Computational Biology and Genetics Of Malaria and Toxoplasma Parasites

疟疾和弓形虫寄生虫的计算生物学和遗传学

基本信息

批准号：
7594458
负责人：
JOHN C. WOOTTON
金额：
$ 17.65万
依托单位：
NATIONAL LIBRARY OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

项目摘要

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. Aspects of Toxoplasma under investigation include virulence, drug responses, and multiple partially correlated phenotypes involved in the various intricate stages of host-parasite interactions

所研究的生物是人类疟疾，恶性疟原虫和相关的Apicomplexan寄生虫弓形虫弓形虫，重点是整个基因组方法的遗传学方法以及分子和生物表型。计算机分析（包括使用几种新算法的应用）与实验实验室密切合作，以回应有关基因和基因产品的结构，功能，相互作用和遗传学的问题，包括涉及药物和疫苗的开发，耐药性，耐药性，对免疫反应，遗传多样性和遗传多样性的销售和食用销孢子的销售。这些分析包括遗传学图，定量和种群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。几种疟原虫在基因和蛋白质的残基组成中都显示出极端偏见。这些成分特性以及有关蛋白质的低复杂性，重复，非叶片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有关。研究中疟疾寄生虫生物学的各个方面包括复杂耐药性，抗原结构和变异的进化和机制，免疫反应的逃避，基因组组织的新方面和基因表达。正在研究的毒品的各个方面包括毒力，药物反应以及宿主 - 寄生虫相互作用各种复杂阶段涉及的多个部分相关的表型