# Evolutionary multispecies transcriptomics to reveal genes that govern fungal spore germination and pathogenesis

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $790,215

## Abstract

Project Summary
 Fungal pathogens of humans are prevalent in the environment, and commonly come into contact with hosts
via dispersal of vegetative spores. Although spore germination and subsequent development are recognized as
critical to the initiation of fungal-host interactions, little is known about the fungal genes that govern these events.
Our goal is to leverage comparative genomics, evolutionary biology and fungal pathogenesis to define genes
that are essential for spore germination, subsequent growth, and host colonization in an evolutionarily diverse
group of fungi. We have chosen fungi with a range of abilities to cause disease upon interaction of spores with
mammalian hosts, including primary, opportunistic, and nonpathogenic species. We will take advantage of a
highly effective and innovative pipeline that reveals genes whose evolving roles have led to phenotypic
differences among these species. PIs Trail and Townsend have defined a paradigm that brings together
comparative genomics, developmental biology, and transcriptomics into a single, unified phylogenetic framework
that will identify key genes that govern spore germination and outgrowth in these fungi. The linchpin of our
approach is use of the evolutionary relationship between the fungi to infer genes whose expression has been
altered during evolution from their ancestral state to each present-day lineage, thus allowing specific traits (such
as pathogenesis) to evolve. In our recently published work and preliminary data, this approach was immensely
powerful for identifying genes whose evolving role led to developmental and phenotypic differences among
species during (1) fungal sexual development and (2) spore germination and early infection during fungal
pathogenesis of plants.
 We will use a common medium to germinate spores from the following fungi: the primary pathogens
Histoplasma capsulatum and Coccidioides posadasii, the opportunistic pathogens Aspergillus fumigatus,
Fusarium oxysporum, and Chaetomium elatum, the infrequent opportunistic pathogen Aspergillus nidulans, and
the non-pathogenic Neurospora crassa. We will subject these fungi to transcriptomics over a time-course of
germination and subsequent development under temperature conditions relevant to germination in the
environment vs. in a mammalian host. We will reconstruct evolutionary changes of gene expression across these
multiple species to identify genes that have undergone recent shifts in gene expression, in particular shifts that
occurred along the shared ancestral branches where key traits (such as the ability to colonize mammals) have
evolved. These experiments will yield a high-confidence set of candidate genes whose function is expected to
be critical for spore germination and development in each organism. We will use gene knock-out technology to
interrogate the function of these candidate genes in spore germination and development. These studies will
identify potential targets for diagnostic, prophyl...

## Key facts

- **NIH application ID:** 9930045
- **Project number:** 5R01AI146584-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Anita Sil
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $790,215
- **Award type:** 5
- **Project period:** 2019-05-16 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930045

## Citation

> US National Institutes of Health, RePORTER application 9930045, Evolutionary multispecies transcriptomics to reveal genes that govern fungal spore germination and pathogenesis (5R01AI146584-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9930045. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*