Scholarship 14/15403-6 - Aspergillus nidulans, Retículo endoplasmático - BV FAPESP
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Aspergillus nidulans as a model to manipulate unfolded protein response-related genes

Grant number: 14/15403-6
Support Opportunities:Scholarships in Brazil - Doctorate
Start date until: November 01, 2014
End date until: July 31, 2018
Field of knowledge:Biological Sciences - Microbiology - Applied Microbiology
Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:André Ricardo de Lima Damasio
Grantee:Mariane Paludetti Zubieta
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:12/20549-4 - Secretion of heterologous glycoproteins in Aspergillus: effect of glycosylation pattern in functional parameters of glycosyl hydrolases, AP.BIOEN.JP
Associated scholarship(s):15/00660-6 - Deletion of genes related to the proteins secretion pathway in Aspergillus nidulans, BE.EP.DR

Abstract

In eukaryotes, unfolded protein response (UPR) upregulates genes responsible for restoring homeostasis in the endoplasmic reticulum (ER) during the incorrect accumulation of unfolded proteins. Homeostasis is restored due to activation of genes related to the secretory pathway such as those encoding chaperones and foldases, which increases the ER protein folding capacity. Some systems for heterologous proteins production have been developed by the over-expression of chaperones and foldases. However, the success rate with this strategy is low. Studies have shown that the constitutive UPR induction system in fungal strains have increased the production of proteins of interest. In Aspergillus, the transcription factor HACA is the central gene responsible for the activation of UPR. Furthermore, it is known that there is a cross talk between the UPR and the general amino acid control pathways, the latter being regulated by the transcription factor CPCA. Recently, a hypothesis suggested that this cross talk occurs through the formation of a stable heterodimer between HACA and CPCA that binds the promoter regions of genes involved in UPR, activating transcription. Therefore, the goal of this PhD project is, at first, obtaining strains of A. nidulans constitutively expressing HACA and CPCA genes and evaluates these strains for heterologous expression of target proteins. Furthermore, results will be obtained through global transcriptome analysis by RNA-seq of wild-type strains after induction of UPR by traditional drugs such as tunicamycin and dithiothreitol. This database will be important searching for new UPR targets to be manipulated for the purpose of obtain higher secretion of proteins of biotechnological interest, such as glycosyl hydrolases and accessory enzymes. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CONTESINI, FABIANO JARES; LIBERATO, MARCELO VIZONA; RUBIO, MARCELO VENTURA; CALZADO, FELIPE; ZUBIETA, MARIANE PALUDETTI; RIANO-PACHON, DIEGO MAURICIO; SQUINA, FABIO MARCIO; BRACHT, FABRICIO; SKAF, MUNIR S.; DAMASIO, ANDRE RICARDO. Structural and functional characterization of a highly secreted alpha-L-arabinofuranosidase (GH62) from Aspergillus nidulans grown on sugarcane bagasse. BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, v. 1865, n. 12, p. 1758-1769, . (13/08293-7, 12/20549-4, 14/04105-4, 14/15403-6, 13/24988-5, 14/23051-2, 08/58037-9)
RUBIO, MARCELO VENTURA; ZUBIETA, MARIANE PALUDETTI; LOURENO FRANCO CAIRO, JOAO PAULO; CALZADO, FELIPE; PAES LEME, ADRIANA FRANCO; SQUINA, FABIO MARCIO; PRADE, ROLF ALEXANDER; DE LIMA DAMASIO, ANDRE RICARDO. Mapping N-linked glycosylation of carbohydrate-active enzymes in the secretome of Aspergillus nidulans grown on lignocellulose. BIOTECHNOLOGY FOR BIOFUELS, v. 9, . (14/15403-6, 14/06923-6, 11/20977-3, 13/24988-5, 12/20549-4, 14/23051-2, 09/54067-3)
ZUBIETA, MARIANE P.; GERHARDT, JAQUELINE A.; RUBIO, MARCELO V.; TERRASAN, CESAR R. F.; PERSINOTI, GABRIELA F.; ANTONIEL, EVERTON P.; CONTESINI, FABIANO J.; PRADE, ROLF A.; DAMASIO, ANDRE. Improvement of homologous GH10 xylanase production by deletion of genes with predicted function in the Aspergillus nidulans secretion pathway. MICROBIAL BIOTECHNOLOGY, v. 13, n. 4, p. 9-pg., . (17/10083-1, 12/20549-4, 14/15403-6, 16/16306-0, 17/26315-9, 13/24988-5)
ZUBIETA, MARIANE P.; GERHARDT, JAQUELINE A.; RUBIO, MARCELO V.; TERRASAN, CESAR R. F.; PERSINOTI, GABRIELA F.; ANTONIEL, EVERTON P.; CONTESINI, FABIANO J.; PRADE, ROLF A.; DAMASIO, ANDRE. Improvement of homologous GH10 xylanase production by deletion of genes with predicted function in the Aspergillus nidulans secretion pathway. MICROBIAL BIOTECHNOLOGY, v. 13, n. 4, . (12/20549-4, 14/15403-6, 17/10083-1, 13/24988-5, 16/16306-0, 17/26315-9)
RUBIO, MARCELO VENTURA; FANCHINI TERRASAN, CESAR RAFAEL; CONTESINI, FABIANO JARES; ZUBIETA, MARIANE PALUDETTI; GERHARDT, JAQUELINE ALINE; OLIVEIRA, LEANDRO CRISTANTE; DE SOUZA SCHMIDT GONCALVES, ANY ELISA; ALMEIDA, FAUSTO; SMITH, BRADLEY JOSEPH; MARTINS FERREIRA DE SOUZA, GUSTAVO HENRIQUE; et al. Redesigning N-glycosylation sites in a GH3 beta-xylosidase improves the enzymatic efficiency. BIOTECHNOLOGY FOR BIOFUELS, v. 12, n. 1, . (12/20549-4, 13/08293-7, 16/16306-0, 17/22669-0, 17/10083-1, 19/00098-7, 14/15403-6, 13/24988-5)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
ZUBIETA, Mariane Paludetti. Aspergillus nidulans como modelo para manipulação de genes envolvidos no processo de unfolded protein response. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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