The Life Sciences Group operates/develops user platforms that aim to enhance the quality, scope and throughput of neutron scattering studies of the structure and dynamics of biological systems. Key issues of importance are deuterium labelling, which is of primary importance to small-angle neutron scattering (SANS) studies, neutron protein crystallography, elastic incoherent neutron scattering (EINS), and neutron reflection. Other important activities are the optimisation of sample preparation procedures, notably the crystallogensis requirements for large crystal.
The ability to exchange hydrogen by its heavier (and more strongly scattering) deuterium (2H or D) isotope in a way that is usually highly isomorphous offers a completely unique scope to neutron scattering studies of the structure and dynamics of biological systems in essential all relevant sample habits. Such a capability requires a range of in vivo and in vitro techniques that very difficult to maintain and develop at the laboratories of many user groups, given that the methods not easy to deploy on a one-off basis. They need continuity of expertise, economies of scale, and continuous methodology development that is driven by a combination of pressures from emerging new capabilities at the neutron facilities themselves as well as from the scientific priorities of the user communities that operate them.
The Deuteration Laboratory (D-Lab) is run as a user platform and is part of the Life Sciences Group. It allows users in the area of life sciences and structural biology to seek tailor-made deuterated biomolecules in support of neutron scattering (D22, D11), protein crystallopgraphy (LADI-III, D19), Dynamics (IN13, IN16) and reflectometry (D17, FIGARO). Access to the platform is by a rapid electronic peer-reviewed system. Applicants are encouraged to contact Dr. Michael Haertlein before submitting proposals to discuss technical feasibility.
Access to the deuteration laboratory is via a peer reviewed proposal system, with a panel of international experts nominated by the ILL Scientific Council. Further details are available from the Deuteration Laboratory website.
Note that acceptance of a proposal to use the deuteration lab facility does not imply automatic allocation of neutron beamtime although the beamtime committee will be informed of the outcome of the deuteration proposal.
Proposals for use of the laboratory should include:
- a description of the scientific case for using the laboratory
- an estimate of the time required and the costs of D2O and deuterated carbon sources
- an explanation of the background to the scientific problem and why the requirement for deuteration and in particular use of the ILL/EMBL facility is necessary
- a realistic estimate of the amount of time they need to use the laboratory.
For neutrons, the full exploitation of protein crystallography is still strongly restrained by crystal size. Given the fluxes available at the most powerful neutron sources, this will always be a major issue in delivering the huge potential that neutrons have for biological crystallography. By the very nature of crystallisation, there is no empirical reason why conditions cannot be identified that allow crystal growth to be extended; it is simply a matter of putting sufficient emphasis on rational approaches for the systematic exploration growth conditions in relation to the specific phase diagrams. This challenge has never been addressed properly since the inception of the field and it is instructive to reflect on the huge emphasis that the X-ray community has put on their crystallisation efforts over the last 20 years or so, and the rewards have been reaped. The crucial developments for macromolecular deuteration that have occurred in the recent past have resulted a reduction of the crystal volumes needed by a factor of ~10. This has had a very strong impact but further gains are needed if best use is to be made of the neutron crystallography instruments in Europe, both currently and in the future. Instruments such as LADI-III, D19 at ILL (Grenoble, France), and BIODIFF at FRM-II (Garching, Germany), are the best diffractometers of their type in the world, and with the approval of NMX at ESS (Lund) and plans for LMX at ISIS (Oxfordshire, UK) in the future, it is extremely important that the front end sample issue are addressed.
A project to support this priority has recently been funded by the European Commission HORIZON 2020 framework. The SINE2020 project and coodinated activities in this area are in progress at the Grenoble, Garching and Lund institutes.