Long non-coding RNAs expressed in Schistosoma mansoni parasites resistant to praziquantel

• Grant number: 24/18400-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 13, 2025
• End date: February 24, 2025
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Sergio Verjovski Almeida
• Grantee: Gabriella Rodrigues Nascimento
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Our group studies large-scale changes in gene expression in the parasite Schistosoma mansoni, focusing on the search for long non-coding RNAs (lncRNAs) that are essential for maintaining its homeostasis, and lncRNAs that are involved in maturation, development and in the pairing of parasites. We used molecular and cellular biology approaches to characterize the molecular mechanisms of gene expression regulation of some selected lncRNAs. The objective is to identify lncRNAs that are possible therapeutic targets against schistosomiasis. The only currently recommended treatment is the drug praziquantel (PZQ). Although safe, PZQ is unable to eliminate immature worms, does not prevent reinfection and has been used in mass administration programs, which contributes to the emergence of parasite resistance. Recent studies in the literature revealed that the primary target of PZQ in S. mansoni is an ion channel from the transient potential receptor family, Sm.TRPMPZQ. The gene encoding the channel is in a genomic locus with genetic variants (QTL) detected in subpopulations of S. mansoni with increased resistance to PZQ. However, these genetic variants associated with PZQ resistance were found only in genomic regions outside of protein-coding genes, suggesting the contribution of other regulatory genomic elements to the PZQ resistance phenotype. Given this, one of the ongoing projects in our group seeks to identify long non-coding RNAs (lncRNAs) from S. mansoni expressed in the vicinity of the genomic locus of the Sm.TRPMPZQ gene, and which are possibly involved in the development of S. mansoni parasite resistance to PZQ. The project is being carried out by scientific initiation student Pedro J. Poli, supervised by Dr. Murilo S. Amaral, a researcher in our group. The PAPL-EVC program fellow will work under my supervision and will work together with student Pedro Poli in manually curating the bioinformatics analyzes of public data, which were carried out in our group, to identify differentially expressed lncRNAs associated with the PZQ-resistant phenotype. She will discuss the experimental design and will perform one of the RT-qPCR assays to validate the expression of these lncRNAs. She will discuss the design of in vitro silencing assays that will be used to functionally assess the involvement of candidate lncRNAs in the development of PZQ resistance. This will be the first study to identify lncRNAs possibly involved in drug resistance in a parasite, and the PAPL-EVC program fellow will discuss how the study can contribute to a better understanding of PZQ resistance in S. mansoni.The PAPL-EVC scholarship holder will also participate in the weekly scientific seminar, where she will have the opportunity to contribute to the discussion of the results of several other research projects underway in our group. (AU)