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SPINE – strengthening structural biology

The SPINE project aims to speed up the structural determination of proteins important for human health through the development of high-throughput technologies. Linking protein structure to function is an essential step in the identification of potential targets for new drugs and understanding disease processes. The project has already made a vital contribution to the structure determination of a protein from the SARS (Severe Acute Respiratory Syndrome) coronavirus.[1] [2]

SARS coronavirus nsp9 replicase protein

SARS coronavirus nsp9 replicase protein

SPINE’s targets are proteins from bacterial pathogens, such as Mycobacter tuberculosis, viral pathogens such as Herpesviridae, and human protein families, particularly those relevant to cancer and neuro-degenerative diseases. Selected proteins are targeted for their roles in pathogenic virulence or because they are potential drug targets. The pharmaceutical and biotechnology industries are closely involved in this project to ensure that results are quickly transferable and have a real impact on human health.

Pooling resources

Determining protein structure is a lengthy and costly process requiring large-scale equipment for X-ray crystallography and nuclear magnetic resonance, complex infrastructure, and multidisciplinary expertise. The SPINE project is harnessing European expertise and resources in structural biology – 20 partners in seven countries – to achieve what no single partner can do alone. Each step of the structure determination process, from target selection, to protein production, purification, crystallisation and structure analysis, is being optimised to increase throughput. For example, the crystallisation stage, a vital precursor to X-ray analysis of the protein’s 3D structure, is being automated by the use of extreme precision robotics.

A key partner in the project is the European Bioinformatics Institute, bringing expertise in software-based target selection. The EBI also tracks and disseminates the status of SPINE targets to ensure that results are distributed rapidly and efficiently worldwide.

The combination of bioinformatics and knowledge gained from high-throughput technologies makes suitable target proteins easier to select – the ‘low-hanging fruit’ approach. This new collaborative approach means that researchers can react quickly to urgent scientific challenges. The SARS protein structure – a protein which plays a key role in replication of the virus – was solved just six months after the virus was identified.

Project coordinator:
Professor David Stuart
Division of Structural Biology
Oxford University, UK

1. Structure (12) 341, February 2004
2. Proceedings of the National Academy of Sciences (11), 16 March 2004

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