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Control of gene expression and genetlc plasticity in Leishmania


The present proposal aims at the use of comparative genomics and reverse genetics in the study of gene expression regulation and genetic plasticity in the protozoan parasite Leishmania. The proposed studies and approaches are in alignment with, and expand the projects that are being conducted in our laboratories (FAPESP Proc. 99/12403-3). We consider the investigation of occurrence and mode of action of ncRNAs in Leishmania a topic of high relevance. The results gathered so far encourages further investigation and introduce new concepts on gene expression regulation in this organism The attempts to demonstrate a RNAi machinery in L. major were unsuccessful, which might be due to molecular differences that are inherent to any given organism. Therefore, our proposal is to investigate the mode of action of a particular ncRNA, named ODD3, whose expression exerts a clear effect on the expression of other genes and results in drastic phenotypic changes. The interaction among RNA molecules will be investigated in order to understand the role of their sequence and the secondary structure they form in the observed effect. The possible interaction between transcripts and proteins mediating the effect of ODD3 transcript excess will also be investigated. In another sub-project on gene expression regulation we will investigate the ribosomal protein L19, which is differentially expressed during the L. major life cycle... (AU)

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Scientific publications (9)
(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)
RUY, PATRCIA DE CASSIA; TORRIERI, RAUL; TOLEDO, JULIANO SIMOES; ALVES, VIVIANE DE SOUZA; CRUZ, ANGELA KAYSEL; RUIZ, JERONIMO CONCEICAO. Intrinsically disordered proteins (IDPs) in trypanosomatids. BMC Genomics, v. 15, . (06/50323-7)
AZEVEDO, ALINE; TOLEDO, JULIANO S.; DEFINA, TANIA; PEDROSA, ANDRE L.; CRUZ, ANGELA K.. Leishmania major phosphoglycerate kinase transcript and protein stability contributes to differences in isoform expression levels. Experimental Parasitology, v. 159, p. 222-226, . (06/50323-7, 99/12403-3)
DE TOLEDO, JULIANO S.; AMBROSIO, SERGIO R.; BORGES, CARLY H. G.; MANFRIM, VIVIANE; CERRI, DANIEL G.; CRUZ, ANGELA K.; DA COSTA, FERNANDO B.. In Vitro Leishmanicidal Activities of Sesquiterpene Lactones from Tithonia diversifolia against Leishmania braziliensis Promastigotes and Amastigotes. Molecules, v. 19, n. 5, p. 6070-6079, . (06/07308-7, 06/50323-7)
NUNES, VINICIUS S.; DAMASCENO, JEZIEL D.; FREIRE, RAIMUNDO; TOSI, LUIZ R. O.. The Hus1 homologue of Leishmania major encodes a nuclear protein that participates in DNA damage response. Molecular and Biochemical Parasitology, v. 177, n. 1, p. 65-69, . (06/50323-7)
ALVES-FERREIRA, ELIZA V. C.; TOLEDO, JULIANO S.; DE OLIVEIRA, ARTHUR H. C.; FERREIRA, TIAGO R.; RUY, PATRICIA C.; PINZAN, CAMILA F.; SANTOS, RAMON F.; BOAVENTURA, VIVIANE; ROJO, DAVID; LOPEZ-GONZALVEZ, ANGELEZ; et al. Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient. PLoS Neglected Tropical Diseases, v. 9, n. 9, . (09/01641-4, 06/50323-7, 11/02040-4, 10/20597-3)
DE ALMEIDA-BIZZO, JANAYNA HAMMES; ALVES, LYSANGELA RONALTE; CASTRO, FELIPE F.; FERREIRA GARCIA, JULIANA BORIO; GOLDENBERG, SAMUEL; CRUZ, ANGELA KAYSEL. Characterization of the pattern of ribosomal protein L19 production during the lifecycle of Leishmania spp.. Experimental Parasitology, v. 147, p. 60-66, . (06/50323-7)
DE TOLEDO, JULIANO SIMOES; JUNQUEIRA DOS SANTOS, ANDRE F.; DE MOURA, TATIANA RODRIGUES; ANTONIAZI, SIMONE APARECIDA; BRODSKYN, CLAUDIA; DE OLIVEIRA, CAMILA INDIANI; BARRAL, ALDINA; CRUZ, ANGELA KAYSEL. Leishmania (Viannia) braziliensis transfectants overexpressing the miniexon gene lose virulence in vivo. Parasitology International, v. 58, n. 1, p. 45-50, . (06/50323-7, 99/12403-3)
VASCONCELOS, E. J. R.; TERRAO, M. C.; RUIZ, J. C.; VENCIO, R. Z. N.; CRUZ, A. K.. In silico identification of conserved intercoding sequences in Leishmania genomes: Unraveling putative cis-regulatory elements. Molecular and Biochemical Parasitology, v. 183, n. 2, p. 140-150, . (08/04969-8, 06/50323-7)
FERREIRA, TIAGO R.; ALVES-FERREIRA, ELIZA V. C.; DEFINA, TANIA P. A.; WALRAD, PEGINE; PAPADOPOULOU, BARBARA; CRUZ, ANGELA K.. Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection. Molecular Microbiology, v. 94, n. 5, p. 1085-1102, . (10/01129-9, 06/50323-7, 11/02040-4, 10/20597-3)

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