Can Small Laboratories Do Structural Genomics?

Structural genomics centers have often been regarded as the “members only” clubs associated with expensive equipment, material, and personnel. Although much expense has been invested worldwide in structural genomics consortia, there has been an enormous amount of criticism on the apparent disproportional output produced relative to the amount of money spent. Here, we review and highlight some of the major achievements in structural genomics projects coupled to X-ray crystallography. Structural genomics has advanced technologies in high throughput bioinformatics, cloning and recombinant protein expression, crystal growth, and crystallographic structure determination. If cost can be reduced and feasibility increased then a modest-sized laboratory research group can significantly contribute to structural genomics efforts. We demonstrate this by examining a sequenced and annotated hyperthermophilic archaeal genome (about 2 million base pairs) with our own structural genomics methods. By incorporating proven strategies developed from large structural genomic centers with practical innovations, we have constructed a mini-pipeline in which a small group consisting of as few as two people can survey 1500 open reading frames for cloning, expression, crystallization, and structure determination for less than $200 000.