The role of the endoplasmic reticulum in viral and parasitic virulence

• Grant number: 21/14179-9
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: February 01, 2022
• End date: September 30, 2025
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Giuseppe Palmisano
• Grantee: Deivid Martins Santos
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications, AP.JP2
• Associated scholarship(s): 23/08586-6 - The PTMs crosstalk in lung epithelial cells during polarization and infection, BE.EP.DD

Abstract

The Endoplasmic Reticulum (ER) is a dynamic and multifunctional organelle, in which several essential cellular functions are developed including protein folding, protein glycosylation, redox balance, calcium storage and lipid and carbohydrate metabolism. ER homeostasis can be compromised by different biotic and abiotic factors and in order to re-establish homeostasis, the Unfolded Protein Response (UPR) is activated through three distinct pathways (IRE1±, PERK and ATF6), initiating a chain of reactions that can lead to a restoration of normal ER function or, in chronic cases of ER stress, autophagy and/or apoptosis. In the context of viral and parasitic infections, this work aims to study the role of the ER from two different points of view. The first will be through the study of ER-dependent (glyco)proteome and N-glycome of virulent (CL-Brener) and non-virulent (CL-14) T. cruzi strains, DTU VI, in different life cycle stages using a bottom-up mass spectrometry-based quantitative proteomics and immunoblotting. The second part will focus on the ER stress-UPR modulation during infections by SARS-CoV-2 WT and the Brazilian variants P.1 and P.2 in infected cells under different conditions through western blotting analysis. These results will shed lights on the role of T. cruzi glyosylation on parasitic virulence and the role of host ER stress during SARS-CoV-2 infection using different variants. (AU)

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)

MACEDO-DA-SILVA, JANAINA; ROSA-FERNANDES, LIVIA; GOMES, VINICIUS DE MORAIS; SANTIAGO, VERONICA FEIJOLI; SANTOS, DEIVID MARTINS; MOLNAR, CATARINA MARIA STANISCHESK; BARBOZA, BRUNO RAFAEL; DE SOUZA, EDMARCIA ELISA; MARQUES, RODOLFO FERREIRA; BOSCARDIN, SILVIA BEATRIZ; et al. Protein Arginylation Is Regulated during SARS-CoV-2 Infection. Viruses-Basel, v. 15, n. 2, p. 25-pg., 2023-02-01. (18/15549-1, 18/18257-1, 20/06409-1, 22/09915-0, 20/02988-7, 21/00140-3, 20/12277-0, 21/14179-9, 15/26722-8)

MULE, SIMON NGAO; ALEMAN, EVARISTO VILLALBA; ROSA-FERNANDES, LIVIA; SAAD, JOYCE S.; DE OLIVEIRA, GILBERTO SANTOS; MARTINS, DEIVID; ANGELI, CLAUDIA BLANES; BRANDT-ALMEIDA, DEBORAH; CORTEZ, MAURO; LARSEN, MARTIN ROSSEL; et al. Leishmaniinae: Evolutionary inferences based on protein expression profiles (PhyloQuant) congruent with phylogenetic relationships among Leishmania, Endotrypanum, Porcisia, Zelonia, Crithidia, and Leptomonas. PROTEOMICS, v. 24, n. 18, p. 17-pg., 2024-06-08. (21/14751-4, 16/23689-2, 20/04923-0, 18/18257-1, 18/15549-1, 17/04032-5, 20/13562-0, 21/14179-9, 18/13283-4)

GOMES, VINICIUS DE MORAIS; SANTOS, DEIVID MARTINS; MACEDO-DA-SILVA, JANAINA; LAZARI, LUCAS C.; MACHADO, RAFAEL RAHAL GUARAGNA; DOS SANTOS, ANCELY FERREIRA; ARAUJO, DANIELLE BASTOS; COUTINHO, JOAO VITOR PACCINI; ARINI, GABRIEL SANTOS; ANGELI, CLAUDIA B.; et al. P.1 and P.2 SARS-CoV-2 Brazilian variants activate the unfolded protein response with a time and pathway specificity. JOURNAL OF PROTEOMICS, v. 315, p. 17-pg., 2025-02-21. (20/06747-4, 16/04676-7, 15/26722-8, 19/09517-2, 22/13150-0, 21/14179-9, 20/06409-1, 18/15549-1, 18/07142-9, 18/18257-1, 17/24769-2, 16/20045-7, 20/04923-0, 21/00140-3)

FERREIRA, GRAZIELE CRISTINA; MANZATO, VERONICA DE MORAES; OKAMOTO, DEBORA NOMA; FERNANDES, LIVIA ROSA; SANTOS, DEIVID MARTINS; COSTA, GABRIEL CERQUEIRA ALVES; SILVA, FERNANDO ALLAN ABREU; TORQUATO, RICARDO JOSE SOARES; PALMISANO, GIUSEPPE; JULIANO, MARIA APARECIDA; et al. Sunflower Trypsin Monocyclic Inhibitor Selected for the Main Protease of SARS-CoV-2 by Phage Display. BIOLOGICAL & PHARMACEUTICAL BULLETIN, v. 47, n. 11, p. 10-pg., 2024-11-01. (20/05451-4, 20/04923-0, 18/18257-1, 19/03779-5, 18/15549-1, 20/02433-5, 12/03657-8, 21/12804-3, 21/14179-9)

BARBOZA, BRUNO RAFAEL; MACEDO-DA-SILVA, JANAINA; SILVA, LAYS ADRIANNE MENDONCA TRAJANO; DE MORAIS GOMES, VINICIUS; SANTOS, DEIVID MARTINS; MARQUES-NETO, ANTONIO MOREIRA; MULE, SIMON NGAO; ANGELI, CLAUDIA BLANES; BORSOI, JULIANA; MORAES, CAROLINA BORSOI; et al. ST8Sia2 polysialyltransferase protects against infection by Trypanosoma cruzi. PLoS Neglected Tropical Diseases, v. 18, n. 9, p. 33-pg., 2024-09-01. (22/00796-9, 21/14751-4, 20/04923-0, 18/18257-1, 21/00140-3, 18/15549-1, 20/02988-7, 22/09915-0, 21/00507-4, 23/02096-7, 21/14179-9)