The Oxford Protein Production Facility-UK

Proteins are essential components of all living cells. They comprise chains of amino acids coded for by specific DNA sequences and fold into three dimensional structures, that determine their function, for example as biological catalysts. Therefore, understanding protein structure and function is key to exploiting the information generated from sequencing of the human genome and in particular those of many human pathogens. Knowledge of individual proteins has made a major contribution to the development of a number of important drugs, e.g. Zanamivir (influenza neuraminidase inhibitor), Lapatinib (kinase inhibitor), Darunavir (HIV protease inhibitor). However, high throughput DNA sequencing continues to add to the database of known proteins at a rate that far exceeds our capacity to decipher their function. Therefore, accelerating the production of recombinant proteins is key to closing the gap between the acquisition of protein sequences and the determination of their structure and function. In response to this challenge, the Oxford Protein Production Facility will provide infrastructure to underpin the study of proteins on different length and time scales from atomic resolution (x-ray crystallography) to whole cell systems (optical microscopy).

The Oxford Protein Production Facility-UK (OPPF-UK) is a National resource for protein science. The overall goal of the OPPF-UK is to provide the UK biological, chemical and biomedical communities with a world-class facility for the production of proteins for structural and functional research. The OPPF-UK has established a high throughput approach to the production of recombinant proteins using three main expression hosts (E. coli, mammalian cells and baculovirus/insect cells) which is provided as a service to the UK scientific community through a peer-review process. Research and development in the OPPF-UK will be focussed on streamlining the cloning, expression and purification of multi-protein complexes and membrane proteins using insect and mammalian cells. Methods will be rolled out as part of the user programme of the OPPF-UK. In parallel, data management systems will be enhanced to provide users with secure on-line access to all project data.

Recombinant proteins play a key part in the drug discovery process, for example as components of biochemical screens for new chemical entities (NCEs), antigens for raising therapeutic antibodies and for crystallization to obtain structural information. We are contributing to projects involving the structure-based identification of NCEs, for example inhibitors of a novel metallo-beta-lactamase (NDM-1) which has been implicated in widespread antibiotic resistance of important bacterial pathogens. New knowledge will be added from these studies which may ultimately help in the development of new drugs. The OPPF-UK is developing a number of direct links with the biotech/pharma sector through consultancy and training and as a provider of protein production services. The OPPF-UK is also actively involved in helping to educate the next generation of potential research scientists. We contribute to school visits to the Rutherford Appleton Laboratory through staff giving talks about how proteins are studied in the OPPF-UK and our links with the Diamond Light Source. Finally, the OPPF-UK provides an important opportunity for staff development, since working in the OPPF-UK involves scientists in the management of multiple projects, dealing with deadlines and liaising with external users. This experience helps to develop transferable skills that are highly applicable not only to jobs in research & development but also other professions outside of science.