# Maturation, Germination, and Pathogenesis of Cryptococcus Spores

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2024 · $604,275

## Abstract

PROJECT SUMMARY/ABSTRACT
Worldwide, over a billion people each year experience high morbidity and/or mortality from the effects of
human fungal pathogens. People with AIDS, chemotherapy patients, and transplant recipients are at highest
risk of acquiring life-threatening infections, but many fungi also cause disease in apparently healthy individuals.
Among these is the spore-forming yeast, Cryptococcus, which is ubiquitous in the environment. Like many
pathogenic fungi, Cryptococcus causes disease when it is inhaled into the lung. From the lung Cryptococcus
can disseminate to the central nervous system (CNS) and cause fungal meningoencephalitis that is fatal ~25%
of the time, even with state-of-the-art treatments. In the United States the case mortality rate overall from
invasive fungal diseases is ~50%, indicating the dire need for improved therapeutic strategies. To develop new
antifungal therapeutics, we need to identify novel fungal-specific molecules or pathways. Thus, it is imperative
that we gain a better understanding of the fundamental biology of pathogenic fungi, especially the development
and growth of spores. Our long-term research goal is to understand how infectious spores survive in new
environments, including the mammalian lung, and use that information to identify fungal-specific targets for
therapeutic interventions. To accomplish this goal, we have developed the Cryptococcus system as a model
for the study of infectious spores. The objective of this proposed project is to determine the molecular
processes by which infectious spores transition into vegetatively growing yeast (germinate) and how this
process influences disease. Our overarching hypothesis is that determining the molecular mechanisms of
germination will identify key pathways in spore-mediated infections that can be targeted for inhibition. To test
this hypothesis, we will carry out three Specific Aims: 1) Determine the molecular pathways and processes
required for spore germination, 2) identify the molecular processes and events that promote germination
competence of spores, and 3) determine the effects of spore germination kinetics on host-pathogen
interactions and disease progression. We will combine molecular and classical genetics, gene expression
analyses, chemical genetics, protein composition analyses, and quantitative germination assays to reveal the
developmental and regulatory mechanisms that facilitate spore survival in diverse environments. At the same
time, we will use in vitro tissue culture models and a mouse intranasal model of infection to determine how
spores infect and escape the mammalian lung. These innovative experiments will result in an in-depth map of
spore pathways and insights into how spores invade the host. Understanding pathways and processes
associated with spore germination makes significant contributions to the long-term objective of this work to
identify new and diverse molecular targets that can be exploited for novel antifungal t...

## Key facts

- **NIH application ID:** 10779022
- **Project number:** 1R01AI179964-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** CHRISTINA M HULL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $604,275
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779022

## Citation

> US National Institutes of Health, RePORTER application 10779022, Maturation, Germination, and Pathogenesis of Cryptococcus Spores (1R01AI179964-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10779022. Licensed CC0.

---

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