On the role of protein arginine methyltransferase 7 in Leishmania major infectivity and differentiation

• Grant number: 18/02761-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 01, 2018
• End date: November 30, 2018
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Juliana Alcoforado Diniz
• Supervisor: David Sacks
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: National Institutes of Health, Bethesda (NIH), United States
• Associated to the scholarship: 16/14657-0 - Methylation mediated by PRMT7 on the differentiation process of promastigotes into amastigotes and the parasite Leishmania major virulence, BP.PD

Abstract

Protein aRginine MethylTransferases (PRMTs) are important regulators of gene expression in Leishmania spp. These enzymes can target relevant regulatory elements at the posttranscriptional level, such as RNA binding proteins. Previous work in our laboratory has shown that PRMT7 in Leishmania major plays an important role in parasite virulence in vivo. Additionally, the fact that this enzyme is specifically expressed in the promastigote stage and its implication in pathogenesis suggests it may have a role in parasite differentiation. Preliminary results have shown that lesion size formation in the BALB/c mouse model can display drastically different profiles when using either a mixed stationary promastigote population or purified metacyclics for the in vivo infection. Interestingly, despite these distinctions, parasite burdens were comparable in all infections. Quantitative expression studies have also demonstrated that higher levels of PRMT7 are directly correlated to the expression of SHERP, known to contribute to metacyclogenesis in the sand fly. Together, we postulate that either an impaired development of procyclics into metacyclics may be modifying the efficiency of infection in mammals or that after entering the mammalian host the inflammatory response involves PRMT7-dependent regulatory elements. To address these hypotheses, it is necessary to evaluate parasite development within the sand fly vector and the infection profile in vivo in a murine system. To tackle these aspects of parasite development and host parasite interactions, we envisioned that David Sacks laboratory, at NIH/USA, would furnish the expertise necessary for both endeavours. The collaboration with David Sacks will permit a faster and robust track to achieve our central goals meaning the understanding of the contribution of PRMT7 toward Leishmania major differentiation, infectivity and pathology.

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)

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)