| Grant number: | 19/11929-7 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Start date: | November 01, 2019 |
| End date: | November 30, 2020 |
| Field of knowledge: | Biological Sciences - Microbiology - Biology and Physiology of Microorganisms |
| Principal Investigator: | Gustavo Henrique Goldman |
| Grantee: | Guilherme Thomaz Pereira Brancini |
| Host Institution: | Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
Abstract Aspergillus fumigatus is the most ubiquitous of fungi with airborne spores and inhaling of such structures can lead to Chronic Pulmonary Aspergillosis in immunocompromised individuals. The disease is a serious one and mortality can reach 100% if diagnosis is delayed. Essential to A. fumigatus survival both in decaying matter and in host tissues is the ability to sense the environment. G Protein-Coupled Receptors (GPCRs) are seven transmembrane domain proteins that are involved in response to external stimuli such as hormones, nutrients, protein, ions, and light. Upon activation, GPCRs change their conformation and trigger the dissociation between G± and the heterodimer G²³, each of which will act to activate or inhibit downstream signaling pathways. Because they are very important to cell signaling and are easily accessible at the cell surface, GPCRs are commonly used as drug targets. Indeed, an estimated 34% of all approved drugs target a GPCR. However, knowledge about fungal GPCRs is scarce, especially so for filamentous fungi. Only three of the 15 predicted A. fumigatus GPCRs have been characterized to date. Studying GPCRs can be difficult because the majority of gene deletion strains show no obvious phenotype. A previous screening of a library containing deletion mutants for all 15 predicted GPCRs revealed that the “gprJ strain produces a dark pigment when grown in liquid medium, thus indicating that it could regulate melanin production. The present research project proposes to characterize GprJ, including its role in growth, tolerance to different stressors, virulence, MAP Kinase signaling, global gene expression, and interacting partners. Our results will help in understanding how A. fumigatus senses its environment and will produce important knowledge about fungal GPCRs. (AU) | |
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