Mitochondrial disease caused by ATAD3 rearrangments: Unravelling the complexity
- Research Opportunity
- Honours, Master of Biomedical Science
- Number of Honour Places Available
- Number of Master Places Available
- Royal Children’s Hospital/Murdoch Childrens Research Institute
|Doctor Ann Frazieremail@example.com||03 9936 6602||Personal web page|
|Professor David Thorburnfirstname.lastname@example.org||Personal web page|
Summary Little is known about why hominids have 3 ATAD3 genes and whether they are functionally redundant. This project will therefore utilize a range of molecular biology, cell biology and biochemical techniques to evaluate the individual ATAD3s and their contribution to cellular and mitochondrial functions.
Mitochondria are our cellular power plants that burn sugars, fats and proteins to generate energy. Mutations in genes affecting mitochondrial energy generation and function can lead to mitochondrial disease. These diseases are both genetically and clinically heterogenous, with nearly 300 genes now known to cause mitochondrial disease. We and others have identified mutations in the ATAD3 gene cluster as causing mitochondrial diseases with a wide range of clinical severity. The ATAD3 gene locus encodes 3 highly homologous proteins and arose via tandem duplication events. Only hominids have three ATAD3 genes, with other multicellular organisms carrying only a single copy. Due to the high sequence homology and complexity within the locus, many of the disease causing mutations identified so far have included complicated structural genomic rearrangements, such as deletions, duplications and gene conversions. While ATAD3 is implicated in cellular cholesterol and mitochondrial DNA homeostasis, the precise molecular function of ATAD3 within mitochondria is not well resolved. Furthermore, little is known about why hominids have 3 ATAD3 genes and whether they are functionally redundant. This project will therefore utilize a range of molecular biology, cell biology and biochemical techniques to evaluate the individual ATAD3s and their contribution to cellular and mitochondrial functions. Investigations will include measurement of ATAD3 ATPase activities, generation and characterization of knock-out cell lines using CRISPR/Cas9 gene editing and complementation with stably expressed ATAD3s, use of "Long Read" DNA Sequencing technologies and assessment of ATAD3 protein complexes.
Faculty Research Themes
School Research Themes
Honours, Master of Biomedical Science
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Research NodeRoyal Children’s Hospital/Murdoch Childrens Research Institute
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