Analysis of long non-protein-coding RNAs involved in stress mechanisms in Schistosoma mansoni

• Grant number: 24/16545-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2026
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Murilo Sena Amaral
• Grantee: Agatha Fischer Carvalho
• Host Institution: Instituto Butantan. São Paulo , SP, Brazil
• Associated research grant: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes, AP.TEM

Abstract

Schistosoma mansoni is the trematode responsible for causing schistosomiasis in Brazil, a neglected tropical disease that affects more than 200 million people worldwide. The search for new therapeutic targets is necessary since praziquantel (PZQ), the only drug used for disease control, has been associated with the development of parasite resistance and is ineffective against young parasites (schistosomula). Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with little or no protein-coding potential that have been proposed as pharmacological targets in human diseases. Specifically in S. mansoni, our group has already shown that lncRNAs are modulated under different conditions, including in vivo PZQ treatment, and that lncRNAs are crucial for the homeostasis and fertility of adult worms. Rhesus macaques are considered a unique model for studying schistosomiasis, as studies from our group have shown that they are capable of self-curing from a primary infection and challenge with S. mansoni, developing a robust immune response. We have also shown that schistosomula incubated with plasma from self-cured rhesus macaques show reduced viability and altered expression of lncRNAs and genes involved in autophagy. In this project, we aim to test the hypothesis that lncRNAs altered in response to the immune stress induced by incubation with rhesus macaque plasma are essential for the homeostasis and development of S. mansoni schistosomula, representing potential new therapeutic targets. LncRNAs previously identified by RNA-Seq will initially be validated by RT-qPCR and subsequently tested in functional phenotypic in vitro silencing studies to assess their involvement in schistosomula development. The set of experiments proposed here will indicate the essentiality of lncRNAs for the homeostasis and development of S. mansoni schistosomula, potentially revealing new therapeutic targets against schistosomiasis.