Improvements on the big tube

November 20, 1998

A Pounds 175 million synchrotron could put Britain at the forefront of genome research, reports Julia Hinde.

The comprehensive spending review brought a smile to the faces of scientists the country over. After years of doom and gloom, science and research received a Pounds 1.4 billion boost.

The allocation included Pounds 145 million for a new synchrotron source - Pounds 110 million from the Wellcome Trust and Pounds 35 million from the government - to replace the world's first such dedicated source at Daresbury in Cheshire. This, according to the Wellcome Trust, is "nearing obsolescence", and according to science minister Lord Sainsbury, replacing it was "one of our highest priorities in the CSR".

The source will be 10,000 times brighter than the existing machine, which should allow the structure of proteins to be determined considerably more quickly. Such an advance is particularly significant in the light of the current push to sequence the human genome, which should expose an increasing number of new, potentially interesting proteins.

But how will it work?

A synchrotron accelerates electrons around a long, narrow steel circular tube. The electrons, accelerated almost to the speed of light, change direction under the influence of a magnetic field as they travel around the tube. This change in direction generates more energy but, unable to travel any faster, the electrons instead produce light, in ranges from infrared to X-rays.

The high-energy X-rays produced through this process are channelled from the synchrotron to form beam lines that, when shone onto proteins or even a section of tissue, scatter in ways dependent on the material. The change in pattern allows scientists to begin to understand the structure of the material under observation. This approach, called X-ray crystallography, has been used to investigate the complex molecular structures within important proteins.

The synchrotron source, used by structural biologists and material and physical scientists among others, also allows techniques such as spectroscopy (where electrons are displaced from a material as it is bombarded by the light source, revealing information on the structure of the underlying material) and microscopy (where ultraviolet light allows fluorescent markers to be followed through living systems). Materials scientists working on everything from steel to electronics use synchrotron radiation.

But it is the sequencing of the human genome and the potential it generates for new understanding, and ultimately for drug development, that appears to have provided the momentum - and the cash - for the new synchrotron source.

Wellcome is at the forefront of the worldwide quest to identify the genetic make-up of the body, the human genome.

Genes code for proteins. To exploit our knowledge of the human genome requires understanding of the structure of these proteins. For example, a particular disease might be found to be caused by excess production of a specific protein. If the structure of that protein was understood, a new medicine could potentially be designed to lock onto the protein and prevent its growth.

A spokesman for the Daresbury sychrotron source said it was unsuitable for genome research. "The one we want to build will have more juice," he explained. "This means that the time the protein needs to be exposed to the X-ray beam will be reduced, allowing very accurate pictures to be taken in a shorter time and possibly reduce X-ray damage."

The new source, as well as shining light on complex structures, should speed up work at a time when a backlog of potentially interesting proteins is building up.

The exact specification of the source, hoped to be operating by 2005, and its location are still to be decided. The Daresbury machine is 96 metres in circumference: the new one will be nearer 300 metres. A joint Wellcome Trust/Office of Science and Technology group is appraising the options.

"We are determined to get it right," director of the Wellcome Trust, Michael Dexter, told a recent House of Commons science and technology committee. He denied the committee was right in its concern that Wellcome's financial involvement may result in the new source being reserved solely for biomedical use.

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