Think zinc: molecular sensor could reveal zinc's role in diseases

Think zinc: molecular sensor could reveal zinc's role in diseases

Scientists use jellyfish proteins to look at zinc in cells

Imperial College London News Release

Under strict embargo until
18.00 British Summer Time / 13.00 US Eastern Time
Sunday 30 August 2009

Scientists have developed a new molecular sensor that can reveal the amount of zinc in cells, which could tell us more about a number of diseases, including type 2 diabetes. The research, published today in Nature Methods, opens the door to the hidden world of zinc biology by giving scientists an accurate way of measuring the concentration of zinc and its location in cells for the first time.

Zinc is involved in many processes in the body and five percent of all the proteins made by the body's cells require zinc. Scientists believe that zinc plays a role in many diseases: for example, it helps package insulin in pancreas cells, and in people with type 2 diabetes, the gene that controls this packaging is often defective.

Previously, researchers used crude chemical techniques to get a rough idea of the concentration of zinc in cells. However, they could not produce an accurate picture of how much zinc was present in cells or where it was within them.

In today's study, researchers from Imperial College London and Eindhoven University of Technology in The Netherlands have developed a sensor using fluorescence proteins that act as a molecular switch by changing colour when they bind to zinc, showing how much zinc is present in an individual cell.

Professor Guy Rutter, one of the authors of the study from the Division of Medicine at Imperial College London, said: "There has been relatively little biological work done on zinc compared to other metals such as calcium and sodium, partly because we didn't have the tools to measure it accurately before now. Zinc is so important in the body - studies have suggested it has roles in many different areas, including muscles and the brain."

The new sensor, called a fluorescence resonance energy transfer (FRET)-based sensor, is made up of two color variants of a green fluorescent protein from jellyfish. The researchers altered the first variant to give off light at a certain wavelength, and altered the second variant to collect that light. When the proteins attached to zinc ions, they became pushed apart and the transfer of light between them became weaker. The researchers used a fluorescence microscope to detect the wavelengths of light emitted by the proteins. This revealed zinc in the cell, with coloured patches visible where the proteins detected zinc.

The researchers used their new sensor to look for zinc in pancreatic cells, where insulin is packaged around zinc ions. Previous research had suggested that in people with type 2 diabetes, the gene that controls the packaging process is often defective, affecting the way insulin is stored. The researchers found a high concentration of zinc ions inside certain parts of the cells where insulin is found. They hope their new sensor could help scientists look more closely at this to find out exactly how zinc is involved in diabetes.

Scientists believe zinc plays a role in diseases, including diabetes

"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. 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 also 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," added Professor Rutter.

The researchers would now like to develop their new sensor to look at zinc in a living mouse model, so they can observe the movement of zinc in different tissues, for example in diabetes.

The research in the UK was funded by The Wellcome Trust, Medical Research Council (UK) the EU and Imperial College London. The research of the Eindhoven group was funded by the Human Frontier of Science Program and the Eindhoven University of Technology.

-Ends-

For further information please contact:

Lucy Goodchild
Press Officer
Imperial College London
e-mail: lucy.goodchild@imperial.ac.uk
Telephone: +44 (0)20 7594 6702 or ext. 46702
Out of hours Duty Press Officer: +44 (0)7803 886 248

Notes to editors:

1. "Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis", Nature Methods, 30 August 2009.
Corresponding authors: Professor Guy Rutter, Imperial College London and Dr Maarten Merkx, Eindhoven University of Technology.
(For a full list of authors, please see paper)

2. About Imperial College London

Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 12,000 students and 6,000 staff of the highest international quality.

Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve health in the UK and globally, tackle climate change and develop clean and sustainable sources of energy.
Website: www.imperial.ac.uk

3. Eindhoven University of Technology (TU/e) is as a leading international university, with 7,000 students and 3,000 staff. The university specializes in engineering science & technology. It aims to play a prominent role at both national and international levels through its research and educational programs in the engineering science and technology domain. Its progress in the technical sciences contributes to the development of technological innovations and as a result to the growth of welfare and wellbeing of the world.

The TU/e is the university 'Where Innovation Starts'. In a recent ranking by the Leiden Centre for Science and Technology Studies, Eindhoven University of Technology ranked first of 350 best performing universities worldwide in regard to scientific output in cooperation with industry.

Website: www.tue.nl

4. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk

5. About the Medical Research Council The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public's needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk

6. About the Human Frontier of Science Program The HFSP supports novel, innovative and interdisciplinary basic research focused on the complex mechanisms of living organisms; topics range from molecular and cellular approaches to systems and cognitive neuroscience. A clear emphasis is placed on novel collaborations that bring biologists together with scientists from fields such as physics, mathematics, chemistry, computer science and engineering to focus on problems at the frontier of the life sciences. www.hfsp.org

Press office

Press Office
Communications and Public Affairs

Click to expand or contract

Contact details

Email: press.office@imperial.ac.uk