In a recent WCMR Science Seminar, we heard from PhD student Alia Saeed about her research project that involves investigating the role of mito-nuclear genetic interactions in the inheritance of pathogenic mtDNA variants. Read on to find out more.

Ever since first learning about the mitochondrion ─ from its vital role in our cells, to its contribution to processes like aging, I found it fascinating. Above that, the fact that it is of a bacterial origin, inherited exclusively through the maternal line made it unique, and gave it a sentimental value to me! This long-time interest has driven me to choose to pursue my PhD at the WCMR, working with Prof Robert Taylor, Dr Sarah Pickett and Dr Gavin Hudson, I will dedicate the next three years to try and further our knowledge in the inheritance of mtDNA pathogenic variants and the involved genetic interplay.

Mitochondrial DNA (mtDNA) is a maternally-inherited, multi-copy genome that has the potential to be heteroplasmic ─ meaning that there can be a mixture of different populations of mtDNA in a single cell. Some of these mtDNA molecules may carry a pathogenic variant, which can cause disease at high enough levels.

Different mtDNA variants can be acquired throughout our lifetime but also inherited. It is, however, very difficult to predict the level of a pathogenic variant that a mother will pass on to her child. For example, a mother with a relatively low heteroplasmy level can have children with levels that vary immensely (from 5% up to 100%). The yet unexplained, and unpredictable difference in the degree of mtDNA heteroplasmy a disease carrier, or an affected mother can transmit to her offspring, is the centre of my PhD project, which aims to identify cellular pathways involved in this transmission.