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How DNA replication contributes for the success of infection caused by Trypanosoma cruzi

Grant number: 20/00694-6
Support type:Research Projects - Thematic Grants
Duration: December 01, 2020 - November 30, 2025
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Maria Carolina Quartim Barbosa Elias Sabbaga
Grantee:Maria Carolina Quartim Barbosa Elias Sabbaga
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Assoc. researchers:Ariel Mariano Silber ; Carlos Renato Machado ; Igor Correia de Almeida ; Jose Salvatore Leister Patane ; Julia Pinheiro Chagas da Cunha ; Luiz Ricardo Orsini Tosi ; Marcelo da Silva Reis ; Mark C. Field ; Nicolai Siegel ; Richard Mcculloch ; Simone Guedes Calderano ; Stenio Perdigão Fragoso

Abstract

DNA replication must be closely controlled to ensure reliable maintenance of the genome in daughter cells. On the other hand, it is a process that can result in mutations. The balance between a careful process and an error-prone one results in higher or lower genetic variability. The aim of this project is to investigate the replication process in Trypanosoma cruzi, from the assembly of the pre-replication complex, through the activation of origins until eventual replicative stresses, in the context of its cell and life cycle. We intend to unravel the molecular mechanisms that allow (i) blocking replication in infectious forms; and (ii) the genetic variability of this organism, which is critical to the successful of the infection of the mammalian host. Reverse genetics, enzyme tagging, and characterization of post-translational protein modification techniques will allow the investigation of pre-replication and replication complex proteins. This approach will allow us to set up a robust scenario about the molecular mechanisms that T. cruzi uses to block DNA replication in infectious forms. Using Chip-seq and Gro-seq techniques, as well as mathematical modeling, we will investigate the replication dynamics. In this sense, we intend to evaluate the contribution of genome organization in this dynamic and to identify possible regions favorable to replicative stresses that may contribute to the genetic variability in T. cruzi. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SLAVOV, SVETOSLAV N.; PATANE, JOSE S. L.; BEZERRA, RAFAEL DOS SANTOS; GIOVANETTI, MARTA; FONSECA, VAGNER; MARTINS, ANTONIO J.; VIALA, VINCENT L.; RODRIGUES, EVANDRA S.; SANTOS, ELAINE V.; BARROS, CLAUDIA R. S.; MARQUEZE, ELAINE C.; SANTOS, BIBIANA; ABURJAILE, FLAVIA; NETO, RAUL M.; MORETTI, DEBORA B.; HADDAD, RICARDO; CALADO, RODRIGO T.; KITAJIMA, JOAO P.; FREITAS, ERIKA; SCHLESINGER, DAVID; JUNIOR DE ALCANTARA, LUIZ C.; ELIAS, MARIA C.; SAMPAIO, SANDRA C.; KASHIMA, SIMONE; COVAS, DIMAS T. Genomic monitoring unveil the early detection of the SARS-CoV-2 B.1.351 (beta) variant (20H/501Y.V2) in Brazil. Journal of Medical Virology, JUL 2021. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.