Investigating the effect of the Drosophila mitochondrial genome on complex phenotypes (360G-Wellcome-203767_Z_16_A)

The mitochondrion, known as the powerhouse of the cell, contains its own genome (mtDNA). The multi-copy mtDNA works with the nuclear genome to control energy production and various cellular activities. To date, mtDNA mutations are among the most common genetically inherited diseases and the mitochondrial replacement therapy has been approved in the UK to make three-parent babies. However, our knowledge of mtDNA biology and how it can affect organismal traits is rather limited. This is largely due to a lack of powerful genetic tools to study mtDNA. A recent study in Ma's group shows that Drosophila mtDNA can undergo homologous recombination12. Further, they established a system to induce recombination at specific sites and select for different recombinant genomes. This work not only provides a definitive resolution to the existence of recombination in animal mitochondria, but opens up the possibility of developing a recombination system for functional mapping and manipulating animal mtDNA. In this project, I will isolate recombinant mitochondrial genomes to map/define mtDNA variations responsible for longevity and fertility to accelerate our understanding of how mtDNA impacts health. Meanwhile, I will identify key components of the recombination machinery to better understand how mtDNA is maintained during aging and evolution.