Malaria Parasite Sexual Development and Drug Resistance

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The Malaria Genomic Unit uses the malaria parasite genome databases and develops new resources to study the mechanism of drug resistance, gene regulation during parasite sexual development, and parasite population diversity and evolution. Building on progress made last year, we have now collected single nucleotide polymorphisms (SNPs) from genes (~5000) on all of the 14 chromosomes of Plasmodium falciparum. We are currently working to develop a platform that will allow us to genotype large number of SNPs. We also have an IRB protocol approved for collecting parasites from field sites in Cambodia. To study chromosomal haplotypes, population structures, and recombination rate variation, we genotyped 183 SNPs on chromosome 3 from 99 worldwide isolates. We found that recombination rate varied greatly among parasite populations and across chromosome 3. We have also finished sequencing the mitochondrial genome from 176 P. vivax isolates and 5 other primate malaria species. Our data support the hypothesis of host switches and origin of P. vivax from Asian monkeys. Another major effort of our laboratory is to study gene expression and regulation associated with the parasite sexual differentiation. We have identified a gene that may play a key role in gametocyte development using microarray and genetic mapping. Phenotypic changes are being evaluated after genetic knockout of the target gene. We are currently studying the function of the gene. Monoclonal antibodies against gametocyte were produced, and the target proteins recognized by the antibodies are being identified. The potential of the antibodies in blocking transmission are also being tested.