Mitochondrial disease caused by ATAD3 rearrangments: Unravelling the complexity

Research Opportunity
Honours, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Paediatrics
Location
Royal Children’s Hospital/Murdoch Childrens Research Institute
Primary Supervisor Email Number Webpage
Doctor Ann Frazier ann.frazier@mcri.edu.au 03 9936 6602 Personal web page
Co-supervisor Email Number Webpage
Professor David Thorburn david.thorburn@mcri.edu.au 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.

Project Details

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

Child Health

School Research Themes

Child Health in Medicine



Research Opportunities

Honours, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Paediatrics

Research Node

Royal Children’s Hospital/Murdoch Childrens Research Institute

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