Computational Biology and Genetics Of Malaria Parasites

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The principal organism studied is the human malaria parasite, Plasmodium falciparum, with emphasis on genome-wide approaches to its 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 proteins of interest, and genetic diversity and evolution in parasite populations. These analyses include 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. Applications include vaccine design, and understanding the evasion of host immune responses, immunomodulation, and the evolution of drug resistance.