This proposal seeks to apply concepts from evolutionary biology to the study of both human and non-human malaria parasites, with the broad goal of gaining analyzing their phylogenetic relationships and of characterizing the amount, origin and manner of maintenance of genetic diversity in various genes encoding human candidate immunogens. Four primary aims are to be pursued, including: (1) to establish phylogenetic relationships relating the various mammalian malaria parasites to each other and to those of other Haemosporina, emphasizing the origins and evolutionary history of P. falciparum and P. vivax; (2) using this phylogenetic tree as a base, to identify factors affecting the evolution of major candidate vaccine immunogens; 3) to compare the extent, origin and maintenance of genetic diversity among candidate immunogens from geographically diverse samples of P. falciparum and of P. vivax; and 4) to correlate intra-host parasite genetic diversity and clinical manifestations of disease in P. falciparum-infected children in western Kenya. Overall, the proposed body of work seeks to establish the origins of the malaria parasites, to provide a basis for developing a multivalent malaria vaccine and to define the distribution of genetic diversity among malaria parasites across a broad geographic area.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM060740-04
Application #
6628908
Study Section
Special Emphasis Panel (ZRG1-GEN (01))
Program Officer
Eckstrand, Irene A
Project Start
2000-02-01
Project End
2004-12-31
Budget Start
2003-02-01
Budget End
2004-12-31
Support Year
4
Fiscal Year
2003
Total Cost
$128,605
Indirect Cost
Name
Emory University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
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Hamel, Mary J; Poe, Amanda; Bloland, Peter et al. (2008) Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates: clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L mutation. Trans R Soc Trop Med Hyg 102:338-45
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Escalante, Ananias A; Cornejo, Omar E; Freeland, Denise E et al. (2005) A monkey's tale: the origin of Plasmodium vivax as a human malaria parasite. Proc Natl Acad Sci U S A 102:1980-5
Escalante, Ananias A; Cornejo, Omar E; Rojas, Ascanio et al. (2004) Assessing the effect of natural selection in malaria parasites. Trends Parasitol 20:388-95

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