This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Deciphering the pathways of host invasion is crucial to understanding malaria, one of the world's deadliest infectious diseases. Malaria is a parasitic human disease caused by four different species of Plasmodium: P. falciparum, P. vivax, P. malariae, and P. ovale. Humans have many genetic adaptations that fight malaria, such as the sickle-cell allele. This pilot project specifically examines malarial adaptation at the band 3 (SLC4A1) and the glycophorin A (GYPA) genes, which are both implicated in human resistance to malaria, specifically aspects of the disease associated with P. falciparum malaria. This project will examine DNA sequences of non-human primates to test hypotheses of the Plasmodium specificity of the genetic adaptations at SLC4A1 and GYPA to human P. falciparum. These hypotheses will be tested by pursuing the following Specific Aim. SLC4A1 and GYPA will be compared among non-human primates, to test to adaptive genetic in species which harbor and are resistant to different species of Plasmodium. Non-human primates provide unique and compelling models for understanding the genetic basis of many human diseases, including malaria. This project will join our current understanding of human and primate malaria to bioinformatics and evolutionary analyses in order to test for the parasite specificity of human adaptations to malaria. Determining the parasite specificity of human genetic adaptations to malaria is significant because it will help to detail the different pathways each parasite utilizes to infect humans, in turn yielding targets for the disruption of the infection process. Furthermore, comparative analysis of primate-Plasmodium interactions is also critical for development of the most realistic animals models for studying human malaria. This research will also help to understand a disease that was a major health issue for many Americans prior to 1940. The pilot project will make strides in pursuing the long-term research goal of a comparative understanding of how infectious diseases have shaped the genomes of humans and other primates.
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