<mods:mods xmlns:mods="http://www.loc.gov/mods/v3" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-7.xsd"><mods:titleInfo><mods:title>Chromosome 1 Aneuploidy Regulates White–Opaque Switching in Candida albicans</mods:title></mods:titleInfo><mods:typeOfResource authority="primo">dissertations</mods:typeOfResource><mods:name type="personal"><mods:namePart>Maharjan, Kritika</mods:namePart><mods:role><mods:roleTerm type="text">creator</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Horrigan, Diana</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Cuomo, Christina</mods:namePart><mods:role><mods:roleTerm type="text">Reader</mods:roleTerm></mods:role></mods:name><mods:name type="personal"><mods:namePart>Bennett, Richard</mods:namePart><mods:role><mods:roleTerm type="text">Advisor</mods:roleTerm></mods:role></mods:name><mods:name type="corporate"><mods:namePart>Brown University. Biology and Medicine: Biotechnology</mods:namePart><mods:role><mods:roleTerm type="text">sponsor</mods:roleTerm></mods:role></mods:name><mods:originInfo><mods:copyrightDate>2026</mods:copyrightDate></mods:originInfo><mods:physicalDescription><mods:extent>, None p.</mods:extent><mods:digitalOrigin>born digital</mods:digitalOrigin></mods:physicalDescription><mods:note type="thesis">Thesis (Sc. M.)--Brown University, 2026</mods:note><mods:genre authority="aat">theses</mods:genre><mods:abstract>Candida albicans is a major human fungal pathogen capable of undergoing white-opaque phenotypic&#13;
switching, a stable, heritable, and reversible transition between two distinct cell states that influences&#13;
mating, host colonization, and immune evasion. The master transcriptional activator of the opaque&#13;
program, WOR1, resides on Chromosome 1 (Chr1), yet strains carrying three copies of Chr1 (trisomy)&#13;
show severely reduced switching frequencies, while loss of the extra Chr1 copy drives hyperswitching.&#13;
This observation suggests that dosage-sensitive repressors encoded on Chr1 outweigh the additional&#13;
WOR1 copy in the trisomic state, resulting in net suppression of switching.&#13;
To identify the chromosomal regions responsible for this suppression, fluorescent reporter strains carrying&#13;
mNeonGreen and mScarlet markers on distinct Chr1 homologs were engineered to enable live tracking of&#13;
Chr1 copy number. CRISPR/Cas9-mediated segmental deletions of four Chr1 regions (A, B, C, and D)&#13;
revealed that regions B and D harbor the dominant switching suppressors. Single deletions of either&#13;
region produced moderate increases in switching frequency, while their combined deletion in strain BD19&#13;
induced hyperswitching approaching that observed upon full Chr1 loss, without requiring deletion of&#13;
regions A or C. Heterozygous knockout of TUP1, a candidate repressor in region D, produced variable&#13;
switching outcomes attributable to spontaneous Chr1 arm loss rather than TUP1 dosage alone, consistent&#13;
with a distributed suppression model. Telomere-mediated chromosomal truncation is under development&#13;
to dissect the minimal suppressive sub-intervals within regions B and D at higher resolution. Together,&#13;
these findings demonstrate that Chr1 encodes a distributed network of dosage-sensitive repressors,&#13;
concentrated in regions B and D, that collectively set the transcriptional threshold for white-opaque&#13;
switching in C. albicans.</mods:abstract><mods:subject authority="fast" authorityURI="http://id.worldcat.org/fast" valueURI="http://id.worldcat.org/fast/00845627"><mods:topic>Candida albicans</mods:topic></mods:subject><mods:subject><mods:topic>White-opaque switching</mods:topic></mods:subject><mods:subject><mods:topic>Chromosomal aneuploidy</mods:topic></mods:subject><mods:language><mods:languageTerm authority="iso639-2b">English</mods:languageTerm></mods:language><mods:recordInfo><mods:recordContentSource authority="marcorg">RPB</mods:recordContentSource><mods:recordCreationDate encoding="iso8601">20260516</mods:recordCreationDate></mods:recordInfo></mods:mods>