BIOXHIT, which stands for "Biocrystallography on a Highly Integrated Technology platform" for European structural genomics, brings together 27 partners, including all of Europe's synchrotrons, from nine different countries. BIOXHIT will build three-dimensional architectural models of biological molecules, without which, it is currently impossible to comprehend how proteins and other molecules operate in cells, or to design new drugs that will affect their functions.
The goal is to take the best of current technologies at major European centres for research in structural biology, develop them further and weave them into a single platform that integrates and standardises the best of current technology, and spread it throughout Europe. EMBL-Hamburg will co-ordinate the integrated project. BIOXHIT combines a strongly focused research programme with networking, training and mobility of staff under a single and efficient management structure.
The most common method for obtaining three-dimensional models is to bombard crystallised proteins with high-powered Xrays generated at huge synchrotron facilities. "We already have all the single components necessary to solve molecular structures", stated Victor Lamzin, grant co-ordinator at EMBL-Hamburg. "We have synchrotrons, we can grow protein crystals, we have the software components and we can obtain structures. But the tools we use were not originally designed for high-throughput work. This is what is needed now because of the tens of thousands of new molecules we have discovered in the many genome sequencing projects."
Although all the necessary knowledge is currently available, each step of the three-dimensional analysis is at a different stage in different laboratories. With this major grant, the Commission strives to support the development and the integration of the best technology at each step, and then spread that across all of the sites, according to Victor Lamzin.
Several new European synchrotrons, now on the drawing board or under construction, are scheduled to go on line by 2006 or 2007. BIOXHIT calls for them to begin using the platform from their first day of operations. One immediate effect of BIOXHIT will be a significant reduction in the time involved in obtaining each structure.
Robots, for example, can perform tasks automatically, quickly, and at a consistent and high precision, replacing time-consuming manual steps. The project specifically calls for improvements in the process by which samples are handled, the equipment needed to detect X-ray patterns, and the computers and software needed to model structures. A result of this will be to attract more researchers to work on protein structures.
"Biocrystallography used to be a field for specialists", Victor Lamzin stated, "but today, researchers from all walks of biology want to solve molecular structures at the synchrotrons. The new platform will make this process very user-friendly; it will even allow them to send us their samples and work remotely, from their own institutions."
"This grant from the European Commission will definitely make Europe a substantial player in this area", explained Victor Lamzin. "As well as uniting technologies, BIOXHIT will unite other European and national activities into one strong European alliance, giving us the strength to be a major competitor in structural genomics on a global scale. Similar initiatives are already underway in the United States and Japan, our two main competitors in this area."
Training activities are a cornerstone of the project. A number of Training, Implementation and Dissemination centres will be created outside the participating laboratories to disseminate the know-how. A pro-active training effort will take place at synchrotron facilities, and then be spread to satellite centres to disseminate biocrystallography technologies to local European communities.