Malaria causes up to 2.7 million human deaths per year. Here we plan to study the molecular basis of the host-specificity of malaria parasites in a natural population of birds. Our previous data has shown that certain strains of Plasmodium spp. are entirely host specific;they infect one species of passerine bird, but not another in the same family. Others infect many species of birds. We propose to determine how one family of proteins, the erythrocyte binding-like (EBL) proteins, varies in naturally occurring populations of birds. Work by others has shown that differences in the region II domain of EBA-175 can account for host-specificity between P. falciparum and P. reichenowi, parasites that infect humans and chimpanzees respectively. We intend to test how these genes vary in a natural population where host-specificity is apparent. In this study, bird populations provide an excellent model system for the study of malaria since they are not subject to human cultural and socio-economic patterns. Using complementary techniques of genomics, established PCR-based detection methods, and molecular phylogenetics, we have identified a candidate EBL gene from P. gallinaceum, a parasite of chickens. With this information, we shall isolate orthologous genes from natural populations of birds, with the intent to discern how host specificity accounts for the distribution of parasitic diseases. We will address these three specific objectives: 1. Characterize the erythrocyte binding-like (EBL) family of genes in Plasmodium gallinaceum of chickens. 2. Isolate orthologous genes to the EBL family in Plasmodium spp. found in African rainforest birds. 3. Determine the variation in EBL binding domains in natural populations of parasites infecting rainforest birds, and correlate genetic diversity with host-specificity. The proposal also outlines the development of the PI through the mentorship of Dr. Peter Zimmerman of Case Western Reserve University. This study is the first step in a line of inquiry that will form the basis of the PI's long-range research program and thus is an essential component of his career development plan. PUBLIC HEALTH RELEVANCE: Here we propose to study genes that confer the host specificity of malaria in a natural population of birds. The results will aid in the better understanding of host-switching in malaria and the prediction of future host switching events. Once we ascertain basic genetic factors that contribute to host-specificity, we shall be able to predict the occurrence of host switching and thus better understand malaria as an emerging disease.