Computational Biology and Genetics Of Malaria Parasites

疟疾寄生虫的计算生物学和遗传学

• 批准号: 6988451
• 负责人: JOHN C. WOOTTON
• 金额: --
• 依托单位: NATIONAL LIBRARY OF MEDICINE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6988451
• 关键词: Plasmodium; Plasmodium falciparum; biochemical evolution; computational biology; computer assisted sequence analysis; computer system design /evaluation; conformation; drug resistance; functional /structural genomics; genetic strain; host organism interaction; microorganism immunology; microorganism metabolism; parasite infection mechanism; pharmacogenetics; protein sequence; protein structure function; proteomics; protozoal antigen; protozoal genetics

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 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 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.

研究的主要生物体是人类疟疾寄生虫，恶性疟原虫，重点是对其遗传学和分子及生物表型的全基因组方法。与实验室密切合作，针对基因和基因产物的结构、功能、相互作用和遗传学问题，包括药物和疫苗开发、抗药性和免疫反应逃避、寄生虫种群的遗传多样性和进化等问题，进行了计算机分析，包括应用若干新算法。这些分析包括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。几种疟原虫在基因和蛋白质的残基组成上显示出极端的偏差。这些组成特性，连同低复杂性，重复，nongolobular和构象移动的部分的蛋白质的作用的问题，这些生物体的致病性和它们与哺乳动物宿主的相互作用的方面有关。正在研究的疟疾寄生虫生物学方面包括复杂抗药性的演变和机制、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。