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Molecular characterization of Aspergillus fumigatus genes related to endoplasmic reticulum regulated by transcription factor CrzA

Grant number: 12/07860-2
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): August 01, 2013
Effective date (End): September 30, 2013
Field of knowledge:Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
Principal Investigator:Gustavo Henrique Goldman
Grantee:Enyara Rezende Morais
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Aspergillus fumigatus is a saprophyte and opportunist fungus. Its reduced size conidia are easily able to reach the pulmonary alveoli through inhalation and cause several pathological conditions; pulmonary invasive aspergillosis is the most severe. The infection occurs when the compromised immune system fails to eradicate conidia in the lungs, allowing colonization, germination and eventual fungus penetration through the pulmonary epithelium to the bloodstream. In order to adapt to the various environmental stimuli, recognizing and signal transduction are of great importance to the fungus, since the signaling processes are also involved in pathogen-host interaction. The protein phosphatase calcineurin is an important connection mediator of calcium-dependent signaling to several cell responses in numerous organisms. Calcineurin acts, mainly, through activation of the transcription factor CRZ1 (Calcineurin Responsive Zinc Finger 1), homolog CrzA in A. fumigatus, through dephosphorylation of this factor leading to nuclear translocation. Calcineurin is known to be required for cell survival during several environment stresses; moreover genes related to the endoplasmic reticulum stress are regulated by this pathway. Due to efforts aiming to better understand the signaling pathway of calcineurin/CrzA in the laboratory supervised by Prof. Dr. Gustavo H. Goldman, there is a large amount of microarray hybridization data in vivo and in vitro for the mutant ”calA and ”crzA. These data associated to the chromatin immunoprecipitation assay followed by direct sequencing (ChIP-seq) of CrzA could supply a large basis for the identification of genes which show accumulation of mRNA modulated by CrzA. Therefore, the importance of this signaling pathway in the fungal physiology as well as its critical role in the disease induction makes this pathway and genes regulated by it an attractive target for antifungal drugs development. Thus, our objective is the functional characterization of genes related to the endoplasmic reticulum stress regulated by calcineurin-CrzA with the aim to expand the knowledge regarding this important signal transduction pathway as well as a better understanding about the CrzA role in A. fumigatus.

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