The organisms studied are the human malaria parasite, Plasmodium falciparum, and the related Apicomplexan parasite Toxoplasma gondii, with emphasis on whole genome approaches to their genetics and molecular and biological phenotypes. Computer analyses, including application of several new algorithms, have been carried out, in close collaboration with experimental laboratories, in response to questions arising about the structures, functions, interactions and genetics of the genes and gene products, including those involved in the cell cycle, the intracellular parasite developmental cycle, drug and vaccine development, drug resistance and evasion of the immune response, and genetic diversity and evolution in parasite populations. These analyses include genetic mapping, quantitative and population genetics, high-throughput gene expression data, and comparative approaches with other extensively sequenced parasites, pathogens and eukaryotic genomes. Several parasites show extreme bias in the residue compositions of both genes and proteins. These compositional properties, together with questions about the roles of low-complexity, repeat, nonglobular and conformationally mobile parts of proteins, are relevant to aspects of the pathogenicity of these organisms and their interactions with the mammalian hosts. Aspects of malaria parasite biology under study include the evolution and mechanisms of complex drug resistance, antigen structure and variation, evasion of the immune response, novel aspects of genome organization and gene expression. Aspects of Toxoplasma under investigation include virulence, drug responses, the cell cycle, and multiple partially correlated phenotypes involved in the various intricate stages of host-parasite interactions.

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Intramural Research (Z01)
Project #
1Z01LM000026-15
Application #
7735066
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2008
Total Cost
$120,701
Indirect Cost
Name
National Library of Medicine
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Taylor, S; Barragan, A; Su, C et al. (2006) A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii. Science 314:1776-80
Khan, Asis; Taylor, Sonya; Su, Chunlei et al. (2005) Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii. Nucleic Acids Res 33:2980-92
Su, Xin-zhuan; Wootton, John C (2004) Genetic mapping in the human malaria parasite Plasmodium falciparum. Mol Microbiol 53:1573-82
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Fidock, D A; Nomura, T; Talley, A K et al. (2000) Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol Cell 6:861-71

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