Targeting mitochondrial dysfunction

Metabolism is defined as the chemical transformations within our bodies to sustain life.

The pathways of these transformations are deeply interconnected and heavily regulated to ensure a healthy and dynamic system. The mitochondrial network forms a central hub for these pathways and is the main site for aerobic energy conversion.

Disturbances of mitochondrial function have been observed in several common pathologies such as neurodegeneration, heart failure, inflammation, diabetes, and the naturally occurring ageing process.

Additionally, there are thousands of conditions associated with rare diseases, many of them displaying or caused by mitochondrial dysfunction.

However, there are no efficient treatment strategies available to alleviate mitochondrial derangements, mainly due to our lack of understanding the interconnectivity of intermediary metabolism. New and personalised therapeutic approaches are therefore necessary. This project will identify and study cellular pathways that rescue mitochondrial dysfunction in vivo.

Preliminary results from my laboratory identified four genetic modifiers in a partial genome-wide genetic screen that rescued the lethal phenotype of flies with mitochondrial dysfunction.

Combining a comprehensive genetic, proteomic, and metabolomic analysis in fruit flies, mouse models, and patient samples, will allow me to develop a detailed understanding of human metabolism under disease conditions and identify novel treatment strategies for mitochondrial dysfunction.

With my extensive research on mitochondrial biology, as well as being a clinically active physician working with patients suffering from inborn errors of metabolism, I am in a unique position to successfully lead this project.