Grant Details
A NW structure genomics centre (NWSGC) is proposed which exploits the strength of ten groups from a number of NW-Universities, a major pharmaceutical industry (AstraZeneca) and Daresbury Laboratory as well as the unique resource offered by the close proximity to the only synchrotron radiation source in the UK. Our aim is to develop the infrastructure and facilities at the Laboratory to provide a high throughput crystallographic structure determination of proteins in a number of pathogens with the ultimate aim of improving our understanding of host-pathogen interactions leading to more effective drugs. Immediate funding has been approved by the Smith review for a NWSGC's dedicated MAD beam line on a multipole wiggler (£2.65M includes a scientist) on the SRS. This will provide a world competitive MAD facility in the UK for several years.
We also propose to continue to seek funding to build the following high throughput facilities at Daresbury as part of our high throughput structure genomics effort: a protein production factory and a robotic based crystallisation laboratory.
Tuberculosis Drug Development
Tuberculosis (TB) continues to be a major global health problem. Compliance with the lengthy and complex regimen of chemotherapy is poor and treatment failure is common. Adding to the problem, multi-drug resistant strains of Mycobacterium tuberculosis have emerged. TB drug research was neglected for several decades. The aim of this Integrated Project is to generate high quality lead compounds with potential to be developed into the next generation of medicines for the treatment of tuberculosis. By bringing together research scientists from many different disciplines, a fully integrated approach will be taken to the identification, characterisation and optimisation of compounds possessing activity against Mycobacterium tuberculosis in models of infection. This programme will exploit recent advances in our knowledge of the pathogen revealed in its genome sequence and translate basic research findings into practical applications.
Structural Genomics of Metalloproteins 'Function and Mis-function'
SGEMET aims to mobilise European research groups involved with 'age-related' disease, metalloproteins structure-function research and high throughput structural determination approaches (technical as well as methodoligical). Through this integration of effort across Europe of some 12 major institutions (50 PIs with over 300 scientists) SGEMET will strengthen the European competitiveness in Structural Genomics and address one of the most socially relevant health issue of 'age-related diseases'. Metalloproteins are involved in many disease states including ageing processes and are a special class of proteins that are thought to make up ~30% of the genome and are not being addressed specifically in the current high throughput programmes worldwide. Special approaches are needed for structural genomics study of these proteins.