Computational Biology and Genetics Of Malaria and Toxoplasma Parasites

被研究的生物是人类疟疾寄生虫恶性疟原虫和与之相关的Apicomplexan寄生虫弓形虫，重点是研究它们的遗传学和分子生物学表型的全基因组方法。与实验实验室密切合作，针对基因和基因产品的结构、功能、相互作用和遗传学方面出现的问题，包括参与细胞周期、细胞内寄生虫发育周期、药物和疫苗开发、抗药性和免疫反应的逃避以及寄生虫种群的遗传多样性和进化的问题，进行了计算机分析，包括应用了几种新的算法。这些分析包括遗传图谱、数量和群体遗传学、高通量基因表达数据，以及与其他广泛测序的寄生虫、病原体和真核基因组的比较方法。几种寄生虫在基因和蛋白质的残基组成上都表现出极端的偏向。这些组成性质，以及关于蛋白质的低复杂性、重复、非小叶和构象可移动部分的作用的问题，与这些生物的致病性及其与哺乳动物宿主的相互作用有关。正在研究的疟疾寄生虫生物学方面包括复杂耐药性的进化和机制、抗原结构和变异、免疫反应的逃避、基因组组织和基因表达的新方面。正在研究的弓形虫的方面包括毒力、药物反应、细胞周期以及参与宿主-寄生虫相互作用的各个复杂阶段的多种部分相关的表型。

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.