The long term goal of this project is to investigate possible molecular strategies to control the detrimental effects of fungal pathogens on human health by targeting major regulatory genes that are unique to fungi. In this proposal the PI will focus on the human pathogen, Aspergillus fumigatus. Regulatory signaling genes tend to be conserved among fungal species. The PI's laboratory group has demonstrated that velvet, or veA, is a global regulatory gene that controls both morphological development and secondary metabolism in species of the genus Aspergillus, and across fungal genera in Fusarium spp. Interestingly, VeA has only been found in fungi. Aspergillus fumigatus has emerged as an important human pathogen with high mortality rates for the inmmunosuppressed. The fact that deletion of veA affects different cellular processes suggests that veA could also be a key factor in A. fumigatus multifactorial pathogenesis. The PI intends to explore the role veA in A. fumigatus by study veA-dependent compounds, particularly secondary metabolites, which may contribute to fungal disease. In this proposal, virulence of the veA mutant strains will also be directly assessed in a murine infection model. These basic studies will provide an essential foundation into the potential of VeA- targeting to control human pathogens.

Public Health Relevance

veA is a global regulatory gene unique to fungi that controls development and secondary metabolism in Aspergillus and other fungal genera. We will explore the role veA in the pathogenic A. fumigatus by studying veA-dependent compounds, such as secondary metabolites that may contribute to disease. The role of veA in virulence will also be directly assessed through murine infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
5R03AI079496-02
Application #
8238280
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
2011-03-15
Project End
2013-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
2
Fiscal Year
2012
Total Cost
$72,500
Indirect Cost
$22,500
Name
Northern Illinois University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001745512
City
De Kalb
State
IL
Country
United States
Zip Code
60115
Dhingra, Sourabh; Lind, Abigail L; Lin, Hsiao-Ching et al. (2013) The fumagillin gene cluster, an example of hundreds of genes under veA control in Aspergillus fumigatus. PLoS One 8:e77147