In order to maintain health of the organism, cells have developed various methods to facilitate the removal of unwanted or damaged components that could adversely affect cell function. One such method is the intracellular degradation pathway mitophagy which destroys mitochondria that have become damaged due to stress or disease. This project aims to understand some of the cellular and molecular mechanisms that drive this process.
The energy producer of the cell, the mitochondria, is prone to substantial damage throughout life. Efficient degradation of these damaged entities is therefore essential to maintain the healthy state of the cell and to limit production of harmful products that would otherwise lead to cell death. A specialised pathway within the cell known as autophagy plays a crucial role as the cell's rubbish bin, which degrades unwanted or damaged components within the cell.
This studentship project will investigate the mechanisms of a selective form of autophagy, mitophagy, which effectively degrades mitochondria following their damage. This project will utilise gene-editing approaches coupled to in situ proximity dependent labelling techniques to understand the cellular and molecular mechanisms of protein recruitment to damaged mitochondria and their regulation of mitophagy. The outcomes of this project will have implications in neurodegenerative diseases such as Parkinson's where mutations in essential mitophagy proteins are known to be associated with familial, inherited forms of the disease.
Principle Investigator (PI):
Dr David Tumbarello
Secondary Supervisor:
Dr J Arjuna Ratnayaka
Funding:
Wessex Medical Research Trust
Funding Duration:
October 2017-September 2021