A5089670066- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Research on Leishmaniasis Studies
- DNA Repair Mechanisms
- Plant Virus Research Studies
- Telomeres, Telomerase, and Senescence
- Chromosomal and Genetic Variations
- Parasitic Infections and Diagnostics
- Parasitic Diseases Research and Treatment
- Signaling Pathways in Disease
- RNA and protein synthesis mechanisms
- HIV/AIDS drug development and treatment
Instituto Butantan
2011-2022
Cycle (Germany)
2021
London School of Hygiene & Tropical Medicine
2018
Albert Einstein College of Medicine
2012
Universidade Federal de São Paulo
2011
Background Infection with Trypanosoma cruzi causes Chagas disease, a major public health problem throughout Latin America. There is no vaccine and the only drugs have severe side effects. Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology disease pathogenesis. Studies compromised complexity long-term nature infection, fact that parasites barely detectable during chronic stage. In addition, functional dissection T. has been restricted...
Telomeric and adjacent subtelomeric heterochromatin pose significant challenges to the DNA replication machinery. Little is known about how progresses through these regions in human cells. Using single molecule analysis of replicated (SMARD), we delineate programs—i.e., origin distribution, termination site location, fork rate direction—of specific telomeres/subtelomeres individual chromosomes two embryonic stem (ES) cell lines primary somatic types. We observe that can initiate within...
Histone variants play a crucial role in chromatin structure organization and gene expression. Trypanosomatids have an unusual H2B variant (H2B.V) that is known to dimerize with the H2A.Z generating unstable nucleosomes. Previously, we found H2B.V protein enriched tissue-derived trypomastigote (TCT) life forms, nonreplicative stage of Trypanosoma cruzi , suggesting this may contribute differences global transcription rates observed among parasite forms. Here, performed first genome-wide...
Trypanosoma cruzi is a protozoan parasite that the etiological agent of Chagas disease, which endemic to Latin America with reported cases in non-endemic regions such as Europe, Asia, and Oceania due migration. During its lifecycle, T. alternates between replicative non-replicative infective lifeforms. Metacyclogenesis most studied transition epimastigotes differentiate into metacyclic trypomastigotes inside gut triatomine vector. This early-branching organism presents divergent...
Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis Trypanosoma brucei, the etiological agent sleeping sickness, localized its replication boundaries multigenic transcription units. To better understand genomic in this organism, we examined by single molecule replicated DNA. We determined average speed forks procyclic and bloodstream form cells found that T. brucei rate is similar...
Chromatin associated proteins are key regulators of many important processes in the cell. Trypanosoma cruzi, a protozoa flagellate that causes Chagas disease, alternates between replicative and nonreplicative forms accompanied by shift on global transcription levels changes its chromatin architecture. Here, we investigated T. cruzi proteome using three different protocols compared it (epimastigote) (trypomastigote) high-resolution mass spectrometry. More than 2000 were identified quantified...
In eukaryotes, many nuclear processes are spatially compartmentalized. Previously, we have shown that in Trypanosoma cruzi, an early-divergent eukaryote, DNA replication occurs at the periphery where chromosomes remain constrained during S phase of cell cycle. We followed Orc1/Cdc6, a pre-replication machinery component, and proliferating antigen (PCNA), component machinery, cycle this protozoon. found that, G1 stage, Orc1/Cdc6 PCNA dispersed throughout space. During G1/S transition,...
Approximately ten million people suffer from Chagas disease worldwide, caused by Trypanosoma cruzi , with the burden predominately focused in Latin America. Sleeping sickness is another serious health problem, brucei especially sub-Saharan countries. Unfortunately, drugs currently available to treat these diseases have toxic effects and are not effective against all phases or parasite strains. Therefore, there a clear need for development of novel drug targets diseases. We propose...
Abstract DNA polymerase theta (Polθ), a member of the family A, exhibits C-terminal domain, central and an N-terminal helicase domain. Polθ plays important roles in repair via its regulating genome integrity. In addition, mammals, modulates origin firing timing MCM recruitment to chromatin. contrast, as model eukaryote, Trypanosoma cruzi two individual putative orthologs different genomic loci; one ortholog is homologous other called Polθ-polymerase Polθ-helicase, respectively. A pull-down...
The pathogenic protist Trypanosoma cruzi uses kissing bugs as invertebrate hosts that vectorize the infection among mammals. This parasite oxidizes proline to glutamate through two enzymatic steps and one nonenzymatic step. In insect vectors, T. differentiates from a noninfective replicating form nonproliferative infective forms. Proline sustains this differentiation, but date, link between metabolism differentiation has not been established. cruzi, of proline-glutamate oxidation pathway are...
Replication protein A (RPA), a heterotrimeric complex, is the major single-stranded DNA binding in eukaryotes. Recently, we characterized RPA from Trypanosoma cruzi, showing that it involved replication and damage response this organism. Better efficiency differentiation epimastigote to metacyclic trypomastigote forms was observed TcRPA-2 subunit heterozygous knockout cells, suggesting process. Here, show cellular localization changes during T. cruzi life cycle, with being detected only...
Pep5 (WELVVLGKL) is a fragment of cyclin D2 that exhibits 2-fold increase in the S phase HeLa cell cycle. When covalently bound to cell-penetrating peptide (Pep5-cpp), nonapeptide induces death several tumor cells, including breast cancer and melanoma cells.
Abstract Here, we investigated the features of replication in Trypanosoma cruzi epimastigotes based on fork speed progression, which is influenced by distinct such as DNA polymerase rate, susceptibility to damage and repair, secondary structures, transcription chromatin state. Although T. exhibits a mean (2.05 ± 0.10 kb/min) very similar other trypanosomatids, found that majority molecules replicated more slowly, with frequency distribution approximately 1 kb/min. This analysis provides...
Abstract Histone variants play a crucial role in chromatin structure organization and gene expression. Trypanosomatids have an unusual H2B variant (H2B.V) that is known to dimerize with the H2A.Z generating unstable nucleosomes. Previously, we found H2B.V protein enriched nonreplicative life forms of Trypanosoma cruzi, suggesting this may contribute differences global transcription rates observed among parasite forms. Here, performed first genome-wide profiling histone localization T. cruzi...
Trypanosoma cruzi is the etiological agent of Chagas disease, which affects millions people in Latin America. No transcriptional control gene expression has been demonstrated this organism, and 50% its genome consists repetitive elements members multigenic families. In study, we applied a novel bioinformatics approach to predict new sequence T. cruzi. A measuring 241 nt was identified found be interspersed along from strains different DTUs. This repeat mostly on intergenic regions, upstream...