# Using Genetics and Genomics to Dissect Coccidioides Spherulation

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $208,667

## Abstract

Project Summary
Coccidioides spp. are major fungal pathogens endemic to Southern California, Arizona, Central America, and
South America. In recent years, the incidence of coccidioidomycosis has continued to rise, resulting in
hospitalization costs greater than $2 billion. Coccidioides infects, colonizes, and kills immunocompetent
individuals when they inhale spores from soils. The ability of Coccidioides to cause disease depends on an
elaborate developmental transition from saprophytic soil form to host form, which can be triggered in the
laboratory by incubating fungal spores at elevated temperature and carbon dioxide conditions. Specifically, the
hyphal form of the organism produces arthroconidia, which disperse easily and can be inhaled by mammalian
hosts. Once inside the host lung, arthroconidia germinate, enlarge, and undergo nuclear division and
segmentation to form large spherules filled with vegetative endospores. Rupture of the spherules allows
release of endospores and dissemination of the fungus to other sites.
Given the critical role of spherule development in disease progression, the focus of our proposal is the
genomic and genetic dissection of this process, also known as spherulation. We will take advantage of two
complementary approaches, high-resolution transcriptomics and genome-wide association studies (GWAS), to
perform an innovative molecular dissection of spherulation in Coccidioides. Principal Investigator Sil has
extensive experience working with Biosafety Level 3 pathogens and is well equipped to apply her expertise in
transcriptional profiling of thermally dimorphic fungi to Coccidioides. PI Brem is an evolutionary and statistical
geneticist with a track record of applying GWAS to fungi to identify genes that play a critical role in biologically
important traits. Together, we will harness the tools of systems genetics to discover new gene functions on a
genomic scale in Coccidioides. In Aim 1, we will identify a core set of spherulation-enriched transcripts by
performing a high-resolution time-course analysis of the transcriptome of three Coccidioides strains undergoing
spherulation. In Aim 2, we will apply GWAS analysis to identify genes that underlie variance of spherulation
phenotypes, using 150 clinical isolates of Coccidioides posadasii. Taken together, these approaches will
provide a rich dataset of spherulation-associated genes that will allow us to begin to elucidate critical molecular
events that take place during spherule development in the context of infection.

## Key facts

- **NIH application ID:** 9852989
- **Project number:** 5R21AI144855-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rachel Beth Brem
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $208,667
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852989

## Citation

> US National Institutes of Health, RePORTER application 9852989, Using Genetics and Genomics to Dissect Coccidioides Spherulation (5R21AI144855-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852989. Licensed CC0.

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