Identification of novel genes involved in stress response in Aspergillus fumigatus through quantitative barcode screening

• Grant number: 20/01131-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): September 01, 2020
• Effective date (End): August 31, 2021
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Gustavo Henrique Goldman
• Grantee: Clara Isabel Valero Fernández
• Supervisor: Michael John Bromley
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: University of Manchester, England
• Associated to the scholarship: 18/00715-3 - Molecular characterization of Aspergillus fumigatus transcription factors involved in calcium metabolism., BP.PD

Abstract

Invasive aspergillosis (IA) due to Aspergillus fumigatus causes extensive morbidity and mortality, especially among immunosuppressed patients. Very few classes of antifungal drugs are available for treating this disease and resistance is developing to first line therapeutics. New agents to treat IA are urgently required. When the fungus invades human lungs, it has to adapt to host environment in order to survive and deploy virulence strategies. In that context, those pathways involved in the adaption to external stresses have gained attention and some components have been suggested as potential antifungal targets. Classically, in vitro screening assays have been widely used to identify new antimicrobial drug targets. However, these assays are labour intensive and time consuming. To overcome these limitations, quantitative barcode screening has emerged as a new tool to identify novel drug targets reducing time and cost expenses. In this project, we propose to screen a genome wide knockout library of A. fumigatus to identify genes involved in adaptive responses to calcium and caspofungin stresses. In addition, we aim to use the same technology to establish the role of these adaptive responses to virulence and host-pathogen interactions. Ultimately, the data generated during this project will lead to the identification of components of stress response signalling pathways that could be promising antifungal targets and will be further characterized at the home laboratory. (AU)