Ischaemia damages heart muscle and reperfusion of blood flow is vital for restoring function. Paradoxically, reperfusion itself can cause further irreversible tissue damage. We propose to study the cellular processes that limit reperfusion injury by ischaemic preconditioning in which brief periods of ischaemia can protect against a longer lethal ischaemic episode. Recent evidence suggests that protection can be conferred by brief flickering of the mitochondrial permeability transition pore (mPTP), a process which is poorly understood. Ischaemic heart disease is a major source of death and disability and our results should inform clinical treatments and development of new therapeutic strategies.
The hypothesis is that brief mPTP openings are necessary for cardiac preconditioning and trigger signalling through reactive oxygen species production.
Specific objectives will be tested using fluorescent rhodamine dyes that detect mitochondrial membrane potential (1) to characterise the timing of mPTP opening during preconditioning (2) to determine the effect of preventing mPTP opening during preconditioning (3) to test the role of electron transport chain metabolites in mPTP opening.
Academic entry requirements: UK Bachelor Degree with at least 2:1 in a relevant subject or overseas equivalent.