Abstract

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 additional single nucleotide polymrphisms (SNPs) from genes on chromosome 1, 2, 4, 5, 6, 13 and 14 of Plasmodium falciparum. To study chromosomal haplotypes, population structures, and recombination rate variation, we have also genotyped 183 SNPs on chromosome 3 from 99 worldwide isolates. This data set is being analyzed for publication. We found that recombination rate vary 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 evaluating 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000892-04
Application #
6987001
Study Section
(LID)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

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

Showing the most recent 10 out of 39 publications