Uptake and Processing of Foreign DNA by Mitochondria, a Model System

线粒体（一种模型系统）对外源 DNA 的吸收和加工

• 批准号: 7454963
• 负责人: MICHAEL C SCHMALE
• 金额: $ 18.8万
• 依托单位: UNIVERSITY OF MIAMI ROSENTEIL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7454963
• 关键词: Animal Model; Biological Assay; Biological Models; Cell Line; Communicable Diseases; Cultured Cells; DNA; DNA Structure; DNA biosynthesis; Data; Development; Electroporation; Encapsulated; Family; Fishes; Gene Transfer Techniques; Genetic Transcription; Genome; Goals; Infectious Agent; Life Cycle Stages; Life Style; Marines; Measurement; Methods; Mitochondria; Neurofibromatoses; Neurofibromatosis 1; Organism; Parasites; Pathogenesis; Process; Reporting; Research; Research Project Grants; Risk; Source; Structure; Study models; System; Transfection; Tumor-Derived; Vertebrates; Viroids; Virus; base; design; in vitro Model; mutant; neoplastic cell; research study; success; technique development; uptake

DESCRIPTION (provided by applicant): The mechanisms by which foreign DNAs enter mitochondria are largely unknown. The goal of the proposed studies is to develop an in vitro model for study of uptake, replication and transcription of foreign DNA by mitochondria. This cell culture based model system will take advantage of a unique virus-like agent which infects and replicates in the mitochondria of tumor cells in a tropical marine fish, the bicolor damselfish (Stegastes partitus). This transmissible agent (DVLA) is associated with the naturally occurring, infectious disease termed damselfish neurofibromatosis. DVLA does not resemble any known family of virus or viroid. The unusual sequence and secondary structure of the DNA genome of this agent are likely a direct result of the apparently unique life-style of this agent and may provide clues to optimizing uptake and processing of foreign DNA by mitochondria. The aims of the proposed study are to examine the entry of DVLA DNA into isolated mitochondria and evaluate the replication and transcription of this DNA in the mitochondria. This is a high risk research project with the potential to yield data which should be widely applicable to understanding pathogenesis in mitochondria and for development of techniques for mitochondrial transgenesis in other vertebrates.

描述（由申请人提供）：外源dna进入线粒体的机制在很大程度上是未知的。本研究的目的是建立一个体外模型来研究线粒体对外源DNA的摄取、复制和转录。这种基于细胞培养的模型系统将利用一种独特的病毒样病原体，它可以感染热带海洋鱼类双色雀鲷（Stegastes partitus）肿瘤细胞的线粒体并在其中复制。这种传播因子（DVLA）与自然发生的传染性疾病有关，称为雀鲷神经纤维瘤病。DVLA不像任何已知的病毒或类病毒家族。该病原体DNA基因组的不同寻常的序列和二级结构可能是该病原体明显独特的生活方式的直接结果，并可能为线粒体优化吸收和处理外来DNA提供线索。本研究的目的是研究DVLA DNA进入分离的线粒体，并评估该DNA在线粒体中的复制和转录。这是一个高风险的研究项目，有可能产生广泛适用于了解线粒体发病机制和开发其他脊椎动物线粒体转基因技术的数据。