Malaria Parasite Sexual Development, Drug Resistance, and Evolution

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We have finished collecting single nucleotide polymorphisms (SNPs) from 3539 genes on all of the 14 chromosomes of Plasmodium falciparum, leading to a publication in Nature Genetics early this year. In addition to developing genome-wide SNP map, our study also identified many candidate molecules that could be under host immune selection (antigens). Based on the SNPs identified, we have developed a microarray platform (Molecular Inversion Probe or PArAllele) that allows us to genotype large numbers of SNPs in a single hybridization. Parasites are being collected from patients at our clinical field site in Cambodia. Many of the parasites have been adapted and grown in in vitro culture. DNA samples from the parasites are being prepared for hybridization. We also have been evaluating a high-density microarray with 2.5 million probes for genotyping and other studies. Our data suggested that this high-density array could be a good alternative for SNP typing. The parasite responses to different antimalarial drugs are being tested to identify mutations potentially contributing to drug resistances. Another project we are working on is ABC transporters and their roles in drug resistance in P. falaciprum. We have genetically knockout one of the ABC transporters associated with chloroquine and quinine resistances in our pervious study and are evaluating the effects of gene knockout on parasite drug responses. We have finished the data analyses of our ESTcDNA collection. Our data showed considerable gene prediction inaccuracy in the P. falciparum. In collaboration with scientists in Mexico, we have also been studying Plasmodium vivax populations and their host specificity in Southern Mexico. Our data showed that P. vivax population there could be divided into three populations that were transmitted by two different mosquito species with different efficiency. This study can potentially provide information for better understanding of the molecular mechanisms of parasite and host interaction (or host specificity). We are still interested in various aspects of parasite sexual development, particularly the biological functions of Pfmdv1 and other genes that may involve in the process of gametocyte development.