tRNA-mod Tryps: unveiling the dynamics of the tRNAome of Trypanosoma cruzi

• Grant number: 24/16633-7
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: November 01, 2025
• End date: October 31, 2030
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Janaina de Freitas Nascimento
• Grantee: Janaina de Freitas Nascimento
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ariel Mariano Silber ; Danielle Maria Nascimento Moura ; David Mark Carrington ; Julia Pinheiro Chagas da Cunha ; Michael Barrett ; Satoshi Kimura

Abstract

Trypanosoma cruzi, the causal agent of Chagas disease, has a complex digenetic life cycle. Despite the increasing number of people affected by Chagas disease, many aspects of the biology of T. cruzi are not well understood and this lack of knowledge hinders the discovery of novel treatments. Transfer RNAs (tRNAs) are key molecules involved in protein synthesis and are the most heavily modified type of RNA. Post-transcriptional modifications (PTMs) modulate tRNA structural stability and codon-anticodon pairing. The substrates for tRNA PTMs are metabolites coming from different pathways, such as glycolysis, amino acids and lipids metabolism. Despite the biological relevance of tRNAs, very little is known about these molecules in terms of the modifications they undergo and their biosynthetic pathways in T. cruzi. Moreover, how the pool of tRNAs PTMs is regulated in response to changes in the external environment in insect and vertebrate hosts is also unknown. Hence, this project aims to investigate the dynamics of tRNA expression and its impact on the biology of T. cruzi and has the specific goals: (1) to characterize the enzymes involved in tRNA PTMs in the region of the anticodon that are present in T. cruzi; (2) to evaluate the impact of altering tRNAs PTMs pathways on the gene expression and on the life cycle of T. cruzi; (3) to analyze the changes in tRNAs PTMs patterns in varying environmental conditions; (4) to investigate the connections between biochemical pathways responsible for the tRNA PTMs and other metabolic pathways in T. cruzi. For this purpose, this project will be developed in the context of a multidisciplinary international collaborative network, the 'tRNA-mod Tryps Network'. The elucidation of the dynamics of the tRNAome of T. cruzi will allow a better understanding of the mechanisms underlying the regulation of gene expression and its connection with metabolism in this organism. (AU)