| Grant number: | 14/24170-5 |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| Effective date (Start): | June 01, 2015 |
| Effective date (End): | May 31, 2019 |
| Field of knowledge: | Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms |
| Acordo de Cooperação: | Coordination of Improvement of Higher Education Personnel (CAPES) |
| Principal Investigator: | Maria Carolina Quartim Barbosa Elias Sabbaga |
| Grantee: | Marcelo Santos da Silva |
| Host Institution: | Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil |
| Associated research grant: | 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling, AP.CEPID |
| Associated scholarship(s): | 17/18719-2 - Structural analysis of the origin recognition complex (ORC) in Trypanosoma brucei using cryo-electron microscopy and single-particle analysis, BE.EP.PD |
Abstract Trypanosoma cruzi is a flagellated protozoa belonging to Trypanosomatidae family, and etiologic agent of Chagas's disease, a neglected disease that affects millions of people worldwide. To survive, these parasites require replicate their DNA adequately, which involves a coordinated action of many proteins. DNA replication starts with the licensing of a pre-replication machinery (pre-RC) in specific regions of DNA called origins of replication. The dynamics and the proteins involved in pre-RC assembly are not well established in trypanosomatids. Thus, we intend to identify and characterize potential TcOrc1/Cdc6 interactors, which would be responsible for the recognition and activation of replication origins in T. cruzi. To do this, we will perform capture assays (immunoprecipitation and co-immunoprecipitation), identify the molecules in SDS-PAGE and mass spectrometer, and confirm their role in replication by knockout. In parallel, we will perform pull down assays using TcOrc1/Cdc6 recombinant, marked with different tags (6xHis and MBP) to see if this protein oligomerizes. If so, this oligomerization will be confirmed by in vitro and in vivo assays. In addition, we also intend to evaluate how the DNA metabolic processes (transcription and repair) influence the replication rate in this parasite. In this direction, we will inhibit transcription (using ±-manitin), induce DNA damage (using UV radiation and H2O2) and check, through the SMARD (Single Molecule Analisys of Replicated DNA) technique, possible alterations in DNA replication rate. It is worth mentioning that this knowledge may assist future antiparasitary strategies, since DNA replication is related directly to chromosome maintenance and cell viability. (AU) | |
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