Fellowship: Identifying genes that prevent mitochondrial DNA deletions: a targete

描述(申请人提供)：在人类中，两种老年性疾病，如心脏功能障碍，都与线粒体基因组(MtDNA)大的缺失突变的形成有关。尽管大量mtDNA缺失在人类衰老和疾病中起着重要作用，但mtDNA缺失形成的确切分子机制仍不清楚。我建议使用线虫模型，秀丽线虫，作为一个系统，从基因上筛选与形成或积累大的mtDNA缺失突变相关的基因。负责防止线粒体DNA缺失形成或积累的基因(S)的发现将从根本上为剖析与线粒体DNA缺失形成相关的遗传途径开辟新的科学途径。本研究确定的基因可以被认为是人类疾病诊断和治疗的新的基因靶点。 与公共健康相关：线粒体是在细胞中产生能量的“动力源”。线粒体的损伤与人类的衰老和疾病有关。这项研究的目的是利用特征良好的模式动物秀丽线虫来鉴定参与人类疾病线粒体DNA损伤形成的基因(S)。

DESCRIPTION (provided by applicant): In humans, both aging diseases such as cardiac dysfunction are associated with the formation of large deletion mutations in the mitochondrial genome (mtDNA). Despite the prominent role of large mtDNA deletions in human aging and disease, the exact molecular mechanism of mtDNA deletion formation remains unknown. I propose to use the model nematode, Caenorhabditis elegans, as a system to genetically screen for genes that are associated with the formation or accumulation of large mtDNA deletion mutations. The identification of the gene(s) responsible for preventing the formation or accumulation of mtDNA deletions would open up fundamentally new scientific avenues for dissecting the genetic pathways associated with mtDNA deletion formation. Genes identified by this study can be considered as new gene targets for human disease for both diagnosis and treatment. PUBLIC HEALTH RELEVANCE: Mitochondria are the "powerhouses" that create energy in cells. Damage to the mitochondria is associated with both aging and disease in humans. This goal of this research is to use the well-characterized model animal Caenorhabdidits elegans to identify the gene(s) involved in the formation of mitochondrial DNA damage in human disease.