Diamond’s latest beamline to further Alzheimer’s disease studies

A team of scientists from the University of Reading became the first researchers to use the UK’s national synchrotron facility’s latest experimental station (B23). Designed for experiments requiring circular dichroism (CD), a technique which allows the study of biological structures which do not readily form crystals, Diamond’s 13^th beamline will benefit the chemical and life sciences; enabling the investigation and observation of structural and dynamic interactions of molecules such as proteins, nucleic acids and small chiral molecules.

Prof. Ian Hamley, the head of Physical Chemistry at the University of Reading and a Diamond Professor, and his team used B23 to further their studies into the cause of diseases such as Alzheimer’s and CJD.

Front, from left to right: Claire Moulton, Ian Hamley, Gemma Newby, Giuliano Siligardi, Back, from left to right: Daniel Myatt, Tamas Javorfi.

One of the main contributing causes of Alzheimer’s disease and CJD is thought to be the formation of hard, insoluble plaques between the neurons in the brain. In a healthy brain, protein fragments including the so-called amyloid beta protein are broken down and eliminated but in the case of Alzheimer’s disease and CJD, these structural protein fragments (fibrils) accumulate to form troublesome amyloid plaques.

Prof. Hamley and his team have synthesised samples of short peptides (fragments of proteins), based on the human sequence, modifying their design with the aim of enabling them to bind to the fibrils in the brain and disrupt the formation of plaques. The team used Diamond’s B23 beamline for circular dichroism to investigate the structure of the short peptides – an essential step in their research; without knowing the structure of the synthesised protein fragments, the group cannot determine how they function.

CD spectroscopy is the technique of choice to characterise and investigate the structural properties of chiral materials, like peptides, proteins, sugars, lipids and many drugs. Commercial lab-based CD instruments are available to do similar studies, but B23 offers the great advantages of a synchrotron source – high flux (with a spectral range of 140 – 700 nm), a small beam, in this case about 0.7x2 mm at the sample and a team with 15 years of research experience in the field. The high brightness of UV light on Diamond’s CD beamline allowed Prof. Hamley to achieve fast measurements with good signal to noise ratio.

Speaking about his time on B23, Prof. Hamley says, "It was excellent to be the first team to use Diamond’s circular dichroism beamline. We were able to do everything we needed to do and collected some good results." Armed with the data collected at Diamond, Prof. Hamley and co. are now able to move on with their studies with the long term goal of inhibiting the formation of amyloid plaques relevant to the development of treatments for diseases such as Alzheimer’s and CJD.

Over the next six to nine months, B23 will continue to accept a small number of experienced users who will help to commission the beamline. Dr Giuliano Siligardi, Principal Beamline Scientist for B23, aims not just to provide a UK CD facility but to push the technique to new boundaries. "In future it might be possible to extract 3D information from CD measurements in solution," he says, describing the simulation of CD spectra of molecular structures that can be calculated by quantum-mechanics modelling although still at high computing cost. "If the simulated spectrum resembles/coincides with the measured spectrum, it’s very likely they represent the same structure. Recently this approach has been done for a small peptide molecule of about 10 amino acid residues. It is conceivable that in 10-15 years it will be possible to do the same with larger molecules like proteins with hundreds of residues at a reasonable and affordable cost."

B23 is part of the second phase of construction at Diamond which is due to be complete in 2012. The further 9 Phase II beamlines that are scheduled to be added over the next three years will bring the total of operational beamlines at Diamond to 22, covering a wide range of science; from biology and medicine, to the physical and chemical sciences, through to the environmental and engineering.

More information on Diamond’s circular dichroism beamline.

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For more information or images, contact:

Sarah Bucknall at Diamond: 0044 (0) 1235 778639 / 07920 296957 / sarah.bucknall@diamond.ac.uk