Unique functions of the mitochondrial tRNA import machinety in T. gondii

弓形虫线粒体 tRNA 输入机制的独特功能

基本信息

批准号：
8425182
负责人：
Lilach Sheiner
金额：
$ 9万
依托单位：
UNIVERSITY OF GEORGIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-05-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8425182
关键词：
Address Affinity Chromatography Amino Acyl Transfer RNA Animal Model Apicomplexa Biochemical Biogenesis Bioinformatics Biological Biological Process Biology Biomedical Research Bypass Candidate Disease Gene Cell Line Core Facility Data Defect Development Drug Targeting Electron Transport Engineering Environment Essential Genes Faculty Falciparum Malaria Fostering Foundations Gene Pool Generations Genes Goals HIV Hand Homologous Gene Human Immunocompromised Host Individual Infection Institution Intervention Kinetoplastida Malaria Measures Membrane Potentials Mentors Messenger RNA Methods Mitochondria Mitochondrial Proteins Modeling Molecular Names Organ Transplantation Organelles Organism Parasites Pathway interactions Patients Pattern Pharmaceutical Preparations Phase Phylogenetic Analysis Plasmodium Plastids Post-Translational Protein Processing Postdoctoral Fellow Poverty Preparation Process Protein Import Proteins Protocols documentation Publishing Reagent Relative (related person)Research Research Design Research Personnel Role Scientist Source System Toxoplasma Toxoplasma gondii Toxoplasmosis Transfer RNA Transgenic Organisms Translations Transplant Recipients Trypanosoma brucei brucei Vaccines Work base biodefense career congenital infection design experience genetic manipulation insight interest malarone member method development mortality mutant neglect novel positional cloning post-doctoral training public health relevance skills tool

项目摘要

DESCRIPTION (provided by applicant): The applicant, Lilach Sheiner, is highly accomplished in Toxoplasma gondii genetic manipulation, and has recently developed a pipeline to identify and characterize genes encoding unique components of parasite endosymbiotic organelles. During the mentored phase, the applicant will utilize this system and focus on the identification and disruption of parasite-specific components of mitochondrial tRNA import (MITI) that are likely suitable as new drug targets. Furthermore the candidate will develop tools to characterize the biological function of MITI components, and will master the relevant biochemical skills, with the help of the mentors. As an independent investigator at an institution of basic biomedical research, she will apply these molecular and biochemical tools to study MITI and other parasite-specific aspects of mitochondrial biogenesis, as a promising source for drug targets. The CTEGD fosters a highly collaborative research environment with 19 faculty members interested in various aspects of parasite biology and with excellent core facilities. The mentor, Boris Striepen, is an expert on endosymbiont biology in T. gondii and is one of the leading scientists in the field of molecular research in these parasites. The co-mentor, Stephen Hajduk, is an expert biochemist with wide ranging experience in parasite mitochondria biogenesis, and who has specific interest in MITI in parasites. The T. gondii mitochondrion is essential and shows several unique features. Recent data suggests that MITI in these parasites is likely to be dependent on a divergent machinery. The goal of this proposal is to identify the components responsible for this divergence, utilizing a novel bioinformatics search strategy, and to address their function by reverse genetics, using a new streamlined system to generate conditional mutants. While some tools to characterize tRNA import and mitochondrial function in T. gondii are at hand, others await development and adaptation. Isolation of pure mitochondria has not been established, which limits the extent of biochemical research available. This challenge will be addressed in the proposed project. These studies will open new perspectives on the biogenesis of the T. gondii mitochondrion and hence contribute to the design of new countermeasures, also of relevance to other apicomplexan parasites such as the causative agent of malaria, Plasmodium falciparum.

描述（由申请人提供）：申请人Lilach Sheiner在弓形虫基因操纵中取得了高度的成就，最近开发了一条管道，以识别和表征编码寄生虫内生物植物细胞器的独特成分的基因。在指导阶段，申请人将利用该系统，并将重点放在线粒体TRNA进口（MITI）的寄生虫特异性组件（MITI）上可能适合作为新药物靶标的识别和破坏。此外，候选人将开发工具来表征MITI组件的生物学功能，并在导师的帮助下掌握相关的生化技能。作为基本生物医学研究机构的独立研究者，她将应用这些分子和生化工具来研究线粒体生物发生的MITI和其他寄生虫特异性方面，作为药物靶标的有希望的来源。 CTEGD促进了高度协作的研究环境，其中19位对寄生虫生物学各个方面和出色核心设施感兴趣的教职员工。这位导师鲍里斯·斯特里彭（Boris Striepen）是T. gondii的内共生生物学专家，并且是这些寄生虫分子研究领域的主要科学家之一。同事斯蒂芬·哈杜克（Stephen Hajduk）是一位专家生物化学家，在寄生虫线粒体生物发生方面拥有广泛的经验，并且对寄生虫的MITI特别感兴趣。 T. gondii线粒体是必不可少的，并且显示了几个独特的特征。最近的数据表明，这些寄生虫中的MITI可能取决于不同的机械。该提案的目的是确定负责这种差异的组件，利用新型的生物信息学搜索策略，并使用新的简化系统来生成条件突变体，并通过反向遗传学来解决其功能。虽然某些用于表征T. gondii中tRNA导入和线粒体功能的工具却在手头，而另一些则在等待开发和适应。尚未建立纯线粒体的分离，这限制了可用的生化研究的程度。该挑战将在拟议的项目中解决。这些研究将开辟有关t. gondii线粒体生物发生的新观点，因此有助于设计新的对策，也与其他Apicomplexan寄生虫有关，例如疟疾的病因，疟原虫恶性。