Abstract

The A. fumigatus genome contains 2 caspase genes, but their function is completely unknown. Since caspase-induced cell death in higher eukaryotes is a stress response that removes damaged cells for the benefit of the individual as a whole, our lab hypothesizes that caspases contribute to filamentous growth by allowing the organism to sacrifice nutrient-deprived or damaged hyphae for the benefit of the invasive growth of the colony periphery. In this project, the activity of two A. fumigatus caspases, CasA and CasB, will be measured in response to stress conditions, and their contribution to mycelial growth will be determined. The role of caspase activity to fungal growth in the host will be determined by testing mutants deleted for casA and casB for alterations in virulence, fungal burden or dissemination in a mouse infection model. The regulation of fungal caspase activity will be determined, focusing on levels of control that are well established for mammalian caspases, including caspase processing, intracellular localization and alternative splicing. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI064121-02
Application #
7069046
Study Section
Special Emphasis Panel (ZRG1-IDM-L (29))
Program Officer
Hernandez, Milton J
Project Start
2005-05-10
Project End
2010-05-09
Budget Start
2006-05-10
Budget End
2007-05-09
Support Year
2
Fiscal Year
2006
Total Cost
$31,197
Indirect Cost

  Institution

Name
University of Cincinnati
Department
Pathology
Type
Schools of Medicine
DUNS #
041064767
City
Cincinnati
State
OH
Country
United States
Zip Code
45221

  Publications

Feng, Xizhi; Krishnan, Karthik; Richie, Daryl L et al. (2011) HacA-independent functions of the ER stress sensor IreA synergize with the canonical UPR to influence virulence traits in Aspergillus fumigatus. PLoS Pathog 7:e1002330
Richie, Daryl L; Feng, Xizhi; Hartl, Lukas et al. (2011) The virulence of the opportunistic fungal pathogen Aspergillus fumigatus requires cooperation between the endoplasmic reticulum-associated degradation pathway (ERAD) and the unfolded protein response (UPR). Virulence 2:12-21
Richie, Daryl L; Hartl, Lukas; Aimanianda, Vishukumar et al. (2009) A role for the unfolded protein response (UPR) in virulence and antifungal susceptibility in Aspergillus fumigatus. PLoS Pathog 5:e1000258
Richie, Daryl L; Askew, David S (2008) Autophagy: a role in metal ion homeostasis? Autophagy 4:115-7
Richie, Daryl L; Fuller, Kevin K; Fortwendel, Jarrod et al. (2007) Unexpected link between metal ion deficiency and autophagy in Aspergillus fumigatus. Eukaryot Cell 6:2437-47
Richie, Daryl L; Miley, Michael D; Bhabhra, Ruchi et al. (2007) The Aspergillus fumigatus metacaspases CasA and CasB facilitate growth under conditions of endoplasmic reticulum stress. Mol Microbiol 63:591-604