Selective mtDNA transmission in Drosophila melanogaster

Theme: World-Class Underpinning Bioscience

There is genetic variation among mitochondrial genomes (mtDNA) within most individuals. Different variants can be selectively transmitted during development and across generations. The outcome of selection impacts the progression of mitochondrial diseases if certain variants are pathogenic. The nuclear genome is known to influence this selection process, but how is unknown. To investigate the mechanism, I use an approach based on a Drosophila melanogaster line which stably transmits two competing mitochondrial genomes over generations. This involves the production of a Drosophila cell line which also stably maintains both mitochondrial genomes and which I use for a whole-genome RNAi screen to investigate which nuclear genes affect selective mtDNA transmission in cell culture. To investigate therapeutic applications, the cells will also be used for a drug screen.

To complement the cell-based approach, effects at the organismal level are studied with a fly deficiency screen.