A UK National Protein Production Facility for Biomedically Driven Structural Proteomics

Lead Research Organisation: University of Oxford
Department Name: Medical Sciences Division

Abstract

The human genome project, over some 10-15 years, has advanced by many orders of magnitude DNA sequencing and the manipulation and management of large biological data bases. The resulting sequence of the human genome has been hailed as an epoch making achievement ushering in as yet largely uncharted opportunities for advances in human healthcare. At a pragmatic level it is generally accepted that such advances can only occur when the genomic information is complemented by advances in our understanding of protein function. A full functional description of a protein requires knowledge of its 3D structure, often as part of a large multi-molecular assembly, but the rate of determination of genomic sequences has far outstripped that of structure determination. The aim of the Oxford Protein Production Facility - UK (OPPF-UK) is to facilitate this process by developing high throughput tools for the over-expression and structure solution of human proteins and proteins from human pathogens. In the pilot phase the project has assembled a pipeline for protein production involving sophisticated data management and robotic technologies in several areas. These technologies are highly effective for proteins from bacterial pathogens and the challenge now is to refine these technologies to increase their effectiveness for human and viral proteins. Target selection will involve choosing areas where problems of biomedical importance can be advanced more effectively than by the application of standard laboratory methods. The intention is to mesh with well established networks of interdisciplinary research covering molecular, cellular and clinical studies. The OPPF-UK will form part of a multi-disciplinary Research Centre to be built adjacent to the Diamond Light Source, the UK?s new synchrotron research facility. The OPPF-UK will part of a unique environment bringing together biological, physical and material sciences.

Technical Summary

The overall goal of the OPPF-UK will be to provide the UK with a world-class facility for the production of proteins for structural and functional proteomics. The aims of the Project are : (1) to provide high quality facilities, intellectual input and a broad knowledge base to users, (2) to initiate collaborative research projects and stimulate multi-disciplinary interactions, both locally at RAL/ Diamond, nationally and internationally, (3) to lead technology innovation for the production of proteins of relevence to human and animal health, responding to the development requirements of users and (4) to train and educate the UK community in the applications and technology, transfering technology to industry and academia.

Publications

10 25 50
 
Title CLONING 
Description VARIOUS EXPRESSION VECTORS PRODUCED AND ANTIBODY PRODUCTION METHOD ESTABLISHED (SEE PATHOLOGY CALLABORATION FOR LATTER). 
Type Of Material Technology assay or reagent 
Year Produced 2007 
Provided To Others? Yes  
Impact 18988019 18662785 17317681 ABOVE ARE PUBMED IDS FOR METHODS PAPERS. VECTORS HAVE LED TO MANY RESULTS PAPERS, WHICH I DON'T HAVE DETAILS OF. 
URL http://europepmc.org/abstract/MED/18988021
 
Description Baculovirus 
Organisation University of Reading
Department School of Animal and Microbial Sciences Reading
Country United Kingdom 
Sector Academic/University 
PI Contribution Protein production, structure
Collaborator Contribution Joint results and patent
Impact Paper with Ian Jones in NSMB
Start Year 2006
 
Description Fab Cloning and Expression 
Organisation University of Oxford
Department Sir William Dunn School of Pathology
Country United Kingdom 
Sector Academic/University 
PI Contribution We have introduced a generic method for the production of antibody fragments
Collaborator Contribution Joint development
Impact Methods reported in 18662785 and Methods in Molecular Biology (in press)
Start Year 2006
 
Description Insect Cell Expression 
Organisation Oxford Brookes University
Department School of Life Sciences Oxford Brookes
Country United Kingdom 
Sector Academic/University 
PI Contribution Testing and developing methods with Professor Linda King (Oxford Brookes University and Oxford Expression Technology Ltd)..
Collaborator Contribution Help in developing methods for insect cell expression
Impact Three publications in peer-reviewed journals: 19655260, 18781697, 20441568
 
Description Vaccinia 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Protein production, structure determination
Collaborator Contribution Numerous joint publications
Impact Various publication with G Smith in author list.
Start Year 2006
 
Description Virus evolution 
Organisation University of Helsinki
Country Finland 
Sector Academic/University 
PI Contribution Structure determination
Collaborator Contribution Numerous publications and joint avtivity
Impact A number of the publications fall in this category. These have Bamford as co-author
 
Description penicillin binding proteins 
Organisation University of Dundee
Department Biological Chemistry and Drug Discovery (BCDD)
Country United Kingdom 
Sector Academic/University 
PI Contribution protein production and structure determination
Collaborator Contribution Identification of inhibitors
Impact first results reported in 20974151
Start Year 2009
 
Title pOPIN vectors 
Description vectors produced and distribted via MTAs. 
IP Reference  
Protection Protection not required
Year Protection Granted
Licensed No
Impact Various structures