Chromatin Immunoprecipitation-DNA sequencing (ChIP-seq) aiming to identify genes regulated by the bZIP ZipD transcription factor in Aspergillus fumigatus

• Grant number: 17/07732-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: August 14, 2017
• End date: August 13, 2018
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Patrícia Alves de Castro Silva
• Supervisor: Thomas Mitchell
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Ohio State University, Columbus, United States
• Associated to the scholarship: 16/12948-7 - The role of mitogen-activated protein kinase (MPKA) MpkA in regulating gliotoxin production in Aspergillus fumigatus., BP.PD

Abstract

Aspergillus fumigatus is a major opportunistic pathogen and allergen of mammals. Calcium signaling is essential for A. fumigatus pathogenicity and is regulated by the CrzA transcription factor. The increasing number of fungal infections resistant to drugs corresponds to a challenge for the treatment of these opportunistic infections in immunocompromised patients. In this sense, the highly conserved fungal stress response pathways could represent potential targets for the development of new therapies. Previously, studies of our laboratory revealed the ZipD transcriptional factor, encoded by the gene zipD (Afu2g03280), was up-regulated in the presence of calcium and the deletion of zipD resulted in increased sensitivity to high levels of calcium and caspofungin. The data obtained until now suggest that this gene may play an important role in calcium signal transduction mechanisms. Thus, the characterization of the target genes regulated by ZipD using Chromatin Immunoprecipitation - DNA sequencing, upon exposure to calcium stress, could provided an excellent opportunity to identify genes and pathways that are under the influence of zipD and its involvement with calcineurin/CrzA pathway, as well as a better understanding of the role of ZipD in A. fumigatus, providing useful information for potential antifungal therapies, like antifungal combinatorial treatment, potentially attractive and more efficient to avoid the emergence of drug resistance in clinical isolates.