The broad long term objective of this project is to analyze and understand structurally and functionally the molecular make-up of Plasmodium vivax merozoites. This knowledge will identify and characterize proteins that may serve as important vivax malaria vaccine candidates or targets of anti-malaria drug interventions. Plasmodium vivax is a highly predominant malaria species, causing 80 million cases or more of malaria each year and major socioeconomic public health ramifications worldwide. Nevertheless, P. vivax is under investigated in part because it cannot be cultured reliably long term in vitro. Specialized expertise and non human primate resources are therefore required for in depth laboratory investigations on this human parasite species. Experimental models using P. vivax parasites and the related simian malaria species P. knowlesi and P. cynomolgi in non-human primates are fundamental to this research program. Plasmodium merozoites are very complex and there are many gaps in knowledge regarding the full scope of molecules involved in their adhesion to and entry into red blood cells.
The specific aims of this research are to 1) Identify novel P. vivax genes encoding merozoite proteins with surface, organellar and apical locations, 2) Investigate structural and functional characteristics of P. vivax merozoite surface and apically localized proteins and protein complexes, and 3) Develop a P. vivax model for integrated transfection and reverse genetics investigations. This research capitalizes extensively on the recent availability of Plasmodium genome databases, utilizing bioinformatics, micro-arrays, proteomics, genetic manipulation strategies, high resolution imaging capabilities, functional adhesion and invasion assays, immunochemical methods and cell biological technologies. This research will reveal new P. vivax merozoite proteins, gain a fuller understanding of the structure and coordinated expression of specific merozoite proteins and develop new knowledge on protein complexes, post translational modifications and function. As priorities, this project will also provide reagents for the broader malaria research community and develop a P. vivax blood-stage transcriptome and merozoite proteome, which will be valuable for vivax research specifically, as well as comparative genomics research aimed to distinguish features that are distinctive to the biology of P. vivax or conserved among Plasmodium parasites. Project Narrative Plasmodium vivax is a major species of malaria, which causes an estimated 80 million or greater infections annually in about 60 countries. This project aims to discover and characterize the structure and function of merozoite proteins that facilitate the successful entry of this parasite species into red blood cells, and which can serve as future malaria vaccine or drug targets.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI024710-23
Application #
8274864
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
MO, Annie X Y
Project Start
1987-03-01
Project End
2014-05-13
Budget Start
2012-06-01
Budget End
2014-05-13
Support Year
23
Fiscal Year
2012
Total Cost
$548,764
Indirect Cost
$236,966
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Moreno, Alberto; Cabrera-Mora, Monica; Garcia, Anapatricia et al. (2013) Plasmodium coatneyi in rhesus macaques replicates the multisystemic dysfunction of severe malaria in humans. Infect Immun 81:1889-904
Galinski, Mary R; Meyer, Esmeralda V S; Barnwell, John W (2013) Plasmodium vivax: modern strategies to study a persistent parasite's life cycle. Adv Parasitol 81:1-26
Jiang, Jianlin; Barnwell, John W; Meyer, Esmeralda V S et al. (2013) Plasmodium vivax merozoite surface protein-3 (PvMSP3): expression of an 11 member multigene family in blood-stage parasites. PLoS One 8:e63888
Akinyi, Sheila; Hanssen, Eric; Meyer, Esmeralda V S et al. (2012) A 95 kDa protein of Plasmodium vivax and P. cynomolgi visualized by three-dimensional tomography in the caveola-vesicle complexes (Schuffner's dots) of infected erythrocytes is a member of the PHIST family. Mol Microbiol 84:816-31
Meyer, Esmeralda V S; Semenya, Amma A; Okenu, Daniel M N et al. (2009) The reticulocyte binding-like proteins of P. knowlesi locate to the micronemes of merozoites and define two new members of this invasion ligand family. Mol Biochem Parasitol 165:111-21
Pfahler, Judith M; Galinski, Mary R; Barnwell, John W et al. (2006) Transient transfection of Plasmodium vivax blood stage parasites. Mol Biochem Parasitol 149:99-101
Rayner, Julian C; Tran, Tuan M; Corredor, Vladimir et al. (2005) Dramatic difference in diversity between Plasmodium falciparum and Plasmodium vivax reticulocyte binding-like genes. Am J Trop Med Hyg 72:666-74
Rayner, Julian C; Huber, Curtis S; Galinski, Mary R et al. (2004) Rapid evolution of an erythrocyte invasion gene family: the Plasmodium reichenowi Reticulocyte Binding Like (RBL) genes. Mol Biochem Parasitol 133:287-96
Black, Casilda G; Barnwell, John W; Huber, Curtis S et al. (2002) The Plasmodium vivax homologues of merozoite surface proteins 4 and 5 from Plasmodium falciparum are expressed at different locations in the merozoite. Mol Biochem Parasitol 120:215-24

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