Computational Biology and Genetics Of Malaria and Toxopl

研究的生物体是人类疟疾寄生虫、恶性疟原虫和相关的顶复门寄生虫弓形虫，重点是对其遗传学以及分子和生物表型的全基因组方法。与实验实验室密切合作，进行了计算机分析，包括应用几种新算法，以回答有关基因和基因产物的结构、功能、相互作用和遗传学的问题，包括涉及药物和疫苗开发、耐药性和逃避免疫反应以及寄生虫种群遗传多样性和进化的问题。这些分析包括遗传图谱、定量和群体遗传学，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。几种疟原虫物种在基因和蛋白质的残基组成方面表现出极大的偏差。这些组成特性，以及有关蛋白质的低复杂性、重复、非球状和构象移动部分的作用的问题，与这些生物体的致病性及其与哺乳动物宿主的相互作用的各个方面相关。正在研究的疟原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。

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.