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Cell biology and molecular genetics of hemoparasites

Abstract

Hemoparasites are parasites that multiply inside the bloodstream. Plasmodium, the causative agent of malaria in mammals, and Babesia, the causative agent of babesiosis, are hemoparasites belonging to the phylum apicomplexa that invade and multiply inside erythrocytes. These parasites are a huge problem for human and animal health. Plasmodium is the most important human parasite with an estimated annual death toll of 1 million people. Babesia in bovines is responsible for an immense financial loss in agribusiness around the world. This project has two focuses. First to study Babesia cell biology using mutants, applying the recently available technique of transfection of B. bovis and mutation by double crossing over. Second, to generate a platform for pre-clinical tests of vaccine formulations against the malaria caused by P. vivax, the most prevalent in Brazil, by the generation of mutant hybrid murine Plasmodium (P. berghei) expressing antigens of P. vivax. The results of this project will help us to better understand the cellular and molecular mechanisms involved in the blood cycle of Babesia, leading to the development of new control alternatives and possibly allowing the proposition of this parasite as a model to study the cellular and molecular mechanisms that are conserved in the phylum apicomplexa. Moreover, the generation of mutant murine plasmodia for pre-clinical vaccine trials against P. vivax will fill a gap in this field, accelerating the process of testing vaccine formulations and ultimately the development of a vaccine against the most prevalent malaria in Brazil. It is important to note that in the state of Sao Paulo (or in Brazil) there are no laboratories working with reverse genetics in Plasmodium, a gap to be filled in Brazilian malariology. Moreover, very few laboratories in the world, none in Brazil, work with cellular biology and reverse genetics of Babesia bovis. These aspects emphasize the innovative character of this project. (AU)

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Scientific publications (9)
(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)
LIMA, MARILIA N. N.; NEVES, BRUNO J.; CASSIANO, GUSTAVO C.; GOMES, MARCELO N.; TOMAZ, KAIRA C. P.; FERREIRA, LETICIA T.; TAVELLA, TATYANA A.; CALIT, JULIANA; BARGIERI, DANIEL Y.; MURATOV, EUGENE N.; et al. Chalcones as a basis for computer-aided drug design: innovative approaches to tackle. Future Medicinal Chemistry, v. 11, n. 20, p. 2635-2646, . (17/02031-1, 13/13119-6, 17/02353-9, 17/18611-7, 12/16525-2, 18/24878-9)
CALIT, JULIANA; DOBRESCU, IRINA; GAITAN, XIOMARA A.; BORGES, MIRIAM H.; RAMOS, MARISE S.; EASTMAN, RICHARD T.; BARGIERI, DANIEL Y.. Screening the Pathogen Box for Molecules Active against Plasmodium Sexual Stages Using a New Nanoluciferase-Based Transgenic Line of P-berghei Identifies Transmission-Blocking Compounds. Antimicrobial Agents and Chemotherapy, v. 62, n. 11, . (13/13119-6, 16/16649-4, 14/23083-1)
LIMA, MARILIA N. N.; MELO-FILHO, CLEBER C.; CASSIANO, GUSTAVO C.; NEVES, BRUNO J.; ALVES, VINICIUS M.; BRAGA, RODOLPHO C.; CRAVO, PEDRO V. L.; MURATOV, EUGENE N.; CALIT, JULIANA; BARGIERI, DANIEL Y.; et al. QSAR-Driven Design and Discovery of Novel Compounds With Antiplasmodial and Transmission Blocking Activities. FRONTIERS IN PHARMACOLOGY, v. 9, . (13/13119-6, 16/16649-4, 15/20774-6, 12/16525-2, 17/02353-9)
BARGIERI, DANIEL Y.; THIBERGE, SABINE; TAY, CHWEN L.; CAREY, ALISON F.; RANTZ, ALICE; HISCHEN, FLORIAN; LORTHIOIS, AUDREY; STRASCHIL, URSULA; SINGH, PALLAVI; SINGH, SHAILJA; et al. Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes. CELL HOST & MICROBE, v. 20, n. 5, p. 618-630, . (13/13119-6)
LIMA, MARILIA N. N.; BORBA, JOYCE V. B.; CASSIANO, GUSTAVO C.; MOTTIN, MELINA; MENDONCA, SABRINA S.; SILVA, ARTHUR C.; TOMAZ, KAIRA C. P.; CALIT, JULIANA; BARGIERI, DANIEL Y.; COSTA, FABIO T. M.; et al. Artificial Intelligence Applied to the Rapid Identification of New Antimalarial Candidates with Dual-Stage Activity. CHEMMEDCHEM, v. 16, n. 7, p. 1093-1103, . (15/20774-6, 13/13119-6, 17/18611-7, 18/24878-9, 18/07007-4, 19/21854-4)
KRISHNAN, KARTHIK; ZINIEL, PETER; LI, HAO; HUANG, XIULI; HUPALO, DANIEL; GOMBAKOMBA, NITA; GUERRERO, SANDRA MENDOZA; DOTRANG, THOAI; LU, XIAO; CARIDHA, DIANA; et al. Torin 2 Derivative, NCATS-SM3710, Has Potent Multistage Antimalarial Activity through Inhibition of P. falciparum Phosphatidylinositol 4-Kinase (Pf PI4KIII ss). ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, v. 3, n. 5, p. 948-964, . (13/13119-6)
DOBRESCU, IRINA; DE CAMARGO, TARSILA MENDES; GIMENEZ, ALBA MARINA; MURILLO, OSCAR; AMORIM, KELLY NAZARE DA SILVA; MARINHO, CLAUDIO ROMERO FARIAS; SOARES, IRENE SILVA; BOSCARDIN, SILVIA BEATRIZ; BARGIERI, DANIEL YOUSSEF. Protective Immunity in Mice Immunized With P. vivax MSP1(19)-Based Formulations and Challenged With P. berghei Expressing PvMSP1(19). FRONTIERS IN IMMUNOLOGY, v. 11, . (13/13119-6, 14/50631-0, 12/13032-5, 14/23083-1, 18/17364-9, 18/20468-0)
LIMA, MARILIA N. N.; CASSIANO, GUSTAVO C.; TOMAZ, KAIRA C. P.; SILVA, ARTHUR C.; SOUSA, BRUNA K. P.; FERREIRA, LETICIA T.; TAVELLA, TATYANA A.; CALIT, JULIANA; BARGIERI, DANIEL Y.; NEVES, BRUNO J.; et al. Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits. FRONTIERS IN CHEMISTRY, v. 7, . (18/05926-2, 13/13119-6, 18/07007-4, 17/02353-9, 17/18611-7, 12/16525-2, 18/24878-9, 15/20774-6)
FERREIRA, LETICIA TIBURCIO; RODRIGUES, JULIANA; CASSIANO, GUSTAVO CAPATTI; TAVELLA, TATYANA ALMEIDA; PERALIS TOMAZ, KAIRA CRISTINA; BAIA-DA-SILVA, DJANE CLARYS; SOUZA, MACEJANE FERREIRA; DO NASCIMENTO LIMA, MARILIA NUNES; MOTTIN, MELINA; ALMEIDA, LUDIMILA DIAS; et al. Computational Chemogenomics Drug Repositioning Strategy Enables the Discovery of Epirubicin as a New Repurposed Hit for Plasmodium falciparum and P. vivax. Antimicrobial Agents and Chemotherapy, v. 64, n. 9, . (13/13119-6, 15/03553-6, 15/20774-6, 18/24878-9, 17/01986-8, 17/02031-1)

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