Conditional probes of secretory protein function in malaria parasites

疟原虫分泌蛋白功能的条件探针

• 批准号: 8494563
• 负责人: Sean Taylor PRIGGE
• 金额: $ 19.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494563
• 关键词: Binding Proteins; Biological; Biology; Cells; Cytosol; Destinations; Development; Disease; Dominant-Negative Mutation; Drug Kinetics; Drug Targeting; Drug resistance; Endoplasmic Reticulum; Erythrocytes; Event; Future; Genetic; Genome; Goals; Golgi Apparatus; Human; In Vitro; Iron; Knock-out; Life Cycle Stages; Ligand Binding; Ligands; Malaria; Mammals; Mediating; Methods; Molecular; Mutation; Organelles; Organism; Parasites; Pathway interactions; Peptide Signal Sequences; Peptides; Plasmodium falciparum; Play; Process; Property; Protein Secretion; Proteins; RNA Interference; Research; Rodent; Role; Sorting - Cell Movement; Structure; Sulfur; System; Techniques; Therapeutic Intervention; Transgenic Organisms; Ubiquitination; Vacuole; Validation; Vesicle; design; extracellular; in vivo; mouse model; nutrient metabolism; protein function; secretory protein; tool; trafficking

DESCRIPTION (provided by applicant): Genetic methods to control protein levels are extremely valuable tools for probing the basic biology of any organism. Two commonly employed tools are RNA interference and conditional expression, neither of which has been successfully implemented in malaria research. We are developing a new method to control proteins in the secretory pathway of malaria parasites. Over 20% of the proteins encoded by the Plasmodium falciparum genome are thought to pass through the secretory system on their way to organellar or extracellular destinations. These proteins have key roles in parasite metabolism, nutrient acquisition, invasion, host cell remodeling, and other critical aspects of parasite biolog. The goal of this project is to design and optimize a conditional probe to control the localization f soluble secretory proteins in P. falciparum. This method will then be validated by applying it to two biological targets: one in the apicoplast organelle and one which resides in the parasitophorous vacuole. Successful development of a conditional localization tool will enhance our ability to probe the basic biology of malaria parasites and will allow us to validate potential targets for therapeutic intervention.

描述（由申请人提供）：控制蛋白质水平的遗传方法是探测任何生物体基本生物学的极有价值的工具。两种常用的工具是RNA干扰和有条件的表达，在疟疾研究中都没有成功实施。我们正在开发一种在疟疾寄生虫分泌途径中控制蛋白质的新方法。据认为，超过20％的由恶性疟原虫基因组编码的蛋白质在前往细胞器或细胞外目的地的途中通过分泌系统。这些蛋白质在寄生虫代谢，养分，入侵，宿主细胞重塑以及寄生虫生物学的其他关键方面具有关键作用。该项目的目的是设计和优化有条件的探针，以控制恶性疟原虫中的定位f溶解性分泌蛋白。然后将通过将其应用于两个生物学靶标来验证该方法：一种中的一种在寄生虫液泡中，一种位于Apicopopoppolast Organelle中。有条件定位工具的成功开发将增强我们探测疟疾寄生虫基本生物学的能力，并使我们能够验证潜力 治疗干预的目标。