Great public, political and academic excitement has been generated over the last couple of years with the release of several complete genome sequences, with new opportunities for dramatically improving human health and biotechnological processes. The tremendous effort required to get such information now needs to be realised through study of the encoded proteins themselves, many of which are potential therapeutic targets as a result of their intimate role in modulating cell responses, and hence their implication in disease.
All major structural genomics activities worldwide include some protein production activity, usually based on fortuitous successes with a limited number of proteins. However, directed activities to address the problems of protein production for functional and structural analysis are much less well supported or co-ordinated than the genomics and structural activities themselves, despite this being a major limiting factor for many proteins, especially those in complexes and hydrophobic proteins. The EUROCORES programme EuroSCOPE bridges this gap for scientific collaboration and innovation, in which is generally not foreseen through funding at the national or EU (FP6) level.
The importance of transferring successes, openly discussing and learning from mistakes, to then focus on developing new technologies in collaborative research projects, is an ideal Community activity where accumulated knowledge is vital – this activity does not formally go on at present.
The scientific goals
This programme intends to tackle the major stumbling blocks in the production of proteins for functional and structural analysis. The focus will be on the basic understanding of the mechanisms underlying protein production, targeting, folding and stability, which eventually may result in the improvement of existing and the design of new expression systems. The work should lead to a firm foundation for the rational engineering of strains for the production of complex proteins such as multi-domain eukaryotic proteins, integral membrane proteins and multi-enzyme complexes. Thus far, these complex systems are highly underrepresented in the protein structure databases, because they are difficult to overproduce in a functional form and in amounts suitable for functional and structural work.
The emphasis in the Phase I of the programme is on the science of all aspects of protein production to permit structural studies of complex systems to begin. The program will not fund projects that aim at scaling up of the processes or the setting up of protein factories for the production on demand, although such initiatives will benefit from basic knowledge of protein production as proposed here. In Phase II of the programme, the structural analysis of the complex protein systems will become more prominent as this is evidently the second major hurdle in the exploitation of the wealth of genomic information currently available.
Detailed scientific description of the EuroSCOPE programme
The aim of this EUROCORES programme is to provide a mechanism through which to generate a basic understanding of every aspect of the Science of Protein Production where proteins are required for structural and functional analysis. Protein production can be used to address a wide range of requirements, and these can be classified into a variety of tasks arranged into sub-fields, often driven by the final goal of the study. These sub-fields can therefore provide a focus for collaborative research projects from applicants, either where current expertise is already at a high level, or where expertise could be developed. Detailed descriptions of sub-fields
What is wanted from applicants
It is the science of protein production and the development of tools for structural and functional analysis using genetic and biochemical methods which is being supported. Ways of resolving difficulties and problems presented by the area should be explored, with the aim of reliably transferring skills and “know how” and developing generic methods where possible.
High risk, innovative and forward looking proposals are encouraged, designed to solve major bottlenecks as identified here, or identified separately by applicants. Some back up to cover situations where goals may not be fully reached, are required. It is expected that these collaborative research projects will build on a base of activity and expertise, rather than be generated from a “zero base” level of activity.
Networking alone is not sufficient, and plans for real collaborative project development involving other groups, post-doctoral and technical effort commensurate with national eligibility rules, (see “Guidelines for proposals”) is essential.
All applicants will be encouraged to suggest how they will engage in one or more activities designed to disseminate information, such as a willingness to organize workshops, hold training courses, and develop means of storing and disseminating information widely and freely to the benefit of the whole community.
Future plans
It is anticipated that some progress will be made and productive collaborative projects established within 1 – 3 years. The next phase of the EUROCORES, however, will clearly be the use and exploitation of the systems being produced. It is therefore fully anticipated that in some highly productive areas of protein production, where bottleneck have been resolved, whether through this EUROCORES or not, that a structural and functional investigation phase will be initiated. The timing of this Phase II call for proposals and their management will be reviewed within 2 - 3 years of the current EUROCORES commencement.
