Complex I (NADH:ubiquinone oxidoreductase) is an intricate ~1 MDa multimeric membrane-bound complex that is essential for mitochondrial metabolism: its dysfunctions lead to neuromuscular and metabolic diseases and it is implicated in ischaemia-reperfusion injury.
In our research group we combine structural, biochemical and biophysical methods to study complex I, and aim to apply our molecular knowledge to understand in vivo function and dysfunction . As a central group in the MRC Mitochondrial Biology Unit, with a mission to understand mitochondrial biology in health and disease, we aim to contribute to understanding disease mechanisms, and support clinical diagnoses and development of complex I-based therapies .
This aim of this project is to combine the genetic versatility of cultured mammalian cells with an adapted toolbox of methods for assessing complex I structure and function. The project will be a collaboration with the Prudent group at the MBU, who are experts in cell biology, and will start by developing methods for evaluating and optimising complex I function and molecular integrity in cultured cells. The student working on this project will therefore learn cell culture techniques, proteomics and mass spectrometry, and microscale assay development. As the project develops there will then be opportunities to create clinically-relevant variants and determine how the complex I is affected, and/or to develop methods to isolate the enzyme for more detailed studies. The project therefore represents an exciting opportunity to develop research skills and expertise in both cell biology and biochemical approaches.
General: mammalian cell culture, mitochondria, assays, genetics, respiratory chain
More specific: complex I, redox enzyme, mitochondrial disease, rare genetic diseases