The overarching theme of my lab is the biology, physiology and pathophysiology of mitochondria, especially in relation to cellular calcium signalling, although we have wandered into other aspects of cell biology especially in relation to neurodegenerative disease.
Mitochondrial integrity and energy homeostasis are key to cell health; multiple aspects of mitochondrial function have a major impact on cell health, function and fate – energetic competence, trafficking and dynamics, turnover, processing of intermediary metabolites and cell death pathways.
This is all so fundamental, that it is not surprising that mitochondrial dysfunction is implicated in the pathophysiology of a wide range of major human diseases. It is therefore critical to understand the mechanisms by which the health of the mitochondrial population is maintained, how mitochondria contribute to cell and organ physiology and pathophysiology and to understand pathways that
regulate mitochondrial function and bioenergetic homeostasis, how these change in specific diseases, and then to ask whether these represent useful potential therapeutic targets. Interests of the lab have extended through a wide range of biological problems in which mitochondria are involved – in ischaemia reperfusion injury in the heart, in the role of mitochondrial function in fertility in the mammalian oocyte, in mitochondrial function and septic shock syndrome in liver, kidney and muscle, in mitochondrial biogenesis following exercise and training in muscle, and in mitochondrial dysfunction in beta cells in diabetes. This has a positive influence on all our work, as resolving problems in one system almost always illuminates problems with others.
Our main approach involves the application of fluorescence imaging and microscopy, respirometry and protein chemistry using cells – primary neurons, astrocytes or microglia, iPS derived cells, freshly isolated cardiomyocytes, primary myotubes or appropriate cell lines – grown in culture. We have our own culture facility. We are currently actively engaged in generating neurons and muscle cells from skin fibroblasts from patients after reprogramming as induced pluripotent stem cells as models of human genetic diseases. We have also worked using explant cultures, acute slices or intact organ systems ex vivo.
We have access to state of the art confocal, multiphoton and wide field imaging systems, a biochemistry and molecular biology lab, our own tissue culture facility and we are also equipped with state of the art respirometry, FACS and high throughput imaging facilities.
