Role of mitochondrial morphology in controlling mitochondrial DNA inheritance during Drosophila germline development

University of Cambridge

Mitochondria are small organelles primarily involved in energy production and cellular metabolism. They contain their own small circular genome, the mitochondrial DNA (mtDNA). In contrast to the chromosomal genes that occur in two copies, one inherited from the mother and one from the father, the mtDNA is found in many copies within each cell (often many 1000s), and is only inherited from the mother.

Mitochondria continuously need to adapt their shape, constantly moving, dividing and fusing, to generate a specific network answering cellular energy needs. Recent evidence has established the deregulation of mitochondrial dynamics in response to metabolic dysfunction and diseases. We have previously identified novel genes and processes that regulate mitochondrial shape and dynamics in cultured cell lines.

The broad aim of this collaborative project is to elucidate how mitochondrial shape and dynamics interacts with mtDNA maintenances during germ line development in a living organism, the fruit fly Drosophila. The project will focus on how mitochondrial morphology interacts with mtDNA elimination during sperm development, and with quality control of mtDNA mutations during stem cell and oocyte development.

To address these fundamental questions, the PhD candidate will use advanced Drosophila genetics, CRISPR/Cas9-mediated genome editing, microdissection, state-of-the-art microscopy analysis, including confocal, super-resolution and electron microscopy, as well as quantitative high-resolution live-cell imaging in order to elucidate how mitochondrial morphology controls developmental cell fate decisions and mtDNA dynamics. The candidate will be trained in quantification and statistical analysis of data, scientific reasoning, experimental design, reading papers, presentation and communication, and team-work.


General: Drosophila, mitochondria, heteroplasmy, germline

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