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Lasers, gold and atomic forces as physics helps our understanding of diseases

Studying the early stages of Alzheimer's or heart disease is not research you'd expect to find in a physics laboratory. But at Leeds, equipment more commonly used to study the physical properties of metals or other inorganic material is enabling scientists to 'see' the toxic structures formed in the brain of Alzheimer's sufferers, or watch the molecular interactions as a blood clot forms.

With £1.7m from the HEFCE’s science research infrastructure fund (SRIF), Leeds’ new biophysics research laboratories are now unrivalled in the UK, with state-of the-art equipment opening up exciting new areas of research around a key theme in the University’s research agenda: the interface between the physical and life sciences.

Biophysics uses physical principles to gain new insights into biology, and at Leeds strong links have been made between the department of physics and astronomy and researchers in the life sciences looking at the causes and properties of human diseases.

Three main facilities have been developed: a laboratory equipped with six atomic force microscopes (AFMs), one unique in the UK; a new laser laboratory; and a surface science laboratory. Dr Alastair Smith, who led the bid for SRIF funding with Professor Sheena Radford, is pleased with how the project has progressed.

Making light work – Chris Gell (top) with the new laser equipment and (above) Alastair Smith and Sheena Radford with the atomic force microsopes

"Better facilities enable more extensive collaboration and internationally competitive research,” he said. “We’re opening up collaborative possibilities with biochemists and clinical researchers within this University and with other institutions as well. Earlier this month we hosted the first joint UK/Japan biophysics workshop, funded through the BBSRC.”

Each facility has a resource manager who will, alongside their own research, train and support academics from other disciplines to use the new equipment.

Resource manager for the atomic force microscopes, Dr Simon Connell, explains the equipment’s capabilities: “These microscopes provide a three-dimensional image of a surface at an incredibly high resolution. As well as showing height and depth, the microscope can measure magnetic, molecular or electrostatic forces. One of our microscopes – unique in the UK – is integrated with an optical microscope to allow researchers in cell biology to locate areas of interest in large samples, and then zoom in at very high resolution.”

Dr Connell (right) is partly funded by leading manufacturer of AFMs, VEECO. Head of molecular vascular medicine, Professor Peter Grant is using the equipment to study blood clot formation.

"Our interest is in fibrin, from which clots are formed,” said Professor Grant. “The AFM has allowed us to see the growth of fibrin at a molecular level in real time – the first time anyone has been able to ‘watch’ a clot form. Understanding how and why fibrin forms will help our understanding of the causes of heart disease and strokes."

Using the AFMs, senior lecturer in pathology Dr Leslie Bridges is also able to watch the formation of the material he’s studying: the toxic fragment of a protein which kills brain cells in Alzheimer’s sufferers.
“Abnormal metabolism associated with Alzheimer’s disease causes proteins in the brain to form as fibrils,” said Dr Bridges. “These are toxic to healthy cells. Under the AFMs, we can ‘grow’ fibrils, watch as they form, and can introduce drugs or change conditions to see what inhibits their production. It’s a first step towards finding possible treatments for the disease.”

Dr Steve Evans’ biophysics research is gold-plated. His team are studying the intricate signalling systems at the cell membranes which regulate cellular activity, and to do this they attach cell membranes to gold or silicon surfaces.

“The gold or silicon acts as an electrode so signals can be measured,” said Dr Evans (left). “Cell membranes and the proteins active within them are vitally important for how the body recognises disease, or hormones. It’s very difficult in the laboratory to make them function as they would in normal biological conditions, but in our system they do.”

Most of our senses are linked to these proteins, and Dr Evans believes his research could lead to biotechnology which has the ability to touch, taste, see or smell. It could also be used for medical trials of new drug treatments.

The third area of new expertise which the SRIF funding has opened up is in laser spectroscopy. Chris Gell is the resource manager for this facility, now among the best in the country for studying structural molecular biology.

“The lasers enable us to analyse biological structure in great detail, and measure biological events which happen very quickly, but at what can be a crucial moment in cell development,” said Chris Gell. “For example, using the laser, we can monitor the ultra-fast interaction between proteins and nucleic acids which normally takes place within a cell, but which is a critical step in the reading of the genetic codes.”

“Much of our research within biophysics takes place at the level of single molecules,” said Professor Radford. “It’s often incorrect behaviour at the molecular level which is the cause of disease, but conventional experiments use concentrated solutions, studying billions of molecules simultaneously. This provides an average result which can mask minute, but important, differences between molecules behaving correctly and those that can cause disease.”

The biophysics refurbishment is part of £49m SRIF funding to support scientific research at the University.


Dr Simon Connell will take up his post as SRIF SPM manager on 15 January 2003. He is currently involved in a collaboratoive project between Dr Smith's group in physics and astronomy and the oral biology in the Leeds Dental Institute funded though an MRC ROPA grant.


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