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.

所研究的主要生物是人类疟疾寄生虫，恶性疟原虫，重点是全基因组的遗传学方法以及分子和生物学表型。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。