Prof Michael Duchen
Professor of Physiology
Cell & Developmental Biology
Div of Biosciences
- Joined UCL
- 1st Oct 1984
We are interested in a wide range of issues related to mitochondrial biology and cell signaling. Much of our current work is focused on interrelationships between calcium signaling, mitochondria and free radicals in cell physiology and pathophysiology. This work embraces questions about thecontributions of mitochondrial function to intracellular calcium signaling.
We are fascinated by the intimate dialogue between mitochondrial biology and cell signaling systems. How do cell signaling pathways impact on and regulate mitochondrial physiology? How do subtle changes in mitochondrial function affect the physiology of the cell? How are mitochondria in different cell types specialized to match the specialized differentiated function of the cells they inhabit? We are especially concerned to characterise the contributions of mitochondrial dysfunction to cell injury and cell death - by necrosis or apoptosis – that takes place in situations such as ischaemia, reperfusion injury and in the neurotoxicity mediated by glutamate or beta-amyloid. Another core theme again involving a complex dialogue is the mitochondrion as both a site and a target of oxidative stress and damage in disease models. Most of our work involves live cell fluorescence microscopy and imaging, including confocal, multiphoton and fast read-out cooled CCD instruments. All approaches have been adapted to allow the simultaneous or near simultaneous measurement of multiple variables - cytosolic calcium and mitochondrial potential, cytosolic calcium and mitochondrial calcium, NADH autofluorescence and cytosolic calcium or cytosolic magnesium and so on.
We have a broad general interest in functional cellular imaging and in the development of new approaches to imaging aspects of cell function usingtargeted probes, GFP tagged proteins, FRET, FLIM and so on.
Interests of the lab extend 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 egg (with John Carroll), 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 rather unusual breadth has had a positive influence on all our work, as resolving problems in one system invariably seems to illuminate problems with others. We have been astonished at the frequency with which a small number of basic principles are recapitulated in a wide and disparate array of models.
- University College London
- PhD, Physiology | 1984
- MRCP, Medicine | 1981
- St George's Hospital Medical School
- MBBS, Medicine/Surgery | 1978
- University of Oxford
- BA, Physiology | 1975
Michael was born in South Africa, moving to the UK in 1960. He studied Physiology and Medicine in Oxford, 1971-75, then moved to St George's Hospital Medical School to complete his clinical training, graduating 1978. he worked in clinical medicine in junior hospital appointments 1978-1981 including a period working at a rural hospital in the Transkei, South Africa. He moved to the UCL Department of Physiology to embark on PhD studies 1981 -1984 with Tim Biscoe as supervisor and mentor. He has stayed at UCL Physiology (now the Department of Cell and Developmental Biology) ever since, first as a Royal Society University Research Fellow, then as Reader and Professor. His early research was electrophysiological with an interest in neurotransmitter receptor biology, but he became interested first in the influence of cell metabolism on excitability and then increasingly fascinated by mitochondrial biology, in the dialogue between cell signalling pathways and mitochondria, in the roles of mitochondria in disease and ultimately in the question of whether mitochondrial pathways represent viable therapeutic targets in a variety of disease states.