research groups

Biology and Biochemistry of Trypanosoma Cruzi

summary

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is one of the 17 Neglected Tropical Diseases listed by the World Health Organization. It is endemic in 21 Latin American countries and the number of patients in non-endemic developed countries is also increasing due to human migrations. Currently, between 5 and 6 million people are infected, of which less than 1% receive treatment, and it is estimated that it causes 7,000 deaths annually. Trypanosoma cruzi has a complex life cycle that includes cell differentiation processes and adaptation to different environments, such as the intestine of the vector insect, the cell cytoplasm, and the blood environment of different mammals. The lines of research developed in this lab point to the study of various relevant processes in the life cycle of Trypanosoma cruzi with the aim of finding new chemotherapeutic targets against this neglected disease.
GROUP DIRECTOR
Serra, Esteban C.

Sede:

Facultad

Email:

serra@ibr-conicet.gov.ar
Project Directors
  • Cribb, Pamela
Associated researchers
  • Alonso, Victoria
PhD POST-Fellows
PhD Fellows
  • Attala, Lucia
  • Boselli, Victoria
  • De Hernandez, Azul
  • Martinez Peralta, Gonzalo
  • Rodriguez Araya, Elvio
Undergraduate Students
  • Baldasseroni, Lucila
  • Vernetti Tauil, Alma
technicians

RESEARCH LINES

Bromodomains and acetylated proteins in Trypanosoma cruzi

Protein acetylation is one of the most frequent post-transcriptional modifications in eukaryotic cells and bacteria. Although the molecular bases of its action are not fully understood, it has been established that acetylation modulates important cellular processes such as the modification of chromatin structure, transcription, cell cycle progression, regulation of energy metabolism and microtubules dynamics. In many cases, acetylation generates a site of interaction between proteins, through an acetylated lysine recognition motif called the bromodomain (BD). This domain is the only known structural motif with specificity to recognize and bind acetylated lysines and has been exclusively described in nuclear proteins. Trypanosoma cruzi has seven BD-containing proteins designated TcBDF1 through TcBDF7, two of which are non-nuclear.

The general objective of the research line is to study the existence of nuclear and extranuclear bromodomain proteins in T. cruzi that participate in the modulation of different cellular events mediated by acetylation as potential points of intervention in the biology of the parasite to develop new chemotherapy drugs. In particular, we are studying the role of these proteins and acetylation itself in DNA transcription and repair, in the dynamics of the cytoskeleton, and during the infection and differentiation process.

The High Mobility Group B protein of Trypanosoma cruzi: a multifunctional component in the parasite-host interaction in Chagas disease

High mobility group B proteins (HMGB) participate in the control of nuclear processes due to their ability to modify the structure of chromatin. Additionally, HMGB1 is released by damaged cells or actively secreted in response to a danger signal, thus acting as an “alarmin” to alert the immune system. T. cruzi HMGB (TcHMGB) is expressed throughout the parasite’s life cycle, varying in accordance with changes in chromatin structure and replication and transcription rates. Its overexpression affects the parasite’s growth and infectivity. We hypothesize that TcHMGB contributes to the establishment of “relaxed” chromatin regions increasing DNA accessibility and thus regulating DNA transcription, replication, or repair. We also observed that TcHMGB can induce the production of inflammatory mediators like its human ortholog, and it can be secreted by the different stages of the parasite. TcHMGB is thus probably playing a role in immunity against T. cruzi infection. Our aim is to study the roles of TcHMGB, both in the regulation of nuclear functions and in regard to its interaction with the immune system of the vertebrate host.

Images of our research lines

PUBLICATIONS AND PATENTS

Essential Bromodomain TcBDF2 as a Drug Target against Chagas Disease.

ACS Infectious Diseases. Pezza, A., Tavernelli, L. E., Alonso, V. L., Perdomo, V., Gabarro, R., Prinjha, R., Rodríguez Araya, E., Rioja, I., Docampo, R., Calderón, F., Martin, J., & Serra, E. (2022).

Essential Bromodomain TcBDF2 as a Drug Target against Chagas Disease.

ACS Infectious Diseases. Pezza, A., Tavernelli, L. E., Alonso, V. L., Perdomo, V., Gabarro, R., Prinjha, R., Rodríguez Araya, E., Rioja, I., Docampo, R., Calderón, F., Martin, J., & Serra, E. (2022).
DOI

Alpha-Tubulin Acetylation in Trypanosoma cruzi: A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression.

Frontiers in Cellular and Infection Microbiology, 11.Alonso, V. L., Carloni, M. E., Gonçalves, C. S., Martinez Peralta, G., Chesta, M. E., Pezza, A., Tavernelli, L. E., Motta, M. C. M., & Serra, E. (2021).

Alpha-Tubulin Acetylation in Trypanosoma cruzi: A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression.

Frontiers in Cellular and Infection Microbiology, 11.Alonso, V. L., Carloni, M. E., Gonçalves, C. S., Martinez Peralta, G., Chesta, M. E., Pezza, A., Tavernelli, L. E., Motta, M. C. M., & Serra, E. (2021).
DOI

A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression.

Journal of Biological Chemistry, 295(38), 13202–13212. Pagura, L., Tevere, E., Merli, M. L., & Cricco, J. A. (2020).

A new model for Trypanosoma cruzi heme homeostasis depends on modulation of TcHTE protein expression.

Journal of Biological Chemistry, 295(38), 13202–13212. Pagura, L., Tevere, E., Merli, M. L., & Cricco, J. A. (2020).
DOI

Overexpression of Trypanosoma cruzi High Mobility Group B protein (TcHMGB) alters the nuclear structure, impairs cytokinesis and reduces the parasite infectivity.

Scientific Reports, 9(1).Tavernelli, L. E., Motta, M. C. M., Gonçalves, C. S., da Silva, M. S., Elias, M. C., Alonso, V. L., Serra, E., & Cribb, P. (2019).

Overexpression of Trypanosoma cruzi High Mobility Group B protein (TcHMGB) alters the nuclear structure, impairs cytokinesis and reduces the parasite infectivity.

Scientific Reports, 9(1).Tavernelli, L. E., Motta, M. C. M., Gonçalves, C. S., da Silva, M. S., Elias, M. C., Alonso, V. L., Serra, E., & Cribb, P. (2019).
DOI

Discovery of a Biologically Active Bromodomain Inhibitor by Target-Directed Dynamic Combinatorial Chemistry.

ACS Medicinal Chemistry Letters, 9(10). García, P., Alonso, V. L., Serra, E., Escalante, A. M., & Furlan, R. L. E. (2018).

Discovery of a Biologically Active Bromodomain Inhibitor by Target-Directed Dynamic Combinatorial Chemistry.

ACS Medicinal Chemistry Letters, 9(10). García, P., Alonso, V. L., Serra, E., Escalante, A. M., & Furlan, R. L. E. (2018).
DOI

contacto@conicet.gov.ar

Sede CCT Rosario

Ocampo y Esmeralda, Predio CONICET-Rosario
2000 Rosario, Santa Fe, Argentina
Tel. 54-341-4237070 / 4237500 / 4237200

Sede Facultad de Ciencias Bioquímicas y Farmacéuticas

Universidad Nacional de Rosario - Suipacha 531
2000 Rosario, Santa Fe, Argentina
Tel. +54 341 4350596 / 4350661 / 4351235

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