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York scientists to explore link between copper and arsenic in sheep liver

Posted on 9 December 2004

Scientists at the University of York are to take part in research into a rare breed of sheep, which could yield clues for the development of a drug to treat a medical condition affecting one in 30,000 people worldwide.

The three-year study will be carried out by a collaborative team of researchers from the universities of Aberdeen, Liverpool and York, which has been awarded £413,000 by the UK's Engineering and Physical Sciences Research Council (EPSRC).

The team will use sheep whose diet comprises of pasture and seaweed. The researchers will look at the elements found in the liver of these sheep, characterised by an extremely high level of arsenic compared with a low copper level.

In the past, research has shown that the North Ronaldsay sheep have an amazing capacity to withstand huge amounts of arsenic. They ingest quantities of arsenic, which is toxic in its elemental form, at levels many times higher than are considered safe yet show no signs of being affected.

Traditionally, scientists have been interested only in the total concentration of metals in biological tissues. However, the molecular form of the metals determines the interaction with biomolecules and essential processes of life.

The first part of the study will involve the researchers trying to develop an analytical method for the determination of the molecular form of the metals found in the sheep liver. The second part will involve applying the technique with the potential to develop pharmaceuticals for people who are being treated for Wilson’s disease, a genetic disorder that causes an abnormally high copper level in the liver or brain.

One of the major aims of the project will be to establish if metals are related in any way to this disease. The initiative is being led by Professor Jörg Feldmann, Environmental Analytical Chemistry, of the University of Aberdeen in collaboration with Dr Susan Haywood, of Liverpool University and Professor Jane Thomas-Oates, of the University of York. Dr Susan Haywood has an established breeding flock of the North Ronaldsay sheep with studies already in progress on the role of copper in diseases of the liver and brain with colleagues in the School of Preclinical Veterinary Sciences. She will provide the required resource for the later work of metal (copper) speciation. Two post-docs (one from the University of Aberdeen and one from University of York) will also be working on the study.

Professor Feldmann, said: “In the last two years there has been tremendous interest in the key interaction of metals in biomolecules. This project is highly innovative, attempting to access a source of biomolecules that has not been tapped before and is the only work of its kind in the UK being carried out at this level.

“The methods that my collaborators and myself will develop in this project are generic and therefore applicable for the study of other tissues and other systems. Hence protein chemists, biochemists, toxicologists and pathologists will benefit enormously, since this approach will open up new opportunities to establish a range of metal-protein interactions.

“This study will provide essential information for the food industry in which it is important to know in which form we should take up essential metals and how toxic metals can be wrapped up. It may also provide clues about why, in cumulative amounts, metals like copper are somehow linked to metal-related diseases like Alzheimer’s, BSE, and Wilson’s disease and could pave the way for the development of drugs to treat some of these medical conditions.”