Epigenetic regulation of Leishmania gene expression

• Grant number: 20/00088-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: March 01, 2020
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Agreement: MRC, UKRI ; Newton Fund, with FAPESP as a partner institution in Brazil
• Principal Investigator: Angela Kaysel Cruz
• Grantee: José Carlos Quilles Junior
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL), AP.TEM
• Associated scholarship(s): 21/15182-3 - Monitoring processing, localisation and function of differentially expressed ncRNAs in Leishmania braziliensis by multi-colour RNA FISH on subcellular resolution, BE.EP.PD

Abstract

Control of gene expression in Leishmania occurs mainly at the post-transcriptional level. Central to the regulatory complexes are cis and trans-regulatory elements, mainly represented by mRNA elements (cis elements) and RNA binding proteins (RBPs), and may include hitherto unexplored content of noncoding transcripts (ncRNAs) recently detected in these parasites. We have previously demonstrated that ncRNAs appear to be a common feature of Leishmania transcripts, and approximately 300 putative ncRNAs were identified as differential expression (DE) transcripts. DE Leishmania braziliensis ncRNAs and RBPs interacting with them will be functionally investigated. State-of the-art technologies will be used for genome editing to generate knockout (KO) of ncRNAs DE in L. braziliensis and to endogenously tag these ncRNAs to evaluate phenotypic changes and identify interacting partners. The CRISPR/Cas9 system will be used for the KO of approximately one hundred small ncRNAs (transcripts of about 20-200 nucleotides) by associating this technology with a barcoding gene identification procedure. KO parasites for ncRNAs will be examined for their infection profiles capacity by in vitro infection assays. (AU)

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)