, Diana
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Cuomo, Christina
- Role
- Role Term:
Text
- Reader
- Name:
Personal
- Name Part
- Bennett, Richard
- Role
- Role Term:
Text
- Advisor
- Name:
Corporate
- Name Part
- Brown University. Biology and Medicine: Biotechnology
- Role
- Role Term:
Text
- sponsor
- Origin Information
- Copyright Date
- 2026
- Physical Description
- Extent
- , None p.
- digitalOrigin
- born digital
- Note:
thesis
- Thesis (Sc. M.)--Brown University, 2026
- Genre (aat)
- theses
- Abstract
- Candida albicans is a major human fungal pathogen capable of undergoing white-opaque phenotypic
switching, a stable, heritable, and reversible transition between two distinct cell states that influences
mating, host colonization, and immune evasion. The master transcriptional activator of the opaque
program, WOR1, resides on Chromosome 1 (Chr1), yet strains carrying three copies of Chr1 (trisomy)
show severely reduced switching frequencies, while loss of the extra Chr1 copy drives hyperswitching.
This observation suggests that dosage-sensitive repressors encoded on Chr1 outweigh the additional
WOR1 copy in the trisomic state, resulting in net suppression of switching.
To identify the chromosomal regions responsible for this suppression, fluorescent reporter strains carrying
mNeonGreen and mScarlet markers on distinct Chr1 homologs were engineered to enable live tracking of
Chr1 copy number. CRISPR/Cas9-mediated segmental deletions of four Chr1 regions (A, B, C, and D)
revealed that regions B and D harbor the dominant switching suppressors. Single deletions of either
region produced moderate increases in switching frequency, while their combined deletion in strain BD19
induced hyperswitching approaching that observed upon full Chr1 loss, without requiring deletion of
regions A or C. Heterozygous knockout of TUP1, a candidate repressor in region D, produced variable
switching outcomes attributable to spontaneous Chr1 arm loss rather than TUP1 dosage alone, consistent
with a distributed suppression model. Telomere-mediated chromosomal truncation is under development
to dissect the minimal suppressive sub-intervals within regions B and D at higher resolution. Together,
these findings demonstrate that Chr1 encodes a distributed network of dosage-sensitive repressors,
concentrated in regions B and D, that collectively set the transcriptional threshold for white-opaque
switching in C. albicans.
- Subject (fast)
(authorityURI="http://id.worldcat.org/fast", valueURI="http://id.worldcat.org/fast/00845627")
- Topic
- Candida albicans
- Subject
- Topic
- White-opaque switching
- Subject
- Topic
- Chromosomal aneuploidy
- Language
- Language Term (ISO639-2B)
- English
- Record Information
- Record Content Source (marcorg)
- RPB
- Record Creation Date
(encoding="iso8601")
- 20260516