Thursday, 12 April 2018

A Visit to Diamond Light Source

Last February, a group of Birkbeck students were given the opportunity to visit the UK's synchrotron light source, Diamond, located near Didcot in Oxfordshire. Most of the students on the trip were taking the Techniques in Structural Biology (TSMB) course as part of a Master's degree. The majority were studying TSMB as a module of the face-to-face M.Sc. in Analytical Bioscience; one was on the distance-learning Structural Molecular Biology M.Sc and a few were studying Bio-Business (which does not include TSMB). This photo shows most of the group with Professor Nick Keep, director of the Structural Molecular Biology course and Dr Katherine Thompson, director of Analytical Bioscience, with part of Diamond's main building in the background.

Birkbeck staff and students in front of the 'doughnut' that houses the Diamond ring system

Dr David Price from Diamond gave the students a short lecture to introduce Diamond and the types of experiment that can be carried out there.

He explained that Diamond is a synchrotron radiation source, which means that it accelerates beams of electrons around the rim of a large doughnut-like structure so they reach speeds approaching that of light and give out extremely intense electromagnetic radiation in the form of X-rays 100 billion times more intense than the sun's rays. X-rays have wavelengths that range from 10-8 to 10-11 m, and those in the middle of this range, with wavelengths close to the length of inter-atomic bonds. These are ideally suited to probe the structure of matter on the molecular level, and they can do so in a lot of different ways.

Price explained briefly how a synchrotron radiation source works. Electrons are fired from an 'electron gun' into a linear accelerator and then into a small ring known as the booster synchrotron for further acceleration. They then enter the large storage ring, which has a circumference of about half a kilometre; it is this that gives the overall structure its doughnut-like shape. Strictly speaking, however, it is not a smooth ring but a polygon with 48 straight sections. The electron beam is bent by magnetism at each of its vertices, and it is this process that emits the intense X-rays. The X-rays produced at each vertex are emitted through a 'hole in the wall' at that vertex. They are then filtered and focused using complex optical equipment to give them the exact properties that are needed for a particular experiment. Each of these 'beamlines' is essentially a small laboratory with its own optics and analysis equipment and its own staff team. As the synchrotron structure has 48 vertices, there are 48 possible beamline stations, although they are not all operational at the same time. The Diamond website currently lists 31 operational beamlines, of which seven have been optimised for macromolecular X-ray crystallography. Some of the other techniques available are absorption and fluorescence spectroscopy and small-angle X-ray scattering.

There are more than 50 synchrotron radiation sources ('lightsources') in the world; Diamond is one of the more powerful and versatile of these, but it is the only one in the UK. Most - about 90% - of its users are academics who are required to publish their work in open access journals; over 1000 publications each year cite Diamond Academics apply for time on a specific beamline, and these applications are peer reviewed. About 10% of users come from industry and pay for access.

Price also highlighted briefly a few recent examples of research carried out at Diamond, focusing mainly but not exclusively on structural biology. These included the structure of a peptide hormone, GLP-1 (PDB 5NX2), that stimulates the secretion of insulin by beta cells in the pancreas and that could is an important target for drugs to treat type 2 diabetes. The structure of the EV71 virus (PDB 4CDQ), which causes the potentially fatal hand, foot and mouth disease, was solved at Diamond in 2012 and this is now being used to design potential drugs for this occasionally fatal disease. Away from structural biology - but not away from medicine - he described structural studies of metal alloys that can help understand why hip replacements can be rejected and inform the design of improved materials.

After the talk, the Birkbeck party was divided into two smaller groups to tour of the main site. Both groups visited one of the beamlines devoted to macromolecular X-ray crystallography, I24, where the structure of GLP-1 was solved. This beamline includes facilities for determining structures of viruses and membrane proteins, and for working with very small crystals (down to about 1.5 microns in diameter).

Looking down on a small part of the storage ring

Birkbeck staff (Prof. Nick Keep, far left and Dr. Clare Sansom, next left) and students in the control cabin of beamline I24, one of those used for macromolecular X-ray crystallography

The trip ended with a short visit to the UK's high-energy neutron and muon source, located on the same campus as Diamond and named ISIS after Oxford's river. These beams are also used to probe the structure of matter, using techniques such as neutron diffraction. We would like to thank all Diamond and ISIS staff involved for their contributions to a fascinating day.

PPS students will learn more about X-ray diffraction in the second-year module Techniques in Structural Molecular Biology (TSMB), and much more still if they choose to take the specialist Protein Crystallography course. And students on either course may get a chance to visit Diamond fir themselves, as we hope to run the trip again next year.

1 comment:

Kenneth A. Stover said...

Very enjoyable account of the outing. I wish I could've been there. Thanks for including photos of the group. Ken, PPS16.