Mitochondria are microscopic, energy producing machines that are found in all human cells. Mitochondria contain a small set of genes that must work properly to make the energy our bodies require for health. Defects in the expression of mitochondrial genes cause debilitating diseases for which there are no cures currently. We will use new genomic, molecular and cell biology technologies to identify new mutations that lead to disease and understand how the mutations cause the disease pathology at a molecular level.
Mitochondrial disease are progressive and debilitating multi-system disease that occurs as a result of mutations in nuclear or mitochondrial genes at a frequency of up to 1 in 13,000 live births with no known cure. Mutations in nuclear genes that code for mitochondrial proteins have been found to cause a range of diseases including mitochondrial diseases that have the same pathologies to those observed in patients with mutations in mtDNA. We have DNA and cells from several families that suffer from mitochondrial diseases that are not the result of mtDNA mutations but mutations in nuclear genes coding for mitochondrial proteins. This project will use patient DNA to identify mutations in nuclear genes that cause mitochondrial disease and use the patient cells to investigate how the changes at the DNA level cause mitochondrial and cellular dysfunction that leads to the disease pathology. The project will use a variety of techniques ranging from genetics, next generation technologies, molecular and cell biology. This is of great importance in understanding the mechanisms underlying mitochondrial disease and may provide new avenues for therapeutic interventions.
This project involves the use of a range of techniques in genetics, cell biology (such as cell culture, cell death assays, fluorescence microscopy, gel electrophoresis, western blotting), genomics (exome sequencing), molecular biology (cloning, quantitative PCR, RNA interference) and biochemistry (protein purification, enzyme activity measurements).
Professor Aleksandra Filipovska – [email protected]