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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000892-07
Application #
7592263
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2007
Total Cost
$1,369,618
Indirect Cost
City
State
Country
United States
Zip Code
Raj, Dipak Kumar; Mu, Jianbing; Jiang, Hongying et al. (2009) Disruption of a Plasmodium falciparum multidrug resistance-associated protein (PfMRP) alters its fitness and transport of antimalarial drugs and glutathione. J Biol Chem 284:7687-96
Li, Jian; Zhang, Yanhui; Sullivan, Margery et al. (2007) Typing Plasmodium yoelii microsatellites using a simple and affordable fluorescent labeling method. Mol Biochem Parasitol 155:94-102
Mu, Jianbing; Awadalla, Philip; Duan, Junhui et al. (2007) Genome-wide variation and identification of vaccine targets in the Plasmodium falciparum genome. Nat Genet 39:126-30
Su, Xinzhuan; Hayton, Karen; Wellems, Thomas E (2007) Genetic linkage and association analyses for trait mapping in Plasmodium falciparum. Nat Rev Genet 8:497-506
Lu, Fangli; Jiang, Hongying; Ding, Jinhui et al. (2007) cDNA sequences reveal considerable gene prediction inaccuracy in the Plasmodium falciparum genome. BMC Genomics 8:255
Bockhorst, Joseph; Lu, Fangli; Janes, Joel H et al. (2007) Structural polymorphism and diversifying selection on the pregnancy malaria vaccine candidate VAR2CSA. Mol Biochem Parasitol 155:103-12
Cui, Long; Miao, Jun; Furuya, Tetsuya et al. (2007) PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum. Eukaryot Cell 6:1219-27
Gaur, Deepak; Furuya, Tetsuya; Mu, Jianbing et al. (2006) Upregulation of expression of the reticulocyte homology gene 4 in the Plasmodium falciparum clone Dd2 is associated with a switch in the erythrocyte invasion pathway. Mol Biochem Parasitol 145:205-15
Jiang, H; Joy, D A; Furuya, T et al. (2006) Current understanding of the molecular basis of chloroquine-resistance in Plasmodium falciparum. J Postgrad Med 52:271-6
Chiang, Peter K; Bujnicki, Janusz M; Su, Xinzhuan et al. (2006) Malaria: therapy, genes and vaccines. Curr Mol Med 6:309-26

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