Exploring novel molecular targets in mitochondrial protein synthesis to develop treatments in mitochondrial disease

Mitochondrial diseases are usually disabling, progressive or fatal, affecting the brain, liver, skeletal muscle, heart and other organs. Our understanding of the mitochondrial protein synthesis apparatus in health and disease is still limited. Currently there are no effective cures for patients with mitochondrial disease and treatment is at best symptomatic. 

I will identify novel molecular targets in mitochondrial diseases and explore why mutations in different genes only affect certain tissues. I will study mitochondrial protein synthesis in different neuronal cell types (motor neurons, oligodendroglia cells and astrocytes) in vitro, converted from skin fibroblasts of patients with different pathogenic mutations. I will use zebrafish to explore the effect of mitochondrial translation defects in vivo. These models will improve our understanding of the molecular mechanisms of different defects of mitochondrial protein synthesis in the affected tissues and organs, and will enable the development of novel approaches for therapy. 

The long-term goal is to up-regulate or boost compensatory factors in patients with mitochondrial disease for therapy. Potentially beneficial treatments identified in this research can be further investigated in high throughput screening projects, in pre-clinical animal models and clinical trials, and if successful can be used in clinical practice.