One of the grand challenges in biology is to combine structural biology with cell biology so that an atomic level dissection of the cell can be reconstituted into a functional system, including its temporal dimension. The fantastic technological developments of the structural and biochemical methods in the last years make the dream accessible. Structural biology provides detailed mechanistic information about biological macromolecules and complexes that underpins our understanding of biological processes in healthy and diseased cells. It thus has enormous impact on biomedical research as evidenced by recent Nobel prizes awarded for the structure of the ribosome (2009, the major antibiotic target) and the structure of GPCRs (2012, the protein class targeted by ~40% of all current medicinal drugs). Achieving these breakthroughs depended on researchers having access to cutting edge instruments and technics for analysis of biological structures at different resolution ranges, from atomic to cellular, and combining these results in an integrative approach. Instruct, whose overall goal is to promote innovation in biomedical science, was set up to provide open access to cutting edge structural biology, specifically supporting research that uses integrated approaches and technologies. It provides peer-reviewed access for users to a broad integrated palette of state-of-the-art structural biology equipment and know-how, facilities include up to 34 technology subcategories. Instruct supports access with expert staff on-site and training for users of the instrumentation.
History leading up to the formation of Instruct:
Europe followed initiatives in the USA with the setting up of the Protein Structure Factory in Berlin, Germany, the Oxford Protein Production Facility (OPPF) in Oxford, UK and the Genopoles in France. However in October 2002 the first Europe-wide project began with the vision of a few European scientists which led to the formation of a consortium of structural biology laboratories. The project, funded by the EU FP5 programme was called SPINE: Structural Proteomics IN Europe. SPINE, a ‘second generation’ structural proteomics project benefited from the experience and technology development of the preceding projects while taking a more focused approach to target seelction. This was the initiator for a series of structural proteomics projects, funded by the EU which strengthened and expanded the consortium such that ever more challenging targets could be addressed.
SPINE pushed forward with cutting edge technologies aimed at biomedically relevant targets at the same time as generating a pan-European integration on biomedically focussed structural proteomics. Comprising nineteen leading centres in structural biology distributed throughout Europe, SPINE was a resounding success, culminating in a special Issue of Acta Crystallographica Section D (Vol 6(10), 2006) in which the key findings were published. Its successor, Spine2-Complexes, built on the strengths of SPINE and tackled more difficult protein complexes relevant to human health and disease, using the automated and in some cases high throughput technologies developed in SPINE and further expanding these for the more demanding targets.
By the end of the Spine2-Complexes project (2010), this European consortium group had an excellent reputation for delivering and implementing cutting edge technologies in a number of European laboratories, for making these accessible (in collaborative research) to many scientists and by encouraging their adoption into less well developed laboratories, thereby increasing the standard of structural biology across Europe. The foray into difficult targets and the rapid development in 3D imaging which, to that date, had not been explicitly included in the consortium, prompted the next major venture for European structural biology led by this group.
In 2002, the European Strategy Forum for Research Infrastructures (ESFRI) was established, representing the Member States research ministries and the European Commission. ESFRI produced the first Roadmap on Research Infrastructures that defined the mid- and long-term strategy for European Member States in 2006 and the EU provided funds to support the preparatory development of infrastructures in Europe. The European consortium born from SPINE and Spine2-Complexes rose to the challenge of setting up Instruct to deliver access to high-end infrastructures for structural biology to European scientists. The Preparatory Phase of this initiative, generously funded by the EU, enabled the ambitious and sometimes frustrating path towards today’s Instruct to be fashioned from vision to reality. Many of the scientists who foresaw the first SPINE vision are still part of Instruct and many more scientists have since joined the group such that Instruct now has an active following comprising in excess of 700 European scientists. Now at the start of a transitional Operations Phase, the challenge for Instruct has really just begun.
As structural biology now requires integrated approaches combining multiple technologies, Instruct is the single vehicle delivering this truly integrative approach not only in Europe but beyond. Most individual services provided by Instruct Centres are not commercially available in the private sector. Certainly no infrastructure on this level exists in the world that provides the multi-platform, integrated format available to Instruct users. Thus Instruct will be a major player in promoting innovation and discovery in biomedical science, defining a Strategic plan for structural biology in Europe that will help to develop the European Research Area, supporting the biotechnology and pharmaceutical industries and helping to meet the Grand Challenges as defined by Horizon 2020.
To service the scientific and translational mission above, Instruct is a distributed European infrastructure whose task is to provide peer-reviewed open access for users to a broad integrated palette of state-of-the-art structural biology infrastructure, thus promoting innovation in biomedical science and facilitating high impact research. Instruct provides open access to high-end technologies that might not otherwise be available to users through institutional, regional or national facilities. These technologies, chosen to represent the most advanced or specialist, are provided with the experience and expertise to guide users through an experimental process that optimizes the research outcome and provides practical training in parallel. An additional Instruct training programme provides both basic training in structural approaches and methods for the new user, and more specialist training for those wishing to expand their skills.
Importance for European Research
Instruct strategy has been to select as its nodes, complimentary Centres of excellence where advanced structural biology instrumentation and methods are available in an expert academic setting. Instruct offers a single point of access to both multiple techniques integrated at one site or over sites, or to more specialized Centers that have developed unique expertise. This strategy has the advantage that scarce, highly expensive instrumentation combined with the necessary expertise and training capacity, is available for international access and thus promotes dissemination of technical advances throughout Europe. Furthermore, as biology now requires integrated approaches combining multiple technologies, Instruct is the single vehicle delivering this truly integrative approach not only in Europe but beyond. Thus Instruct will be a major player in promoting innovation and discovery in biomedical science, defining a Strategic plan for structural biology in Europe that will help to develop the European Research Area, supporting the biotechnology and pharmaceutical industries and helping to meet the Grand Challenges.
Finally, Instruct is ideally positioned for designing a combined top-down and bottom-up strategy for future investments in structural biology in Europe. The experience accumulated by Instruct is extremely valuable and ideally positions Instruct for describing the future European Infrastructure landscape in structural biology, given the current scientific trends, and with our detailed knowledge of the present situation in Europe. Instruct is initiating these actions to deliver such a strategic view, with added perspective from the Instruct Independent Scientific Advisory Board.
Value of Instruct
Instruct’s uniqueness lies in offering a coordinated route to access each of the Instruct technologies appropriate for the best scientific outcome: this takes the form of peer-reviewed, free-at-the-point-of-use, open access with expert support and supervision with advice on other methods, technologies or approaches that might be useful. Added value is gained by the user in discovering new opportunities for exploiting synergistic integrative approaches through collaboration, mobility to excellent facilities, expert training and increased skills in the latest and developing technologies.