Details of Grant

EPSRC Reference:

GR/R99393/01

Title:

Deuteration initiative for biological neutron scattering and nmr

Principal Investigator:

Other Investigators:

Barlow, Dr D	Forsyth, Professor T	Lawrence, Professor MJ
Isaacs, Professor NW	Watts, Professor A	Cooper, Professor J
Perham, Professor RN	Kneale, Professor G	Byron, Professor O

Researcher Co-Investigators:

Dr M Myles

Dr P Timmins

Project Partners:

Institut Laue-Langevin

Department:

Sch of Chemistry & Physics

Organisation:

Keele University

Scheme:

Standard Research (Pre-FEC)

Starts:

01 January 2003

Ends:

30 June 2006

Value (£):

800,878

EPSRC Research Topic Classifications:

Biological & Medicinal Chem.	Chemical Biology
Chemical Structure

EPSRC Industrial Sector Classifications:

No relevance to Underpinning Sectors

Related Grants:

Panel History:

Summary on Grant Application Form

A consortium of UK researchers, in collaboration with Grenoble staff, will undertake a number of well-defined projects of high biological interest. Each project will use neutron scattering/NMR methods to obtain unique structural information. Deuterium labelling is central to each project and each will exploit the capacity of a new deuteration laboratory within the ILUEMBL at Grenoble. This laboratory, which has strong core funding from the ILL, has just been awarded a major EU RTD grant for the development of deuteration techniques and is now an obvious base for the work we propose. The specific project objectives are summarised below:(a) Hydration gattems in homopolvmer sequences of A-DNA (Forsyth, Fuller)(b) Neutron fibre diffraction studies of amyloidogenic Deptide sequences from the adenovirus fibre (Forsyth, in collaboration with A. Mitraki. IBS Grenoble .(c) Fibre diffraction studies of fd and Pf1 filamentous bacteriophage using selective deuteration (Perham, Marvin, Forsyth). (d) Crystallographic studies of the interaction between integral membrane proteins and lipids (Isaacs, M yl es) (e) Crystallographic and NMR studies of endothiapepsin in complex with a number of difluoroketone inhibitors (Cooper. Myles) (f) Neutron structure analysis of an eye-lens protein (Myles, Timmins, in collaboration with P. Lindley, ESRF, and C. Slingsby. Birkbeck) (g) SANS studies of molecular complexes triggered in response to nematode protein ES-62 (Byron, Timmins). (h) SANS and neutron reflectivity studies of the epitheleal tight 'unction protein occludin (Barlow. Lawrence. Timmins). (i) SANS and NMR studies of the subunit structure of type I restriction-modification (R-M) enzymes (Kneale. Timmins). Scientific activity linking biological applications at Grenoble with Oxford University facilities at the Rutherford Appleton Laboratory (RAL) in the UK will be developed. A major objective is to expand good scientific interaction between the UK science programmes at ILL and RAL. The involvement of Professor A. Watts in this application is therefore highly significant. As a Senior Scientist at ISIS, and as Director of the National Biological Solid State NMR Facility, his group will interact with staff at the ILL deuteration laboratory to facilitate exchange of expertise between the two facilities and to provide a connection between ISIS users and the deuteration laboratory. Staff in his group at RAL and at Oxford University will, in collaboration with staff at the ILUEMBL, develop novel labelling methods of particular interest to solid state NMR. The interaction between Oxford/RAL/ILUEMBL is also a key element of the EU RTD award for the development of deuteration techniques and will further consolidate this objective. A science-led programme within the deuteration laboratory in support of biological neutron scattering and NMR will be initiated. The aim of the deuteration laboratory itself is to provide users with the facilities and expertise that will enable them to produce deuterated macromolecules on a far more routine basis than is currently possible. The cost of running this facility on a ' per project ' basis is relatively modest, and it will pay large dividends in the quality and scope of the biological work that it enables. Quite apart from their own scientific merits, the UK-based projects we propose here will also stimulate a science-led ethos and in-house activity within the laboratory that we believe will make a crucial contribution to effective user support. This objective will again be strongly reinforced by the activity arising from the EU RTD project.

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Project URL:

Further Information:

Organisation Website:

http://www.keele.ac.uk