Computational Biology and Genetics Of Malaria and Toxoplasma Parasites

研究的生物是人类疟疾寄生虫，恶性疟原虫和相关的顶复合体寄生虫弓形虫，重点是对其遗传学和分子生物学表型的全基因组方法。与美国国立卫生研究院资助的校外实验实验室密切合作，进行了计算机分析，包括应用若干新算法，以回答有关基因和基因产物的结构、功能、相互作用和遗传学方面的问题，包括与细胞周期、细胞内寄生虫发育周期、药物和疫苗开发、耐药性和逃避免疫反应有关的问题。以及寄生虫种群的遗传多样性和进化。这些分析包括遗传作图、定量和群体遗传学、高通量基因表达数据，以及与其他广泛测序的寄生虫、病原体和真核生物基因组的比较方法。一些寄生虫在基因和蛋白质的残基组成上都表现出极端的偏倚。这些组成特性，连同关于蛋白质的低复杂性、重复、非小叶和构象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进化和种群多样性、抗原结构和变异、逃避免疫反应、基因组组织和基因表达的新方面。弓形虫正在研究的方面包括毒力、药物反应、细胞周期和宿主-寄生虫相互作用的各种复杂阶段。

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 NIH-funded extramural 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 evolution and population diversity, 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 the various intricate stages of host-parasite interactions.