Studying the role of arginine methyltransferases in Leishmania braziliensis

• Grant number: 16/00969-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2016
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Lucas Bigolin Lorenzon
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/50219-9 - Studying the control of gene expression in Leishmania: post-translational modification, non coding RNAs, cis-elements and gene amplification, AP.TEM

Abstract

Parasites of Leishmania genus have been widely studied because of its importance in global health. The gene expression regulation in these organisms occurs mostly at post-transcriptional level. RNA biding proteins (RBPs) play several steps of this regulation. Recent studies showed that arginine methyltransferases (PRMTs) play some important roles in superior eukariotes and yeast, and among its targets there are several RBPs. Givem the importance of RBPs on post-transcriptional control, proteins which could modify and affect its interaction with RNA (PRMTs, in this particular case) become interesting targets to study in Leishmania spp. Our proposal is to study the effect of four arginine methyltransferases in Leishmania braziliensis. We are going to evaluate the expression profile of PRMT1, PRMT3, PRMT5 and PRMT6 in different development stages of the parasites (prociclic and metaciclic promastigotes, and axenic amastigotes). We are also going to investigate the phenotype of the parasites in response to altered expression levels of PRMTs (knockdown, knockout and overexpressor transfectants will be generated). Immunoprecipitation and mass spectrometry will be performed to identify proteins interacting with PRMTs. These interactions will be further studied, in order to better understand the biology of Leishmania braziliensis, a species of great importance on public health of Brazil.

Scientific publications

(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)

LORENZON, LUCAS; QUILLES JR, JOSE C.; CAMPAGNARO, GUSTAVO DANIEL; ORSINE, LISSUR AZEVEDO; ALMEIDA, LETICIA; VERAS, FLAVIO; MISERANI MAGALHAES, RUBENS DANIEL; DINIZ, JULIANA ALCOFORADO; FERREIRA, TIAGO RODRIGUES; CRUZ, ANGELA KAYSEL. Functional Study of Leishmania braziliensis Protein Arginine Methyltransferases (PRMTs) Reveals That PRMT1 and PRMT5 Are Required for Macrophage Infection. ACS INFECTIOUS DISEASES, v. 8, n. 3, p. 17-pg., 2022-03-11. (21/10043-5, 20/00088-9, 16/00969-0, 16/14657-0, 15/13618-8, 18/14398-0, 20/02372-6, 19/18607-5)

DINIZ, JULIANA ALCOFORADO; CHAVES, MARIANA M.; VASELEK, SLAVICA; MISERANI MAGALHAES, RUBENS D.; RICCI-AZEVEDO, RAFAEL; DE CARVALHO, RENAN V. H.; LORENZON, LUCAS B.; FERREIRA, TIAGO R.; ZAMBONI, DARIO; WALRAD, PEGINE B.; et al. Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. PLoS Neglected Tropical Diseases, v. 15, n. 3, MAR 2021. (19/18607-5, 16/14657-0, 18/02761-2, 17/02998-0, 15/13618-8, 16/00969-0)