Mitochondrial Genetics: Mitochondrial genome engineering to unravel the genetic links between mitochondrial gene regulation and human disease for future mechanism-based therapies

在真核生物中，几乎所有的遗传信息都是在细胞核中的DNA中编码的，但线粒体中有一个小的DNA分子，线粒体是为细胞提供食物能量供细胞使用的细胞结构。线粒体DNA包含对细胞生理功能至关重要的基因，而导致线粒体DNA功能障碍的基因缺陷可能会导致人类疾病。我们仍然不知道线粒体基因到底是如何工作的。研究基因的作用或发现其生物学功能的方法之一是改变或干扰DNA，然后寻找对培养细胞或整个生物体的影响。这些基因修饰方法通常是研究细胞核中编码的疾病基因的有效方法，但它们在应用于哺乳动物线粒体DNA方面具有挑战性。此外，许多调节线粒体功能的基因仍然未知。因此，我们的研究目标是寻找新的调控线粒体的基因，确定这些线粒体基因是如何运作的，并提供允许哺乳动物线粒体DNA进行基因修饰的技术。这可能是了解线粒体疾病和推进治疗方法探索的一种宝贵方式。

In eukaryotic organisms almost all genetic information is encoded in DNA present in the nucleus of the cell, but a small DNA molecule inhabits mitochondria, cellular structures that provide energy from food for the cells to use. Mitochondrial DNA contains genes that are vital for the physiological functioning of the cell, and genetic defects causing dysfunction of mitochondrial DNA can lead to human diseases. We still do not know how mitochondrial genes work exactly. One of the ways to investigate the role of a gene, or to discover its biological function, it to change or disrupt DNA, and then to look for the effect on cultured cells, or on the whole organism. These methods of genetic modification are often powerful ways of studying disease genes encoded in the nucleus, but they are challenging to be applied to mammalian mitochondrial DNA. Also, many genes regulating mitochondrial function are still unknown. Therefore, our research goals are to identify new genes regulating mitochondria, define how these mitochondrial genes operate and to provide the technology to allow mammalian mitochondrial DNA to be modified genetically. It could be an invaluable way of understanding mitochondrial diseases and for advancing the quest for therapies.