Comparative investigation of Plasmodium spp. biology derived from bone marrow and peripheral blood

• Grant number: 22/12894-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2023
• End date: June 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Fabio Trindade Maranhão Costa
• Grantee: Jéssica Rafaela dos Santos Alves
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/18611-7 - Development of new tools for search and validation of molecular targets for therapy against Plasmodium vivax, AP.TEM

Abstract

Malaria remains a major public health problem worldwide. The causative agents of malaria, Plasmodium parasites, replicate asexually in red blood cells (RBCs) and data previously published support that there is an enrichment of parasites in the hematopoietic niches of the bone marrow (BM) and spleen due to the tropism of these parasites by immature reticulocytes that are present in this environment. Previous published data showed that this enrichment in BM is important for the development of gametocytes, and parasite asexual forms, highlighting that peripheral parasitemia represents only a fraction of the total biomass of the parasite, while the majority accumulates and develops in BM and spleen. However, the mechanisms involved in the cellular tropism of this parasite are still not fully understood, and this fact represents a major bottleneck to understand parasite biology and disease pathogenesis, with implications for malaria treatment and diagnosis. Here, we hypothesized that there are phenotypic and functional differences between parasite populations developing erythrocytes in the hematopoietic niches versus those in the peripheral blood (PB). To test this hypothesis samples of BM and SP aspirates from volunteers from the Center for Hematology and Hemotherapy at UNICAMP recruited during the evaluation of remission for myelopathies and without any active hematological disease and normal complete blood count will be included. Reticulocyte populations from these tissues will be isolated and characterized by blood smear and flow cytometry. Subsequently, the cells will be used in functional assays, such as re-invasion assays, drug sensitivity, deformability (micropipette aspiration), cytoadhesion in endothelial cells and rosettes, as well as transcriptional analyses, such as bulk RNA-seq and single-cell RNAseq. The results generated in this project will give support for further assays aiming at better understanding malaria infection in the hematopoietic niches. Ultimately, these data will contribute to the improvement of current strategies for malaria diagnosis, treatment, and control transmission. Finally, it is important to highlight that the project is being carried out in partnership with researchers from the Fundação de Medicina Tropical in Manaus and the University of Glasgow, and that it is funded by FAPESP and the Medical Research Council of the United Kingdom. Furthermore, the collected data were approved by the appropriate ethics committees, allowing the standardization of tests for the development of the proposal.