# Quantitative genetic approaches to Candida albicans oropharyngeal pathogenesis

> **NIH NIH F31** · OHIO STATE UNIVERSITY · 2021 · $36,526

## Abstract

Abstract:
 Candida albicans is a polymorphic commensal yeast that also manifests as a prevalent opportunistic
fungal pathogen. C. albicans infections manifest as oropharyngeal candidiasis (OPC), or thrush, in
immunocompromised individuals. Here, we deploy quantitative trait loci (QTL) analysis to identify genes
responsible for different forms of oral disease and to dissect regulatory networks governing the pathogenic
process of filamentation in C. albicans. These experiments will develop quantitative genetic approaches for all
parasexual Candida species.
 C. albicans has substantial phenotypic diversity among strains and is capable of residing stably in the
oral cavity or inducing epithelial damage that leads to either clearance by the immune system or OPC. However,
the genetic loci governing differences in these disease phenotypes between strains are not understood. To
address this, two isolates 529L and SC5314, a stable colonizer and damager, respectively, were mated to
generate parasexual progeny. Progeny genomes were sequenced at marker positions covering ~1% of the
genome. High rates of recombination during parasex facilitated mapping of 19 QTL regions associated with
epithelial damage phenotypes using a chromium release assay. Aim 1 will test specific loci from within those
QTLs to identify genetic determinants of damage and clearance by the immune system or non-damaging
persistence that differentiate strains. Furthermore, QTL analysis of filamentation will be performed, as hyphal
formation and host cell damage were separable phenotypes in some progeny.
 C. albicans uses filamentation to disrupt epithelial surfaces and progress into a disseminated systemic
infection. Current models of filamentation do not account for the substantial differences in filamentation among
C. albicans isolates. To identify species-wide regulators of filamentation, we will employ QTL techniques using
4 strains with distinct filamentation phenotypes in Aim 2. QTLs from all pairwise matings will uncover genes
regulating differences in filamentation phenotypes when grown on three different induction media at 30oC and
37oC to mimic the oral cavity and internal body temperature of the human host. Filamentation phenotyping will
be scored with a novel high-throughput visual analysis procedure. Thus, establishment of quantitative genetic
approaches in a parasexual species will greatly enhance identification of C. albicans pathogenesis regulators.
 My goal as a graduate student is to become a scientist whose research brings together multiple scientific
disciplines. While pursuing these aims, I will develop my skills at the bench and at the computer to bridge the
gap between informatics and biology, an increasingly important role in science. Throughout this project, I will
develop my communication skills by presenting this work to scientific audiences locally and internationally,
collaborating with other scientists, and writing my work for broader dissemination to the scien...

## Key facts

- **NIH application ID:** 10007581
- **Project number:** 5F31DE029409-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Robert John Fillinger
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,526
- **Award type:** 5
- **Project period:** 2020-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007581

## Citation

> US National Institutes of Health, RePORTER application 10007581, Quantitative genetic approaches to Candida albicans oropharyngeal pathogenesis (5F31DE029409-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10007581. Licensed CC0.

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