MITOCHONDRIAL MEDICINE AND BIOLOGY

Fig 1. Mitochondrial mRNAs are transcribed as part of long primary transcripts that generally encompass the entire mtDNA, therefore the ratios of the 11 mammalian mitochondrial mRNAs and their proteins are controlled post-transcriptionally. Little is known about how these 11 mRNAs are regulated in mammalian mitochondria. This is particularly important since tissue-, cell- and disease-specific variations in expression of mitochondrial RNAs has been observed, but cannot be explained at present. The basic components and mechanisms of transcription have recently been discovered, however the control of mRNA processing, translation and stability remains unclear.

We are interested in identifying mammalian mitochondrial RNA-binding proteins and investigating their role in RNA metabolism in cells. Discovery of proteins and the RNAs they bind may shed light on the regulation of gene expression in mammalian mitochondria. In addition, we are developing new methods for the identification of mitochondrial RNAs bound by the mitochondrial RNA-binding proteins that may regulate their expression in health and in disease.

Identification of mutations that cause mitochondrial disease

Mitochondrial diseases are progressive and debilitating multi-system disorders that occur as a result of mutations in nuclear or mitochondrial genes with no known cures to date. The clinical heterogeneity in mitochondrial disorders is complemented by genetic heterogeneity, where mutations in mitochondrial or nuclear genes cause similar phenotypes thus complicating mutation identification. We use next generation technologies to identify mutations in DNA from patients that suffer from mitochondrial diseases to identify the mutations that cause these diseases. We use patient cells to investigate how mutations in mitochondrial genes cause the molecular changes that cause mitochondrial and cellular dysfunction that leads to the disease pathology.

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).

Contact
Professor Aleksandra Filipovska – [email protected]

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 use tissues from mouse models of mitochondrial diseases to investigate how specific proteins regulate gene expression and how lack of these genes can cause lead to the disease pathology. The project will use a variety of techniques ranging from genetics, immunohistochemistry, molecular and cell biology, biochemistry and next generation sequencing. 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 (RNA sequencing), molecular biology (cloning, quantitative PCR) and biochemistry (protein purification, enzyme activity measurements).

Contact
Professor Aleksandra Filipovska – [email protected]

This project will investigate a mutation in a mitochondrial gene that is required for energy production and breakdown of fats and carbohydrates. Recently we have found that this mutation slows down the breakdown of fats and as a result leads to insulin resistance, fatty liver and obesity. We are interested to understand how a single mutation can impair energy metabolism and lead to insulin resistance. Insight into this process would enable us to develop specific drugs and treatments that can overcome the impact of insulin resistance on normal body function.
This project involves the use of a range of techniques in genetics, mouse pathology and physiology, cell biology (such as cell culture, cell death assays, fluorescence microscopy, gel electrophoresis, western blotting), molecular biology (cloning, quantitative PCR, RNA interference) and biochemistry (protein purification, enzyme activity measurements).

Contact
Professor Aleksandra Filipovska – [email protected]