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 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, and comparative approaches with other extensively sequenced parasites, pathogens and eukaryotic genomes. Several Plasmodium species 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.

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Intramural Research (Z01)
Project #
1Z01LM000026-13
Application #
7316231
Study Section
(CBB)
Project Start
Project End
Budget Start
Budget End
Support Year
13
Fiscal Year
2006
Total Cost
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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