We propose to build on the success of the European Yeast Genome Sequencing Network (EYGSN) by establishing a new Network which aims to elucidate the biological function of 1,000 novel Saccharomyces cerevisiae genes discovered during the Sequencing Project. EUROFAN is constructed in an hierarchical manner which permits us to approach the biological function of a particular gene with ever-increasing specificity as it moves down the pathway of analysis. This structure is efficient since not all of the analyses need be performed on every gene. Systematic functional analysis is not intended to replace 'normal' biological research. Rather, we aim to take the analysis of each novel gene to a level at which a specialist laboratory can, with confidence, incorporate it into its own research programme. Thus EUROFAN plans to accelerate the progress of 'normal' research by creating an informational and a material resource which is both without current parallel and of enormous utility to biomedical science and the bio industry in Europe. This resource will take the form of: (i) a large object-oriented database of gene function, and (ii) a genetic archive and stock centre comprising yeast strains containing specific deletion mutations and plasmids containing the individual genes as well as disruption cassettes allowing their manipulation in any laboratory or industrial yeast. EUROFAN will be a large transnational Network involving a total of 145 laboratories from 14 European nations. These labs. are in Universities, Research Institutes and both large and small Industrial Enterprises. The commercial utility of EUROFAN's output will be constantly reviewed by the Yea-st Industry Platform (YIP) to ensure that the competitiveness of European Industry is enhanced through rapid and efficient technology transfer. The output of individual labs. will be quantifiable and the principle of 'payment-on results', pioneered by EYGSN, is retained. Thus EUROFAN, like its predecessor, will represent an integrated EU- wide collaboration dedicated to the efficient pursuit of pre-competitive research for the common good of European bioscience and the industries which it supports.
The research programme is organized in an hierarchy which has two principal levels. There are two sets of Resource Consortia. The first set provides service or material resources which will be required by the whole of EUROFAN: A. Services: Al. Central coordination. Includes administration of 'payment-on results'. A2. Informatics. (i) repository for data with quality control procedures for 'payment-on-results'; (ii) creation of the object- oriented database; (iii) development of new computational tools to enable intelligent utilization of the data. A3. Industrial Liaison lYlP. Commercial evaluation and technology transfer. A4.Genetic Archive & Stock Centre. Repositories and distribution centres for the 1,000 specific deletants and their cognate gene clones, disruption cassettes and primers. This material will be available for all EUROFAN researchers and will form the basis of a permanent European Collection. The second set of Resource Consortia will comprise the first level of our function search hierarchy, permitting approximate assignments that allow individual genes to be passed to the next, and more specific, level. B. Basic, Fundamental Analyses: B0. Generation of deletants and corresponding plasmid tools. All EUROFAN labs. with a molecular biology capability will participate in creating this resource, working to prescribed protocols and verified standards.
Bl. Qualitative phenotypic analysis. B2. RNA-level expression analysis. B3. Protein-level expression analysis (PLEA) I: 2-D protein gels. B4. PLEA II: gene fusions. B5. Gene interactions: 2-hybrid analyses.
B6. Quantitative phenotypic/ Metabolic control analyses. B7. Sub-cellular structure & organelles. B7 Relation to other genomes. B8. Novel methods of genome analysis. From these Resource Consortia, sub-sets of genes will be passed, for more detailed analysis, to specific Function Analysis Nodes: IN.DN synthesis/ cell cycle. 4RN processing. N3.Translation. N4.Stress responses. N5.Cell wall synthesis/ morphogenesis. N6.Transport. N7.Energy/ carbohydrate metabolism. N8.Lipid metabolism. N9. Special Metabolism. N10. Development. N11. Recombination/ repair/ mutagenesis. N12. Chromosome structure & function. N13. Cell architecture. N14 Secretion and protein trafficking.
This structure should allow efficient identification of pleiotropic genes, the distinction of primary from secondary effects and the indication of entirely new biological functions.