Nutrition, MRC Dunn Human Nutrition Unit: University of Cambridge

The aims of the MRC Dunn Human Nutrition Unit are to study fundamental mechanisms underlying nutrition and the influence of nutrients on health and longevity. We consider the whole spectrum of complexity from molecular mechanisms to epidemiology. Our Director is Sir John Walker, Nobel Laureate in Chemistry (1997).

Key research areas

Ten closely integrated research teams are working on a range of overlapping programmes.

• One focus of their activities concerns the conversion in mitochondria of energy derived from oxidation of sugars and fats to adenosine triphosphate (ATP). Two groups are working on the structure and mechanism of the mitochondrial electron transport chain enzyme complex I from mitochondria and bacteria, using protein film voltammetry and protein chemistry and X-ray and electron crystallography (Dr Judy Hirst, Dr Leo Sazanov).
• Work on how ATP is made uses protein chemistry, genetics and crystallography to elucidate the structure and mechanism of the ATP synthase. The current emphasis is on the rotary motor and the mechanism of torque generation, and on understanding the mechanism of energy transfer into the ATP molecule (Prof JohnWalker).
• The transport of ATP, ADP, phosphate and other substrates, products and cofactors required for mitochondrial metabolism is conducted by a family of mitochondrial transporters; this family is the focus of a fourth group. The aims are to discover the functions of unidentified members of this family revealed in genome sequences and to elucidate the structure and mechanism of these important proteins (Dr Edmund Kunji).
• Work on mitochondrial diseases concentrates on mechanisms of replication of human mitochondrial DNA, respiratory consequences of pathological mitochondrial DNA mutations, and nuclear factors regulating segregation of mutant and wild-type mitochondrial DNA molecules (Dr Ian Holt).
• Their proteomics group concentrates on various aspects of the mitochondrion using mass spectrometric methods to study proteins involved in mitochondrial DNA replication, mitochondrial proteins involved in phosphorylation-dephosphorylation pathways and to characterise the subunits of complex I (Prof John Walker).
• Research into the cellular regulation of nutrient and energy turnover focuses on mitochondrial proton conductance, uncoupling proteins, reactive oxygen species and obesity, metabolic depression and ageing (Dr Martin Brand).
• Functional studies on mitochondria look at targeting of novel molecules, changes during apoptosis and necrosis in mammalian cells, radical production and oxidative damage to mitochondria (Dr Michael Murphy).
• The influence of nutrients in food and health and longevity is being pursued by our Diet, Cancer and Public Health Group. Research involves prospective diet, biomarker, hormone and genotype analyses, and investigation of mechanisms relating diet to DNA in humans in our volunteer suite (Dr Sheila Bingham).
• The bioinformatics group applies bioinformatics to study the evolution and function of proteins of the mitochondrion using comparative genomics, molecular modelling and phylogenetics. The goal is to develop models for the dynamics and control of the metabolic and bioenergetic pathways, particularly those associated with disease (Dr Alan Robinson).

Research collaborations

They have extensive research collaborations within Cambridge, including the Cambridge Institute for Medical Research (who share their building), and with other national and international institutions.

Further information:

• www.mrc-dunn.cam.ac.uk