Division of Structural Biology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, England, and York Structural Biology Laboratory, Department of Chemistry, University of York, York YO10 5YW, England The concept of structural genomics arose in the mid to late 1990s in the USA and Japan as a response to the success of high-throughput (HTP) sequencing methods applied to whole genomes (see http://www.isgo.org). It was imagined that similar HTP methods could be applied to obtain three-dimensional structures of all the proteins (the ‘proteome’) of an organism, which would in particular be an efficient way of filling in the gaps in observed ‘fold-space’. This vision led to the investment of substantial sums of money into large-scale structural genomics projects in the USA [e.g. nine projects funded by the NIH/NIGMS Protein Structure Initiative (PSI) from September 2000 to June 2005, http://www.nigms.nih.gov/psi/] and Japan (e.g. the massive RIKEN project, http:// www.rsgi.riken.go.jp/). These were characterized by the concentration of resources into a small number of large centres, the development of novel, automated technologies to permit a HTP pipeline approach to structure determination, and a focus on novel folds as the major target criteria. The US-based projects, in addition, required immediate public deposition of structural data whereas the Japanese RIKEN project also aimed to support Japanese industry, precluding deposition in advance of patent evaluation. Europe was slower in implementing HTP approaches to structural biology. The Protein Structure Factory in Berlin, Germany (http://www.proteinstrukturfabrik.de/) led the way, followed by the Oxford Protein Production Facility (OPPF) in Oxford, UK (http:// www.oppf.ox.ac.uk/) and the Genopoles in France (notably Gif, Marseille and Strasbourg, http://rng.cnrg.fr/). However, it was not until October 2002 that the first Europe-wide project began. This was a three-year project funded by the EU FP5 programme called SPINE: Structural Proteomics IN Europe (http://www.spineurope.org). SPINE, a ‘second generation’ structural genomics project (indeed purposefully called a Structural Proteomics project to draw a distinction), made some radical departures from the firstgeneration initiatives, while at the same time obviously benefiting from the experience and technology development of the preceding projects. The challenge set for SPINE was to push forward with cutting-edge technologies aimed at biomedically relevant targets at the same time as generating a pan-European integration on biomedically focused structural proteomics. The SPINE consortium comprised