Silenciamento dos genes que codificam enzimas modificadoras de histonas em estágios parasitários do Schistosoma mansoni

Abstract

Schistosomiasis is a neglected parasitic disease, caused by the species Schistosoma mansoni, which affects a total of 54 countries and 19 states in Brazil. Currently, the only drug available for treatment is Praziquantel, which is effective only against adult worms and, when used massively, can lead to the selection of resistant strains of the parasite. Epigenetics is one of the ways to study the mechanisms of pathogenesis of several diseases, including schistosomiasis, through the observation of chromatin alterations, which can be seen as alterations in posttranslational modification of the tails of histones. Histones are one of the main targets of scientific study because they are responsible for controlling gene transcription, undergoing methylation, and acetylation, among other modifications, which can activate or inhibit gene expression, being important for the progression of the life cycle of the parasite, both in its vertebrate and invertebrate host. Studies involving epigenetics will enable the development of new and modern drugs that can solve the problems faced with Praziquantel today. The main objective of this project is to carry out the silencing of the Smp_316180, Smp_053140, and Smp_034000 genes using the RNAi technique (dsRNA/epigenetic probes) in the stages of the parasite's biological cycle in which the genes are more expressed, carry out the incubation of the inhibitor specific for the Smp_034000 gene in parallel and observe the possible morphological and molecular changes in the cultures of the parasite (genetically and pharmacologically). Initially, we will prepare the dsRNA probes, using the oligonucleotides that will be designed by us, we will then carry out the cultures of each of the desired stages, and according to the methodology used in our laboratory, we will incubate the probes in the prepared cultures as well as the inhibitor of the Smp_034000 gene and we will perform the final analysis through microscopy, qRT-PCR, and Western-Blot.(AU)