About This Project

Tiny fungal spores and yeast forms are found in the soil, air, and water. Infection takes hold when spores break dormancy and grow in or on us. Fungi kill more than 1.5 million people every year. The few existing antifungal drugs are becoming ineffective because of a dramatic increase in resistance. Deep sequencing of the spore transcriptome will help us understand the mechanisms regulating spore dormancy and identify new drug targets.

Ask the Scientists

What is the context of this research?

Aspergillus fumigatus is an opportunistic fungal pathogen found throughout the environment. This fungus makes large numbers of environmentally produced spores that get distributed by wind and water. It is estimated that the average person inhales ~ 100-300 spores daily.

Spores that are not cleared by the immune system are able to germinate and cause infection. The class of fungicides used to manage human disease are also used agriculturally. Increased use of agricultural fungicides is leading to increased drug resistance and a rise in mortality rates even with treatment (50-90%).

Spores are the source of infection, but much research focuses on resistance and management of infection once established. There is limited understanding of the spore biology.

What is the significance of this project?

Since germination is regulated by dormancy, it is important to understand how dormancy is established and maintained in the spore. Attempts at understanding have been done by comparing transcripts of spores to those of growing hyphae. Studies reveal that most transcripts in spores overlap with transcripts necessary for hyphal growth, making it difficult to identify which genes are essential for regulating dormancy.

We have identified sets of conditions resulting in low and high germination rates. By comparing the transcriptomes of spores raised under these different sets of conditions we hope to accurately parse out genes involved in regulating dormancy. If we can learn how dormancy is regulated we may be able to prevent spores from germinating and establishing infections.

What are the goals of the project?

RNA has been isolated and used to prepare libraries for Illumina high throughput sequencing. Instead of performing a low depth sequencing analysis traditionally done to identify differentially expressed genes we propose to perform a deep sequencing analysis.

By performing a deep sequencing analysis of Aspergillus fumigatus spore transcripts, we hope to identify genes with low expression levels that play crucial roles in regulating dormancy, for post-translational modifications that might otherwise be difficult to identify with conventional sequencing methods, and for other regulatory transcripts that may regulate dormancy.

Since regulation of dormancy is a well-conserved mechanism in fungi, we plan to follow up on genes that are well conserved across the kingdom.