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Details of Grant 

EPSRC Reference: EP/M024393/1
Title: How does respiratory complex I pumps protons? Finding the missing link using EPR spectroscopy.
Principal Investigator: Roessler, Dr MM
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Delft University of Technology
Department: Sch of Biological and Chemical Sciences
Organisation: Queen Mary University of London
Scheme: First Grant - Revised 2009
Starts: 01 August 2015 Ends: 31 January 2018 Value (£): 100,373
EPSRC Research Topic Classifications:
Analytical Science Catalysis & Applied Catalysis
Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
12 Feb 2015 EPSRC Physical Sciences Chemistry - February 2015 Announced
Summary on Grant Application Form
The rising age of the UK population presents one of the major challenges to our society and economy and it is vital that we maximise the contribution of the most experienced individuals by increasing the number of years we live in best possible health. The mitochondrial respiratory chain, which is essential for the production of ATP and a prime source of reactive oxygen species, is thought to have a major influence on the rate at which we age. Moreover, defects in the respiratory chain are responsible for mitochondrial diseases - these are rare, but their outcome is often very severe, if not fatal. Their diagnosis is fraught with difficulties and there is no cure.

Complex I is a crucial but poorly understood element in the mitochondrial respiratory chain and we propose to elucidate a particularly important aspect of the mechanism of this essential enzyme by employing a multidisciplinary approach. We will study the bovine enzyme, a close relative of human complex I, employing in particular electron paramagnetic resonance (EPR) spectroscopy, a powerful method for investigating chemical centres having unpaired electrons. In complex I such unpaired electrons are naturally present or can be generated in mechanistically highly informative locations and we will harness the information they provide through advanced pulse EPR and biochemical methods.

Our work will constitute a major step forward in obtaining a complete picture of the molecular mechanism of one of the most important, largest and most enigmatic enzymes in our bodies, with long-term implications for increasing our healthy lifespan and for the recognition and treatment of mitochondrial diseases resulting from complex I dysfunction. Our proposed research program will have immediate impact on UK science, with academic beneficiaries in a diverse range of research disciplines. We will provide top-quality interdisciplinary training for the EPSRC PDRA (and at least two Queen Mary University undergraduate research project students), to provide expertise at the interface of chemistry and biology, with a quantitative approach to fundamental biochemical problems.

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