Public Release: 

University of Manchester uses crystals to help battle deadly diseases

University of Manchester

A groundbreaking technique developed at The University of Manchester, which uses crystals to map 'invisible' parts of molecules, is set to revolutionise drug discovery.

The technique, which involves sending beams of neutrons through crystals at freezing temperatures, just a few degrees above 'absolute zero', will for the first time allow scientists to see complete structures of protein molecules, right down to the last atom.

The problem faced by scientists using current methods is the fact that it is not possible to detect every atom in a protein's molecular structure, and the structures therefore are incomplete - making drug design more difficult.

Professor John R. Helliwell, Professor of Structural Chemistry, who led the research, said: "This has raised the stakes in the world of drug discovery. This methodology will make research in the field more powerful, more effective and more efficient."

The breakthrough allows the molecular structures of proteins, the chemical catalysts in the body, to be studied in complete detail. In fact, experiments at the University have shown that the number of visible atoms in a molecule doubled when using the technique, compared to techniques used today.

Protein Crystallography is an important tool used to determine the three-dimensional structures of proteins. Once a pharmaceutical company has this information, it is able to tailor drugs to target specific proteins, eg interfering with the function of such proteins in infectious agents like tuberculosis - enabling the production of more effective medicines.

'Ultra-Cold Neutron Protein Crystallography' improves on current methods by probing protein structures with neutrons at temperatures of 15K (-258 degrees C), dramatically increasing the number of visible atoms. The process especially reveals the hydrogen atoms, which hold the key to many chemical reactions, and because of their low mass, are rarely revealed by current methods like X-Ray Crystallography even if carried out at freezing temperatures.

Professor Helliwell added: "As well as the above advantages this makes other classes of experiments on proteins feasible. In particular, the comparison of protein structures at ultra-cold versus room temperature allows the details of atomic vibrations to be separated from structural disorders."

"Another benefit to research that now becomes possible is that chemical reactions can be set running directly in the crystal and then freeze-trapped so as to probe the proteins in time with the neutron beam whilst the protein is actually in its functional state."


Notes to editors:

  • Release based on research paper: "The 15-K Neutron Structure of Saccharide Free Concanavalin A" to be published on November 23rd 2004 in the scientific journal 'Proceedings of the National Academy of Sciences' (USA). Authors: M P Blakeley, A J Kalb (Gilboa), J R Helliwell & D A A Myles. The work is also highlighted by PNAS in one of their Research Commentaries in the same issue and has been selected for reviewed by the journal Nature in their Research Highlights' November 18th issue page 288.

  • The University of Manchester collaborated with the following institutes:- in Grenoble, France, the neutron research facility of the Institut Laue Langevin and also the Grenoble Outstation of the European Molecular Biology Laboratory (EMBL), and finally with The Weizmann Institute in Israel.

  • Dr M Blakeley is an honours graduate in chemistry from the University of Manchester and his Structural Chemistry PhD thesis project was under the supervision of Prof Helliwell. Dr Blakeley's thesis work in Grenoble was then jointly supervised by Dr D A A Myles of the EMBL. We thank the EPSRC for this PhD research studentship jointly funded with the Institut Laue Langevin.

    * Related references:-
    M P Blakeley, M Cianci, J R Helliwell and P J Rizkallah "Synchrotron and neutron techniques in biological crystallography" Chem Soc Reviews (2004) 548-557.
    J Raftery and J R Helliwell "Spoilt for choice: protein target selection in a time of plenty" (2002) Acta Cryst D58, 875-877.

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