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Molecular sensor could reveal zinc's role in disease

4 September 2009

Zinc, a conglomerate of silver-white metal
A new molecular sensor has provided scientists with the first accurate way to measure the concentration of zinc and its location in cells.

The knowledge gained from the method, developed by researchers from Imperial College London and the Eindhoven University of Technology in the Netherlands, could offer further insight into a variety of diseases such as type 2 diabetes and Alzheimer's disease.

Zinc is involved in many processes in the body - it is required by 5 per cent of the body's proteins and is thought to play a role in many diseases. For example, it helps package insulin in pancreas cells and the gene that controls this process is often defective in people with type 2 diabetes.

Previous methods of estimating zinc concentration used crude chemical techniques that gave only a rough guide to the amount present and no indication of where it was in the cell.

The new technique uses two fluorescent proteins from jellyfish to measure the distance between zinc ions in individual cells, showing how much zinc is present.

When the proteins attach to zinc ions, they are pushed apart and the transfer of light between them becomes weaker. Using a fluorescence microscope, the researchers can detect the wavelengths of light emitted by the proteins, with coloured patches showing where in the cell the zinc is.

"We can now measure very accurately the concentration of zinc in cells and we can also look at where it is inside the cell, using our molecular measuring device," said Professor Guy Rutter from Imperial College London, one of the authors of the study.

"This sort of information will help us to see what is going on inside different tissues, for example in the brain in Alzheimer's disease where we suspect zinc may be involved. We hope this new sensor will help researchers learn more about zinc-related diseases and potentially identify new ways of treating them."

The researchers used their new sensor to look for zinc in pancreatic cells and found a high concentration of zinc ions inside certain parts of the cells where insulin is found. They hope their new sensor will help scientists find out exactly how zinc is involved in diabetes.

They now aim to develop the sensor to look at zinc in a mouse model, so that they can observe the movement of the element in different tissues.

The research in the UK was part-funded by the Wellcome Trust, alongside the Medical Research Council (UK), the European Union and Imperial College London.

Image: Zinc, a conglomerate of silver-white metal. Credit: Efraim Lev and Zohar Amar, Wellcome Images

References

Vinkenborg JL et al. Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis. Nat Methods 2009 [Epub ahead of print].

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