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

• 批准号: 7969203
• 负责人: JOHN C. WOOTTON
• 金额: $ 12.9万
• 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/7969203
• 关键词: Algorithms; Antigens; Biological; Biology; Cell Cycle; Characteristics; Chromosome Mapping; Collaborations; Complex; Computational Biology; Computers; Data; Development; Drug resistance; Evolution; Extramural Activities; Funding; Gene Expression; Gene Proteins; Genes; Genetic; Genetic Variation; Genome; Goals; Human; Immune response; Investigation; Laboratories; Malaria; Modeling; Molecular; Molecular Genetics; Organism; Parasites; Pathogenicity; Pharmaceutical Preparations; Phenotype; Plasmodium falciparum; Population; Population Genetics; Property; Proteins; Role; Staging; Structure; Toxoplasma; Toxoplasma gondii; Variant; Virulence; base; comparative; novel; pathogen; response; vaccine development

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.

研究的生物体是人类疟疾寄生虫，恶性疟原虫，以及相关的Apicomplexan寄生虫弓形虫，重点是全基因组方法，其遗传学和分子和生物表型。与NIH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，包括那些参与细胞周期、细胞内寄生虫发育周期、药物和疫苗开发、抗药性和逃避免疫反应，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。几种寄生虫在基因和蛋白质的残基组成方面表现出极端的偏倚。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进化和种群多样性、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。研究中的弓形虫包括毒力、药物反应、细胞周期和宿主-寄生虫相互作用的各个复杂阶段。