Evaluation of ncRNA participation on R-loops formation and its role in the regulation of gene expression and host-parasite interaction in L. braziliensis

• Grant number: 24/18411-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2025
• End date: June 30, 2028
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Adriene Yumi Ishimoto
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 23/03015-0 - Of epigenetics, genomic variability and gene expression regulation in Leishmania, AP.TEM

Abstract

Leishmaniasis is a tropical disease caused by obligate intracellular parasites of the genus Leishmania. The clinical manifestations of Leishmaniasis depend on the infecting species, genetic factors and the host's immune response, and can be divided into two main forms: Cutaneous or Mucocutaneous Leishmaniasis, and Visceral Leishmaniasis. Macrophages are the first line of defense against Leishmania, and in the context of infection, these parasites face a hostile environment for their survival and for the establishment of infection, requiring mechanisms to evade the host's immune response and subvert these resources in their favor. The subversion of macrophage defense mechanisms in favor of Leishmania is associated with rapid changes in the expression profile of genes involved in the production and secretion of virulence factors that maintain this pathogen-host interaction. ncRNAs play an important role in post-transcriptional regulation and in the processes such as differentiation, virulence and adaptation to stress. Recently, it has been observed that ncRNAs also participate in the formation of R-loops, structures with an important function in the control of gene replication, repair and transcription. Therefore, in this project we will address the biological functions of ncRNAs in L. braziliensis, focusing on the identification of ncRNAs that participate in the formation of R-loops, and their possible dual nature as cis or trans regulatory elements as independent transcripts, or in the formation of R-loops associated with DNA. Thus, the main objective of this project is to map the ncRNAs of L. braziliensis that colocalize with R-loops and that are preferentially expressed in amastigotes, seeking to understand their possible functions and whether these ncRNAs act as regulatory elements of gene expression, in order to investigate their effects against infection, characterizing targets and mechanisms behind these structures. (AU)