4 YEAR PhD IN NEUROSCIENCE
Department of Cell and Developmental Biology
Neuronal activity, mitochondrial function and cell death
Our research program focuses on the role of mitochondrial function and dysfunction to cell physiology. Projects range through contributions of mitochondrial dysfunction to changes in cell function, cell injury and death, to the contributions of mitochondria to cellular transduction processes (e.g.glucose sensing by insulin secreting pancreatic beta cells and oxygen sensing in the carotid body). We are particularly interested in the impact on mitochondria of free radical production (including NO) and changes in intracellular calcium as underlying mechanisms of cell death in excitotoxic injury during stroke and in chronic neurodegenerative disorders such as Parkinson's disease.
The roles of calcium, free radicals and mitochondrial dysfunction as precipitants of cell death in single mammalian cells.
Disordered mitochondrial function may define the borderline between changes in function that are reversible and those that progress to irreversible injury during cerebral ischaemia (stroke) and reperfusion injury in the CNS. In particular, free radicals and high intracellular calcium provoke mitochondrial dysfunction that leads to ATP depletion and cell death. We will employ fluorescence imaging techniques to study the rates of free radical production, focal calcium signalling and localised changes in mitochondrial function in single neurons and glial cells in culture under a variety of conditions, including manipulation of cellular antioxidant defence mechanisms [in collaboration with the group of Prof. John Clark, Neurochemistry, Inst. of Neurology].
Peuchen, S., Clark, J.B. & Duchen, M.R . (1995)
Mechanisms of intracellular calcium regulation in response to P2u receptor activation in adult astrocytes.
Neuroscience, in the press.
Duchen, M.R., McGuinness, O., Brown, L., & Crompton, M. (1993)
The role of the cyclosporin-A sensitive mitochondrial pore in myocardial reperfusion injury.
Cardiovascular Research, 27, 1790-1794.
Duchen, M.R. (1992)
Ca2+-dependent changes in the mitochondrial energetics of single mouse sensory neurones.
Biochemical Journal, 283, 41-50.