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: 7735066
• 负责人: JOHN C. WOOTTON
• 金额: $ 12.07万
• 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/7735066
• 关键词: Algorithms; Antigens; Biological; Biology; Cell Cycle; Characteristics; Chromosome Mapping; Collaborations; Complex; Computational Biology; Computers; Data; Development; Drug resistance; Evolution; 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 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 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, the cell cycle, and multiple partially correlated phenotypes involved in the various intricate stages of host-parasite interactions.

研究的生物是人类疟疾寄生虫，恶性疟原虫和相关的顶复合体寄生虫弓形虫，重点是对其遗传学和分子生物学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，包括应用几种新的算法，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、耐药性和逃避免疫反应的基因和基因产物的问题。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。一些寄生虫在基因和蛋白质的残基组成上都表现出极端的偏倚。这些组成特性，连同关于蛋白质的低复杂性、重复、非小叶和构象移动部分的作用的问题，与这些生物的致病性及其与哺乳动物宿主的相互作用有关。疟疾寄生虫生物学的研究领域包括复杂耐药性的进化和机制、抗原结构和变异、免疫应答的逃避、基因组组织和基因表达的新方面。正在研究的弓形虫的各个方面包括毒力、药物反应、细胞周期以及涉及宿主-寄生虫相互作用各个复杂阶段的多种部分相关表型。

项目成果

Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii.

• DOI: 10.1093/nar/gki604
• 发表时间: 2005
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Khan A;Taylor S;Su C;Mackey AJ;Boyle J;Cole R;Glover D;Tang K;Paulsen IT;Berriman M;Boothroyd JC;Pfefferkorn ER;Dubey JP;Ajioka JW;Roos DS;Wootton JC;Sibley LD
• 通讯作者: Sibley LD