Biology of the Apicomplexan Plastid

顶复体质体的生物学

• 批准号: 7740148
• 负责人: BORIS STRIEPEN
• 金额: $ 27.76万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7740148
• 关键词: Affect; Algae; Antibodies; Antiparasitic Agents; Apicomplexa; Bioinformatics; Biological; Biological Assay; Biology; Cell Cycle; Cell division; Cells; Cellular biology; Centrosome; Chloroplasts; Chromosome Segregation; Chronic; Chronology; Comparative Genomic Analysis; Complement; Cryptosporidiosis; Cryptosporidium; DNA-Directed DNA Polymerase; Data; Development; Disease; Drug Delivery Systems; Elements; Event; Fluorescence; Gene Proteins; Genes; Genetic; Genetic Screening; Genome; Genomics; Hand; Histones; Homologous Gene; Human; Laser Microscopy; Lead; Livestock; Maintenance; Malaria; Microscopic; Mitotic spindle; Modeling; Molecular; Multi-Drug Resistance; Organelles; Organism; Parasites; Pathogenesis; Pathway interactions; Pharmacological Treatment; Phenotype; Phylogenetic Analysis; Phylogeny; Plants; Plasmodium; Plastids; Positioning Attribute; Process; Proteins; Research Personnel; Resources; Role; Staging; Testing; Time; Toxoplasma; Toxoplasma gondii; Toxoplasmosis; Tubulin; antimicrobial drug; base; biodefense; comparative genomics; daughter cell; drug development; effective therapy; fascinate; gene cloning; genetic analysis; genome sequencing; in vivo; interest; knock-down; mutant; overexpression; pathogen; physical model; programs; protein function; research study; segregation

The phylumApicomplexa contains a large group of protozoan parasites responsible for numerousimportant human and livestock diseases. Several of these organisms (Toxoplasma, Cryptosporidium & Cyclospord) are also listed as type B pathogens of potential biodefense concern. Significant challenges remain in the antimicrobial drug treatment for these diseases. The discovery of a remnant chloroplast, the apicoplast, now presents several parasite specific pathways that can be exploited as specific drug targets to help overcome some of these challenges. Genomie, genetic and pharmacological data show that the apicoplast is essential for development and pathogenesis for Plasmodium and Toxoplasma validating it as a target and demonstrating the importance of the organelle for the biology of the organism. This proposal is focused on unraveling the mechanisms used by the parasite to faithfully replicate and segregate this important organelle and its genome. The chloroplast division machinery in plants and algae depends overwhelminglyon genes of cyanobacterial origin, with the bacterial tubulin homolog ftsZ being the most prominent. Our genomic analysis has not identified any clear homologs of these genes in Apicomplexa. How is the apicoplast divided in the absence of the conserved machinery? Based on our cell biological studies we hypothesize that in sharp contrast to plants the plastid in Apicomplexa is segregated using a genuinely eukaryotic mechanism ¿association with the centrosomes of the mitotic spindle. This proposal develops a number of mechanistic models to explain how the plastid is faithfully segregated into daughter cells, how fission occurs and is timed within the parasite cell- cycle, and how the replication and maintenance of the organellar genome is tied into this process. To test these hypotheses we have assembled a set of highly compatible cell biological, comparative genomic and genetic experiments. Genomic and genetic screens will permit us to further refine our hypotheses, and will help us to populate them with additional molecular players beyond the genes and proteins already in hand.

顶复合体门包含一大群原生动物寄生虫，负责许多重要的疾病