International team wins £1m research grant

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Posted on 12 May 2017

Keele University is part of an international collaboration which has received a prestigious research grant for imaging single molecules.

Keele University’s Professor Trevor Forsyth is part of the team that has been awarded a £1 million research grant by the Human Frontier Science Program (HFSP) to develop a novel method for imaging individual biomolecules with atomic resolution.

Professor Forsyth, who is currently seconded to the Institut Laue-Langevin (ILL) in Grenoble, France, makes wide use of neutron and X-ray beam central facilities for the study of biological macromolecules. The HFSP award will allow Professor Forsyth to provide a Keele link from the Grenoble site to the one of the most important European facility developments in a generation – the creation of an X-ray laser source.

“This award brings together a remarkable range of institutes and expertise, and provides linkage with other facilities that offer highly complementary information. The ILL is the most intense neutron source in the world and is part of the Partnership for Structural Biology (PSB) on the Grenoble EPN site, which provides a formidable range of technology platforms that service interdisciplinary and integrated approaches for the study of important problems in the life sciences” said Professor Forsyth, who is a professor of biophysics at Keele and works within the PSB.

The collaboration also includes Henry Chapman from Hamburg/DESY (Germany), Ned Seeman from New York University (USA), and Rick Millane from the University of Canterbury (New Zealand).

The intercontinental collaboration is addressing the challenge of imaging single macromolecules with X-ray free-electron lasers (XFELs), strongly complementing ongoing neutron and X-ray approaches. These devices, driven by powerful particle accelerators, produce incredibly bright and short pulses of X-rays that can reveal the spatial structure of molecules with atomic resolution. Currently, this sort of investigation requires scientists to crystallise the molecules first. The tiny crystals diffract the X-rays, and from that diffraction pattern the molecule’s structure can be calculated.

However, growing crystals from biomolecules – especially those of particular interest to science –is often a painstaking process and sometimes not possible at all. A method to image biological macromolecules without having to crystallise them would be a significant advance to the field. The team aims to engineer samples in a general way to make it easier to measure diffraction signals from them, and to interpret the signals. To this end, an extra structure will be added to each molecule that can act as a holographic reference to correctly interpret and combine diffraction data from many such particles.

The team have already been collaborating on amyloid type structures using the Stanford XFEL in California, extending results obtained using neutron and synchrotron beam sources. At Keele, the work has also been driven by Dr. Estelle Mossou (Keele PhD 2010, now based at ILL and a Keele Honorary Senior Lecturer).

The Human Frontier Science Program aims to promote intercontinental collaboration and training in cutting-edge, interdisciplinary research focused on the life sciences. Out of this year’s 1073 proposals, only 30 projects were chosen for a grant.

The international Human Frontier Science Program Organization (HFSPO) is based in Strasbourg, France, and receives financial support from the governments or research councils of Australia, Canada, France, Germany, India, Italy, Japan, Republic of Korea, New Zealand, Norway, Singapore, Switzerland, the UK, the USA, as well as from the European Union.