Prof Michael Duchen
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 the contributions 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
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 using targeted 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.
For recent reviews, see:
- Duchen MR, Szabadkai G. Roles of mitochondria in human disease. Essays Biochem. 2010;47:115-37.
- Duchen MR. Mitochondria in health and disease: perspectives on a new mitochondrial biology. Mol Aspects Med. 2004 Aug;25(4):365-451.
We have collaborations with many groups within UCL, in affiliated institutions and beyond, both as informal collaborations or with joint grants. We hold regular meetings to discuss issues related to the common interests of each group, which can be stimulating for the group as a whole, and in which PhD students are involved
The labs have recently undergone a major refurbishment to create a group of labs designated as a Centre for Mitochondrial Physiology, including a modern biochemistry lab., extensive imaging suites and a modern tissue culture facility. The lab space is shared with Dr Gyorgy Szabadkai and his group.
I am a founding PI of the MRC Centre for Neuromuscular Research and so have extensive contacts with people involved in neuromuscular disease http://www.cnmd.ac.uk/; I am a founding PI of the UK Parkinson’s Disease consortium funded through a WT and MRC strategic award; and I am coordinator of the UCL Consortium for Mitochondrial research (UCL CfMR) http://www.ucl.ac.uk/mitochondria/ which brings together an enormous range of expertise in mitochondrial research . Each of these brings access to intellectual and technical expertise, to funding and to engagement in interesting discussion groups and journal clubs.
Work in the lab has been supported for many years by grants from the Wellcome Trust and the Medical Research Council, whom we thank. Current funding includes grants from the MRC, The Wellcome Trust, the Muscular Dystrophy Campaign, the Muscular Dystrophy Association, RNID, The British Heart Foundation, The MS Society, Kidney Research UK.
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