Biology of the apicomplexan plastid

顶复体质体的生物学

基本信息

批准号：
8389639
负责人：
BORIS STRIEPEN
金额：
$ 31.41万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-12-01 至 2015-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389639
关键词：
Adverse effects Animal Model Apicomplexa Applied Genetics Biochemical Biological Biological Assay Biology Candidate Disease Gene Cells Cellular Structures Cellular biology Child Chloroplasts Complement Complex Cryptosporidiosis Data Defect Disease Disease Management Drug Targeting Energy-Generating Resources Epitopes Eukaryota Eukaryotic Cell Evolution Face Fetus Fruit Funding Future Genes Genetic Goals Harvest Human Immune system Individual Intervention Lead Left Life Life Cycle Stages Malaria Marriage Membrane Metabolism Mining Molecular Multi-Drug Resistance Mutagenesis Nuclear Organelles Parasites Pathway interactions Patients Pharmaceutical Preparations Plants Plastids Post-Translational Protein Processing Process Protein Import Proteins Red Algae Rest Role Source Stream Structure System Testing Toxoplasma Toxoplasma gondii Toxoplasmosis Ubiquitination base chemotherapy comparative genomics feeding functional genomics human disease insight mutant novel pathogen prenatal prevent promoter protein function public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): Apicomplexa are responsible for a number of important human diseases including malaria, toxoplasmosis, cryptosporidiosis and cyclosporidiosis. Management of these diseases rests heavily on chemotherapy but anti-parasitic drug treatment faces multiple challenges. These include poor overall potency, restriction to certain life-cycle stages, unwanted side effects, and rapidly emerging multiple drug resistance. A constant stream of new drugs and potential drug targets is required to stay abreast of the threat posed by these pathogens. One of the most promising sources of such parasite specific targets is the apicomplexan plastid or apicoplast. The apicoplast is unique to the parasite and its function is essential to parasite survival. This organelle is a holdover from a free-living photosynthetic past. The structure and biology of the apicoplast is remarkably complex as it is derived from the endosymbiotic marriage of two eukaryotes: a red alga and an auxotrophic protist. The goal of this application is to unravel the complexity of this biology in mechanistic detail and to identify future targets for intervention. Using Toxoplasma as a model organism we will conduct genetic, cell biological and biochemical approaches to characterize the function of two pathways that unfold in the outer compartments of the organelle and that we hypothesize are essential to the organelle and the parasites. We will complement this focused approach with a broader effort to define a comprehensive set of plastid proteins to continue to feed a pipeline of hypothesis-driven mechanistic experiments with strong candidate genes.

描述（由申请人提供）：Apicomplexa 导致许多重要的人类疾病，包括疟疾、弓形体病、隐孢子虫病和环孢子虫病。这些疾病的治疗很大程度上依赖于化疗，但抗寄生虫药物治疗面临着多重挑战。这些包括整体效力差、对某些生命周期阶段的限制、不良副作用以及迅速出现的多重耐药性。需要源源不断的新药和潜在药物靶点来跟上这些病原体造成的威胁。这种寄生虫特异性靶标最有希望的来源之一是顶端复体质体或顶端质体。顶质体是寄生虫所独有的，其功能对于寄生虫的生存至关重要。这种细胞器是自由生活的光合作用过去的遗留物。顶端质体的结构和生物学非常复杂，因为它源自两种真核生物的内共生婚姻：红藻和营养缺陷型原生生物。该应用的目标是从机制细节上揭示这种生物学的复杂性，并确定未来的干预目标。使用弓形虫作为模型生物，我们将进行遗传、细胞生物学和生化方法来表征细胞器外部隔室中展开的两条途径的功能，并且我们假设这两条途径对细胞器和寄生虫至关重要。我们将通过更广泛的努力来补充这种集中的方法，以定义一套全面的质体蛋白，以继续为一系列具有强大候选基因的假设驱动的机械实验提供支持。